The funding level for this activity in FY 2008 has increased since FY 2007. Narrative changes include

updates on progress made and expansion of activities. Two PHE's have been removed from this activity per

OGAC guidance and appear as separate activities.

This activity links with other PMTCT programs with WPHO, EPHO, and CARE International.

The Center for Infectious Disease Research in Zambia (CIDRZ), under the prime partner Elizabeth Glaser

Pediatric AIDS Foundation (EGPAF), will continue to expand the prevention of mother to child transmission

of HIV (PMTCT) implementation program in collaboration with the Ministry of Health (MOH). There are also

two public health evaluations (PHEs) included under this activity. In FY 2008, CIDRZ in partnership with the

Government of the Republic Zambia will focus on:

1) Providing PMTCT services to 80% of the health centers in Lusaka, Western, and Eastern Provinces

where feasible.

2) 100% of the health centers in Lusaka and 75% in other supported sites offering more effective

PMTCT interventions Nevirapine (NVP)-boosted Zidovudine (ZDV).

3) Improving links to care and treatment by implementing highly active antiretroviral therapy (HAART)

for pregnant women within maternal and child health (MCH) clinics at selected sites in Lusaka.

5) Scaling-up early infant diagnosis at six weeks using virological testing to all district capitals

supported by CIDRZ.

4) Implementing and improving upon performance based funding to districts to promote sustainability.

5) Support the most efficacious PMTCT regimens to all pregnant women with CD4 counts less than

350 at the University Teaching Hospital (UTH) and two Lusaka District facilities.

By working directly with the MOH, Provincial Health Offices, and districts, CIDRZ plans to considerably

expand the number of health centers providing PMTCT, from 201 by the end of February 2008 to 250 by the

end of February 2009. Therefore the overall PMTCT coverage will be 80% of the health facilities and

districts within three provinces of Zambia. Sustainability of the PMTCT program will be achieved through

the integration of PMTCT services into routine MCH activities.

CIDRZ is transitioning towards a system where funding is given directly to the districts to implement safe

motherhood and PMTCT services with a goal of developing a sustainable model. In this model, districts are

given seed money to start of PMTCT services at clinics which are not providing PMTCT services. These

funds can be used to orient stakeholders; buy necessary supplies; or other things to promote PMTCT.

Districts are also given money for individual clinics to support PMTCT based on the actual numbers of

pregnant HIV infected women who are counseled and tested for HIV and who receive ART on a monthly

basis. CIDRZ has signed an MOU with each district outlining guidelines for how the individual clinic money

can spent. A breakdown of items on which the money can be spent has been agreed upon and includes:

community activities; back-up supplies; support for lay counselors or staff within the clinics. On a quarterly

basis, CIDRZ will meet with the districts to review the terms of the agreement and review the performance

of the individual clinics as well as the district oversight of the safe motherhood and PMTCT programs

The mother-infant rapid intervention at labor and delivery (MIRIAD) intervention was continued and

expanded to seven clinics in Lusaka at the end of May 2007. By mid 2008, all clinics in Lusaka, as well as,

major district health centers will implement testing in labor as per the national PMTCT guidelines. CIDRZ

will continue to support districts to develop networks and referral systems for pregnant women and HIV-

exposed infants to access other services offered at health centers and in the communities. This would

include the development and strengthening of the existing sample referral system. For example, CD4 and

dried blood spot samples are taken from feeder clinics and sent to larger facilities for laboratory processing

and then the results are returned to feeder clinics.

A key activity will be referrals to HIV care and treatment programs, including screening of women for a CD4

count to determine eligibility for antiretroviral therapy. In FY 2008, the program will go a step further to

implement the provision of ART to eligible pregnant women until six weeks postpartum in selected MCH

clinics with an overall goal to improve links to care and treatment and to dramatically reduce the incidence

of pediatric HIV. At the UTH, the program will support the implementation of a "Center of Excellence in

PMTCT" at the Adult Infectious Disease Center, located just next to the Geriatrics Department. This unit will

focus on implementation of the most efficacious PMTCT regimens which are currently available to women

who are eligible for HAART based on the most conservative interpretation of the WHO guidelines (all

pregnant women with CD4 counts <350 or Stage IV) . This clinic will also provide the highest standard of

care with regard to the availability of all relevant lab tests including liver function tests, full blood counts, and

viral load as deemed necessary. When the results of the Kesho Bora study are released, we will consider

giving all pregnant women HAART regardless of CD4 count or clinical stage. A multidisciplinary approach

to the care of pregnant women including consultation and coordination with physicians at the center will be

employed.

Currently, all 24 clinics in Lusaka offer early infant diagnosis of HIV. The EGPAF-CIDRZ program aims to

test 60% of all infants delivered to HIV-infected mothers in Lusaka at six weeks of age using polymerase

chain reaction (PCR). HIV-infected infants will be referred for continued care and treatment. To increase

numbers of infants below 18 months tested in MCH, the program will train health care providers and

auxiliary staff to identify HIV-exposed infants and infants suspected of HIV infection. In collaboration with

the ART program, PMTCT will support the implementation of routine counseling and testing of infants and

their parents in hospitalized children and in outpatients' clinics.

EGPAF-CIDRZ will continue to work with CDC to implement the SmartCare system, which will facilitate

improved longitudinal care for pregnant women and their infants. Health workers will be trained in

counseling, the minimum package of care of PMTCT, logistics, data management, and quality assurance as

new and ongoing activities in these districts. Through implementation of the fixed cost obligation model,

EGPAF-CIDRZ will support district staff retention and support of auxiliary staff in a bid to address the

Activity Narrative: shortage of staff in MCH departments. To support scale-up of PMTCT in rural areas, CIDRZ has adapted

the traditional birth attendant (TBA) manual and has trained and will continue to TBAs to improve PMTCT

service delivery in rural settings. As part of this program, EGPAF-CIDRZ will raise community awareness

for the PMTCT program through the development of materials and information, education, and

communication strategies. The communities, especially men, will be mobilized and encouraged to

participate in the PMTCT community outreach programs that promote HIV testing in order for the program

to be effective. Finally, CIDRZ will continue to bring two volunteers for one year to support PMTCT

expansion, to provide technical assistance, promote knowledge transfer, and provide creative solutions to

problems.

The targets set below are to be achieved by September 30, 2009.

Title of Study: PMTCT Program Effectiveness

Time and Money Summary: This Study started in FY2007 with a budget of $358,000 and the budget for FY

2008 will be $189,000.

Local Co-Investigator: Drs. Elizabeth Stringer, Benjamin Chi and Jeffrey Stringer are Co Principal

Investigators. Dr. Namwinga Chintu is an Investigator.

Project Description:

In this PHE, we will measure PMTCT program effectiveness in designated, Emergency Plan-sponsored

districts using a community-based survey methodology. The proposed method will measure population HIV-

free survival in the general population of children and among HIV-exposed infants and is designed to

minimize biases and provide a population-based estimate. Given the large investments in PMTCT programs

both by the Zambian government, the USG, and other donor agencies, development of a standard and

reliable measure of PMTCT effectiveness is an urgently needed component for the continued optimization

of services and resources.

Evaluation Question:

Direct measurement of PMTCT program effectiveness in the field has proven challenging in resource-

limited settings such as Zambia. Early infant HIV diagnosis generally requires nucleic-acid-based (PCR) or

ultrasensitive p24 assays, neither of which are feasible in many settings outside Lusaka owing to their

expense and technical complexity. Later diagnosis with rapid antibody testing after the cessation of

breastfeeding can be done almost anywhere, but when used as a program evaluation tool, it is hindered by

the persistence of maternal antibodies for 15-18 months, and suffers from ascertainment bias; babies who

die do not return for diagnosis, thus causing an overestimation of program benefit.

Because of these challenges, Zambian decision-makers rely primarily upon collection of various process

indicators to measure program success. Many of these indicators are critical steps along the pathway to

PMTCT service "coverage," such as the proportions of women offered testing, accepting testing, receiving a

prophylactic intervention, etc. A danger of relying exclusively upon process indicators, rather than directly

measured outcomes to assess program effectiveness, is that the process indicator approach has never

been validated as a reliable surrogate for effectiveness, and may substantially overestimate it.

The primary focus of this monitoring activity will be to measure directly the gold standard metric of childhood

HIV-free survival in selected populations. We propose the development and implementation of community-

based monitoring within a variety of communities within Zambia. If validated through our activities, we

believe this methodology could have a significant impact on how programs are assessed in settings like

ours.

Methodology:

We will employ a community survey methodology that seeks out households with a child less than 2 years

of age (who may be alive or deceased). Monitoring activities will consist of 2 parts. First, a questionnaire will

be completed regarding patient and family demographics, health care service utilization (including ART and

PMTCT), and HIV/AIDS knowledge and attitudes. In addition, we will obtain specimens for anonymous,

unlinked testing: a venous specimen or oral swab from the mother and children > 2 years, and dried blood

spot (via heel-stick) for children 2 years or less (and any who are still breastfeeding). In households where

surveyors identify a birth in the prior 5 years where the mother has died, verbal autopsy interviews will be

performed to approximate the cause of death. In these cases (estimated ~ 10% from our experience in

Lusaka) the possibility of an AIDS-related maternal death can be estimated via verbal autopsy interviews

with family members.

Maternal specimens will be analyzed for maternal HIV antibody status, and, depending upon funding

availability, recent infection through the use of "detuned" assays (this latter issue is of particular interest

among those who are still breastfeeding). Child specimens will be analyzed for HIV antibody status.

Together, these data will allow direct measurement in the population of 1) early and late infection rates

among exposed infants; 2) infant, child, and under-5 mortality among all children, with stratification by HIV

exposure status; 3) HIV-free survival in the general population and among those exposed to HIV. The

precision of the survey's estimate will be directly linked to the available sample size, which in turn, hinges

on the budget. We are proposing a sample size that is adequate to estimate population HIV-free survival

rates among HIV-exposed infants within a 5% margin of error.

Status of Study/Progress to Date:

This study is part of a larger multi-country study which includes Cote d'Ivoire, South Africa and Cameroon.

The contract was awarded to UAB/CIDRZ in September 2006. The protocols for this multi-country study

were submitted to the CDC in February and March 2007 and are currently under review at the IRB of the

CDC. The implementation of this PMTCT Effectiveness study in Zambia will begin as soon as IRB approval

is granted by the CDC. IRB approval has already been granted by the ethics committees of UNZA and

UAB.

UAB has now prepared and signed off on the contracts for the cost effectiveness evaluation which will be

done as part of this larger study. We will begin with data collection as soon as IRB approval is granted.

Population of Interest:

Unlike previous work, we propose a community-based (vs. a facility-based) approach to determining

PMTCT program effectiveness. As such, households in each community will be sampled within designated

census enumeration areas in a random fashion, using demographers from the University of Zambia and a

methodology already developed by CDC/CIDRZ for the Lusaka District Community Health Survey.

Budget Justification:

Requested budget will include personnel (including study leader, operations coordinator, data entry clerks,

data manager and analysts), administrative costs, survey/field work (to be subcontracted to a group at the

University of Zambia), laboratory supplies and reagents. No incentives are provided for participants.

Salaries/fringe benefits: $115,000

Equipment: $0

Activity Narrative: Supplies: $0

Travel: $0

Participant Incentives: $0

Laboratory Testing: $15,000

Other: $59,000

Total: $189,000

April 08 Reporgramming: Prime Partner: Elizabeth Glazer Pediatric AIDS Foundation, Agency: CDC,

Funding Mech: HQ

Title of Study: Elizabeth Glazer Pediatric AIDS Foundation Antiretroviral Pregnancy Registry, a Multi-

Country Study.

Time and Money Summary: This Study started in FY2007 and $277,500 from the EGPAF Carryover

Budget will be spent. It is anticipated that this activity will need $275,000 from FY2008. This will be a three

year study.

Local Co-Investigator: Dr. Wm. Perry Killam, CIDRZ-UAB, Zambian Project Coordinator and Dr.

Bushimbwa Tambatamba/LDHMT/MOH; Co-Investigator

Project Description:

In this PHE, we will establish a multi-country voluntary registry of women exposed to antiretroviral therapy

(ART) during pregnancy and perform observational surveillance on HIV - positive pregnant women who are

exposed to antiretroviral medications during the prenatal period, in order to evaluate the safety of the

medications in pregnant women and their infants.

Evaluation Question:

Combination ART delays disease progression and HIV-infected pregnant women are increasingly treated

with highly active ART both for their own health and to reduce vertical transmission. Although the use of

ART in pregnancy has significantly reduced rates of vertical transmission of HIV-1, some questions remain

regarding the safety of these therapies and their potential impact on the infant. The goal of the Antiretroviral

Pregnancy Registry is to perform observational surveillance on HIV - positive pregnant women who are

exposed to antiretroviral products during the prenatal period in order to evaluate the outcome of the

pregnancy and safety of the medications. In particular, the registry will evaluate exposure to ART during the

beginning of pregnancy and document the frequency of adverse events including birth defects among

infants or fetuses born to mothers exposed to antiretroviral treatment during pregnancy.

Programmatic Importance:

Given the large number of reproductive age women on ART and increasing use of ART during pregnancy,

development of a pregnancy registry is a needed component for safe use of ART by determining the

potential impact on pregnancy outcome. The results of this targeted evaluation will be used to supplement

other human and animal studies in understanding the safety of ART used during pregnancy. It will assist

clinicians caring for HIV-infected pregnant women in the management of her ART care.

Status of Study/Progress to Date:

The Protocol has been developed and submitted to the local IRB at the University of Zambia Research

Ethics committee and the University of Alabama at Birmingham Institutional Review board. The Operations

Manual has been drafted, study nurses interviewed and a PHE Meeting is planned for September 2007.

Methodology:

We will establish a multi-country voluntary registry of women exposed to antiretroviral therapy (ART) during

pregnancy and perform observational surveillance on HIV - positive pregnant women who are exposed to

antiretroviral medications during the prenatal period. The Registry will be fielded in Zambia and Ivory Coast

in two phases. Phase I of the study is expected to begin in September 2007 and will expect to enroll 500

women prospectively over a 6 month period between the two participating countries. As well, a

retrospective arm of Phase I will examine reported outcomes of pregnancy from eligible women who

delivered in the past 6 months prior to initiation of the prospective arm. This retrospective analysis will be a

review of the existing medical record information from Smartcare and ZEPRS electronic databases. Phase

II of the study is expected to enroll 1000-1500 participants starting in 2008 and will contain a comparison

population. In Zambia, potential participants will be identified through review of the SmartCare and Zambia

Electronic Perinatal Records System (ZEPRS) electronic databases, which containing routinely collected

information on patients' clinical care visits for Care and Treatment and pregnancy care. The patients' ART

regimen and pregnancy status are routinely assessed in the ART clinic, written on standardized forms and

entered into the SmartCare electronic database. The pregnancy status, HIV status and ART medication

status are routinely collected during antenatal care in the ZEPRS system. Women fulfilling the inclusion

criteria on review of the electronic databases will be considered potential participants and will be asked to

enroll voluntarily in the Registry. The data gathered will allow for determination of the frequency and

distribution adverse events by gestational age at exposure and by various drug regimens being used in

resource-limited countries.

Population of Interest:

The population of interest is HIV infected women who are on combination ART then become pregnant. In

Zambia, the population will be HIV infected pregnant women on ART attending one of the public health ART

clinics in Lusaka District.

Information Dissemination Plan:

It is intended that the results of this EGPAF APR will be published in a peer-reviewed journal with the aim of

submitting a paper for publication within six months of EGPAF APR completion. The initial manuscript

describing the multi-country results will be created by the Principal Investigator and distributed to study

investigators and site staff for input and comments. A final EGPAF APR report will be prepared in

collaboration with all Clinical investigators. This report will be provided to all investigators who contributed to

the EGPAF APR and the IEC/IRB if required.

Budget Justification:

Activity Narrative: Requested budget will include personnel (data entry clerks, data analyst), contractual cost for modifying the

data gathering electronic database and administrative costs. A detailed budget is available upon request or

can be found in our pending application to the CDC under EGPAF Project HEART carryover. No incentives

are provided for participants.

Salaries/fringe benefits: $155,000

Equipment: $2,500

Supplies: $3,000

Travel: $4,500

Participant Incentives: $0

Laboratory Testing: $0

Other: $110,000

Total: $275,000

Title of study: Evaluation of safety and acceptability of neonatal circumcision in Zambia using Gomco and

Plastibell methods

Time and money summary: 1 year

Local Co-investigator: Dr. E Stringer, CIDRZ, Dr. Chipepo Kankasa, UTH and a Paediatric MMED student,

TBN.

Project description: Three recent studies in Africa have shown that male circumcision reduced acquisition of

HIV in men. No studies have been done on neonatal male infants, but we can infer from the recent trials

that circumcision at birth would have many health benefits including decreased acquisition of HIV. Infant

circumcision is routinely performed in the United States without complications, but is not widely done in

Africa. Its safety and acceptability has not been formally evaluated in Zambia, specifically. We will evaluate

the safety and acceptability of two techniques of neonatal circumcision in a variety of different settings

around Zambia.

Neonatal circumcision has an estimated complication rate ranging from 0.1% to 35%. [American Academy

of Pediatrics] The majority of complications relate to infection or bleeding. Meatitis and meatal stenosis can

also occur. The Gomco technique employs a reusable surgical instrument but requires more surgical skill to

avoid bleeding complications. With the Plastibell technique, the plastic bell that is used to demarcate the

surgical incision is left in place for up to a week following the procedure. There is believed to be less

bleeding complications with this technique - especially in a setting where doctors may not be performing the

procedure - but the foreign body at the surgical site may predispose to infection.

Evaluation questions: 1) Evaluate the safety of neonatal circumcision in Lusaka, Chipata, and Kafue. 2)

Describe baseline minor and major complications 3) Evaluate the acceptability among providers and

patients of neonatal circumcision

Programmatic importance/anticipated outcomes: As neonatal circumcision becomes one component of

Zambia's plan to prevent HIV, it is important to understand the safest and most acceptable techniques to

use; the most appropriate people to train in the procedure; as well as the best ways to educate both

providers and communities. We hypothesize that the Gomco method is the safest and most acceptable,

however, this has not been the case in the United States. The information gained will inform scale up

measures of neonatal circumcision.

Methods: Over this one year period, we will circumcise 1400 infants, alternating between Gomco and

Plastibell each week (i.e. week 1 Gomco, week 2 Plastibelle, week 3 Gomco, etc). Infants will be followed

up at one week, one month, and three months. We will evaluate rates of bleeding at the time of the

procedure and subsequently, and rates of infection at each follow-up visit. We will also evaluate infants for

evidence of Meatitis and meatal stenosis. We will also collect information on the type of provider trained and

location; provider experience (i.e. number of circumcisions he or she has performed), and individual infant

characteristics. We will categorize any complication as major or minor. In addition to the evaluating the

safety of neonatal circumcision, we will develop questionnaires which will be used to capture the best

methods of training; providers' attitudes towards neonatal circumcision; parent's attitudes towards neonatal

circumcision; and communities attitudes towards neonatal circumcision.

The primary outcome will be the proportions of infants experiencing any complication among circumcisions

performed with a Plastibell vs. Gomco. Our proposed sample size will allow us to distinguish between a 1%

complication rate in the Gomco group versus a 3% complication rate in the Plastibell group (80% power,

alpha = 0.05, not correcting for clustering effect of the week-by-week randomization).

Population of interest: The population of interest would be healthy full term male infants born within 24-48

hours determined to be good candidates for circumcision and weighing no less than 2500gm. Parents will

be identified while still pregnant and educated on the pros and cons of neonatal circumcision.

Information Dissemination Plan: The information gained from this evaluation will be presented to the

Ministry of Health and disseminated in each area in which the evaluation took place.

Budget justification for Year 1 budget (please use US Dollars):

Salaries/fringe benefits: $55,000

Equipment: $20,000

Supplies: $30,000

Travel: $20,000

Participant Incentives: Follow up $15,000

Laboratory testing: $0

Other: $115,000

Total: $255,000

The following activity is newly proposed ¬for FY 2008. This is to capture the ARV Services patients that are

receiving palliative care services.

This activity links with the Zambia Prevention, Care, and Treatment Partnership, PMTCT, AR, Counseling

and Testing (CT), Tuberculosis (TB)/HIV, and Laboratory Support activities as well as with the Government

of the Republic of Zambia (GRZ) and other US Government (USG) partners.

Though Project Help Expand Anti-Retroviral Therapy for Children & Families (HEART) is primarily a

provider of ART services, it provides services in treatment of opportunistic infections (OI) including TB,

sexually transmitted infections (STI), as well as pain and symptom management, and clinical care for

severe malnutrition. This represents 30-40% of the clinical care provided to people living with HIV/AIDS

(PLWHA) at ART sites. The ART training package includes training on OI management, cotrimoxazole

prophylaxis, STI, and TB screening.

Because of the role of STI in HIV transmission it was felt that a more targeted approach would be beneficial

in this high risk population. Center for Infectious Disease Research in Zambia (CIDRZ) in collaboration with

the Lusaka District is piloting a targeted program to strengthen STI diagnosis and treatment and has trained

40 people to date. The program focuses on integrating comprehensive STI training packages into general

ART care and training targets all health care providers. Specific TB training and guidelines have been

developed to increase screening and improve the diagnosis of TB in HIV-infected patients.

In collaboration and support from the World Food Program (WFP) and Project Concern International, a US

non governmental organization, patients enrolling into the home based care program are assessed for

evidence of malnutrition and food insecurity. Those found to be food insecure are eligible to receive monthly

WFP food rations (food aid commodities provided largely by Food for Peace) distributed from the ART

clinic. Severely malnourished patients are eligible for PEPFAR funded food and nutritional support, and will

be referred to any such programs operating in the area. Patients with severe malnutrition are nutritionally

rehabilitated and provided with psychosocial support through home based care programs. These services

will be extended to Livingstone by February 2008 and to four more provincial sites by February 2009

depending on continued WFP support to food insecure patients. Negotiations are on going with WFP for

expansion and continued support. Project HEART will support up to 68 clinics in 22 districts.

Project Heart is on target to enroll 78,000 clients on ART and over 125,000 people into the care program by

end of FY 2007 at 54 sites in 22 districts and provides clinical palliative care services through these sites. In

FY 2007, Project HEART trained 420 health professionals in ART/OI/STI/Pain management through full and

refresher courses.

One-hundred and sixty five nurses were trained in diagnostic counseling and testing. This was part of a

new patient triage system where all TB patients are offered HIV testing at enrollment in TB treatment and

those testing positive for HIV are referred to ART services. Seventy-two health care workers were trained in

TB/HIV co-management. One-hundred and twelve health care workers will be trained in TB/HIV patient

flow, monitoring and integration. This training focuses on outlining the interaction between HIV and TB,

clinical presentation, and treatment of co infected patients. In addition, clinical care systems to integrate

TB/HIV care at the clinic level are discussed with participants.

Twenty health care workers will be trained in advanced pediatric care to help them recognize and cope with

the special clinical and palliative needs of pediatric patients. Didactic sessions will be supplemented by

interactive relevant case studies highlighting advances in pediatric care. The case studies will integrate

preventive and curative aspects of care in Zambia.

Fifteen health care workers will be trained in Women's Health with focus on screening and treating cervical

cancer. The training will cover; the anatomy and physiology of the cervix, natural history of cervical cancer,

differentiation between normal and abnormal cervix, visual inspection of cervix with acetic acid and digital

cervicography, and use of cryosurgery as a safe and effective method of treating cervical cancer precursors

in the outpatient setting.

Forty health care workers will learn about STI/HIV syndromic management. This includes assessment of

patients at risk for STI especially as a tool for the prevention of HIV transmission. The training focuses on

the signs and symptoms of both bacterial and viral STI, syndromic treatment, contact tracing, and

prevention. The recognition of herpes simplex type 2 is reviewed including the provision of suppressive

therapy as needed.

In FY 2008, Project HEART will train 200 Health professionals in initial ART/OI management and 120 in the

refresher ART/OI course. In addition, Project HEART will continue to provide regular quality assurance and

improvement assessments. These are presently being done by CIDRZ teams in collaboration with local

and Provincial Health staff. In 2008, this will be done mainly by district and provincial teams with limited

guidance and assistance from CIDRZ staff.

In FY 2008, up to 120,000 clients will receive clinical palliative care services at 68 sites in 22 districts in

Eastern, Southern, Lusaka, and Western provinces of Zambia. Project HEART will consolidate on FY 2007

efforts by providing technical support to ensure quality services and build capacity to manage clinical

palliative care services. There will be training in HIV Triage and master training. The first is a three-day

didactic training and a one day practical course that comprises lectures, case studies and interactive

activities. In practical sessions participants practice taking patient histories, physical examinations,

assessments and patient management. The master training consists of a four-day didactic and practical

training, followed by two weeks of clinical mentoring.

Clinical palliative care activities will include; 1) strengthening palliative care services in health facilities; 2)

increasing referral linkages within and between ART facilities, community HBC, and hospice care; 3)

participating in and assisting the Ministry of Health (MOH) and the National AIDS Council to develop a

strategy, guidelines, and standard operating procedures for provision of quality clinical palliative care in ART

sites; and 4) increasing program sustainability with the GRZ. In the first component, Project HEART will

continue to support up to 68 ART facilities in 22 districts. In addition to the ART/OI/STI/TB training

mentioned above, health professionals will also be trained, using GRZ-approved curriculum, to provide

cotrimoxazole prophylaxis, assess and manage pain. Patient and family education and counseling,

Activity Narrative: management of adult and pediatric HIV in the home setting, and provision of basic nursing services in clinic

settings as part of the overall package of clinical palliative care services will be covered. Pharmacy staff will

be trained in data collection/reporting and ordering, tracking, and forecasting HIV-related commodities to

ensure availability of critical medical supplies and drugs. Project HEART will also work closely with the

USAID/Deliver Project (#9520) and Partnership for Supply Chain Management Systems (#9196) on

forecasting drug supply requirements.

In the second component, Project HEART will build on Zambia's long history of working with Faith-Based

Organizations (FBO) and Community-Based Organizations that provide home-based care for PLWHA.

These organizations serve as critical partners for facility-based programs supported by GRZ and USG.

Therefore, Project HEART will work closely with these established entities to strengthen referral networks

linking clinical palliative care services with community-based programs. CIDRZ will continue to link with

Catholic Relief Services and other local FBO for referral of enrolled patients to more comprehensive home

based care programs.

In the third component, project HEART will continue its participation in and provision of assistance to the

USG Palliative Care Forum as well as coordinate with the Palliative Care Association of Zambia to develop

a national palliative care strategy, guidelines, and standard operating procedures. Through these efforts,

Project HEART aims to improve access to quality clinical palliative care services, promote use of evidence-

based practices, share lessons learned in project implementation, and support the revision of national

palliative care guidelines and protocols in accordance with GRZ policies.

In the final component, project HEART will work with the monitoring and evaluation technical working group

and the care and treatment technical working group to build on the quality assurance activities started in FY

2006. In FY 2008, in collaboration with the GRZ, project HEART will work with district and provincial health

offices to increase numbers of staff on their teams and to increase capacity of staff to assume responsibility

for various program components (lab, pharmacy, quality assurance/quality control, data, clinical care,

community etc). In conjunction with MOH, timelines for capacity building, partial and then complete

transition of program responsibility will be agreed upon.

Different models will apply for rural versus urban settings. The CIDRZ provincial teams will initiate a new

model of scale-up such that new rural sites will be implemented by district offices with oversight and

technical assistance by CIDRZ. Provincial offices will also include timelines and plans to transition program

responsibility to MOH.

Title of Study: Community Impact of HIV/AIDS Services

Time and money Summary: Study Year 4; Started in FY05 and expected to be completed in FY09;

$165,000 will be spent from FY07 and $140,000 is needed for FY08

Local Co-investigator: Dr Jeffrey Stringer of Centers for Infectious Diseases Research in Zambia (CIRDZ)

and University of Alabama at Birmingham (UAB) is the Principal Investigator. Dr T. Kusanthan of University

of Zambia is the local Co-Investigator.

Project description:

In April of 2004, the Zambian Government initiated the antiretroviral therapy (ART) services in Lusaka

beginning in four clinics and expanding to other community health centers over time. This program is

expected to lead to a reduction in community specific mortality and morbidity, particularly as it relates to HIV

and tuberculosis among those receiving treatment. The availability of life-saving ART may also result in a

reduction in stigma and misconceptions regarding HIV/AIDS and its treatment. The Community Impact of

HIV/AIDS Services study is designed to measure the impact of ART services in Lusaka communities.

This study is a repeated cross-sectional complex sample survey that has been conducted in parallel with

program expansion. It is designed to measure changes in the following measures: 1) community mortality

rates (total, infant and child); 2) community morbidity (hospitalizations and incidence of malaria and TB); 3)

knowledge and attitudes towards HIV/AIDS particularly as it relates to stigma; 4) perceptions and

acceptability of HIV testing; and 5) knowledge and attitudes related to antiretroviral drugs.

Each cross-sectional survey provides estimates of the above outcomes within the individual constituent

communities as well as Lusaka generally. The specific aim is to relate the advent of ART services in local

health centers to changes in the respective community level outcomes. Changes attributable to ART

services are evaluated by observing changes within a community, before and after the advent of local ART

services as well as differences between communities with and without ART services at any given time.

Furthermore, the surveys will assist in identifying potential barriers working against community outreach,

HIV counseling and testing services and other community based interventions.

Each is a sample survey of the catchment areas for all district government clinics. Each survey round is

conducted over a period of three weeks in 150 households in the catchment areas for each of 24 district

clinics in Lusaka for a total of 3,600 households. The respondent is the male or female head of household

who responds to questions about herself and those living in the household. A list of Standard Enumeration

Areas (SEAs) and the nested Census Enumeration Areas (CSAs) representing the catchment areas for

each of the local health clinics was provided by the Central Statistical Office of Zambia. At each round three

CSAs for each catchment areas are randomly selected. 50 households in each CSA are surveyed at fixed

intervals inversely proportionate to the number households in each CSA, beginning with a randomly

selected household at the center of the CSA. The survey is conducted by a team of 16 interviewers and 4

supervisors. The questionnaire used in the survey is administered in English or either Bemba or Nyanja (the

two most widely spoken dialects). The administration of the survey is sub-contracted to a University of

Zambia based investigator.

Analysis of these data will be performed using Proc Mixed and Proc Genmod in SAS (Version 9, Carey NC)

to account for the variance dependencies in the survey due to the similarities of persons living within the

same communities.

Status of study/Progress to Date:

The seventh round of the survey is currently underway. Analyses are currently underway to relate mortality

and morbidity changes to the timing of ART initiation in the community clinics. The continued community

surveys will provide more data for the before and after as well as the between community comparisons from

which the mortality changes attributable to ART can be made.

Lessons Learned:

Preliminary analyses have demonstrated a marked reduction in mortality between the first and the second

community survey. However, much of this reduction may be due to the occurrence of an outbreak of

Cholera which occurred just prior to the initiation of ART services.

Information Dissemination Plan:

The study results will be disseminated through in Country dissemination meetings, abstract presentation at

local and international conferences and publication in peer reviewed journals.

Planned FY08 activities:

We plan on continuing four rounds of the surveys which should coincide with the culmination of ART service

expansion activities in Lusaka.

Budget Justification for FY08 monies (please use US dollars):

Salaries/fringe benefits: $ 62,400

Equipment: $ 4,000

Supplies: $ 18,400

Travel: $ 7,940

Participant Incentives: $ 0.00

Laboratory testing: $ 0.00

Other: $ 47,260

Total: $ 140,000

Study Title: Observational Study of Treatment Effectiveness and Resistance Patterns among Women

Initiating Treatment with Non-nucleoside Reverse-transcriptase Inhibitor-based (NNRTI) HAART after

Previous Single Dose Nevirapine (SD NVP) in Pregnancy

Time and money summary: The study started in FY05. Participant follow up is expected to be completed by

February 2008; data cleaning and laboratory specimen processing will continue for approximately 2 to 3

months beyond the last participant visit.

Local Co-investigator: Dr Jeffrey Stringer of Centers for Infectious Diseases Research in Zambia (CIDRZ)

and University of Alabama at Birmingham (UAB) is the Principal Investigator and Dr Isaac Zulu of Centers

for Disease Control and Prevention Zambia (CDC) is the local Co Investigator.

Project description : This is an ongoing prospective cohort study of women starting NNRTI-based

antiretroviral therapy (ART) with and without prior exposure to single-dose nevirapine (sdNVP) to prevent

mother-to-child HIV transmission. Some data from other settings suggest that women with prior sdNVP

exposure for PMTCT may not respond as well to NNRTI-containing regimens when seeking treatment for

their own health. Other data suggest this may not be the case, or that it may only be true for women with

very recent sdNVP exposure. This TE seeks follow-on funding for an ongoing CDC-funded, multi-center

study that is being conducted in Zambia, Thailand, and Kenya. The majority of patients are being followed in

Zambia.

Evaluation Question:

The study intends to examine:

•The effectiveness of NVP or other NNRTI-based HAART in HIV-1 infected women who are initiating

treatment after previously being given SD NVP prophylaxis in pregnancy as compared to women who have

not received SD NVP.

•Whether viral resistance patterns in HIV-1 infected women who initiate treatment with NNRTI-based

HAART after previously being given SD NVP prophylaxis in pregnancy as compared to women who have

not received SD NVP.

•The safety and tolerance of NNRTI-based HAART regimens among HIV-1 infected women who initiate

treatment with NNRTI-based HAART after previously being given SD NVP prophylaxis in pregnancy and

among women who have not received SD NVP.

Status of study/progress to date: Enrollment began 21 June, 2005. All international study sites completed

enrollment in January 2007. The Lusaka site enrolled 509 out of 878 total study enrollments. As of end July,

2007, 313 (61%) had completed the study 12 month follow up visit.

Lessons Learned: The Lusaka site has been able to successfully recruit participants for this observational

study. Analyses are not completed as data are still being collected. The Lusaka site has shown that with the

right recruitment strategy it is possible to recruit large numbers of NVP exposed women for research

studies. Close collaboration with the PEPFAR funded ART clinics and the selection of appropriate

participants was the key components to recruitment. In the evolution of the recruitment strategy we found

that it was necessary to approach women about the study when they were seeking HIV/AIDS care for the

first time. Passively relying on referrals did not work. Study staff, working closely with the district ART staff,

identified potential study participants at their first ART screening visit and presented them with study

information. Additionally, working with the community outreach workers these women were prioritized for

follow up if they missed any study or non-study related clinic visits. Just as important as early contact with

the participants is critical selection of participants. With experience the study staff was able to critically

assess the potential participant's level of dedication and interest in the study. Over time this was reflected

in dramatically improved retention rates. Our success has been to work seamlessly within the district

setting.

Information Dissemination Plan: The study results will be widely disseminated abstract presentation at local

and international conferences and publication in peer reviewed journals, as well as to the local community,

including the medical and scientific communities.

Planned FY08 activities: In FY08, support will allow the clinic-based study team to continue following up the

enrolled cohort of women through the 12 month study visit, or primary study endpoint. Continued laboratory

processing will occur during this funding period. Data cleaning and quality control efforts will shift from the

baseline data to the 6 month and 12 month data, tolerability, resistance, adherence, and mortality data. In

2007 the site team shipped one batch of specimens to CDC for resistance testing; in FY08 the second and

final batch of specimens will be sent to the CDC. In FY08, several sub studies will be prepared using the

cleaned data, as well as the main analysis.

Budget Justification for FY08 monies (please use US dollars):

Salaries/fringe benefits: $253,300

Equipment: $0

Supplies: $2,000

Travel: $1,200

Participant Incentives: $0

Laboratory testing: $93400

Other: $0

Total: $ 349,900

Title of Study: Population-level surveillance of antiretroviral drug resistant HIV in Zambia

Time and Money Summary: Started in FY07. $342,586 will be spent from the FY07 grant and $400 000 is

needed for FY 08.

Local Co-investigator: Dr Jeffrey Stringer of Centers for Infectious Diseases Research in Zambia (CIDRZ)

and University of Alabama at Birmingham (UAB) is the Principal Investigator.

Project description:

This evaluation will investigate the prevalence of antiretroviral drug resistance among HIV-infected

populations in Zambia. Two specific groups will be targeted through this surveillance: (1) individuals recently

infected with HIV, and (2) patients currently on antiretroviral therapy (ART). This TE will provide critical

information for national-level decision-making, particularly for optimization of the country's first-line HIV

regimens. It will also provide an epidemiological baseline for further work in this important area.

Evaluation Question:

As access to ART continues to expand rapidly through the region, there are important public health

concerns regarding the development and transmission of resistant HIV strains among the general

population. Many groups, including the World Health Organization, have advocated viral drug resistance

surveillance, especially in settings where the incorporation of resistance testing into clinical care is not

feasible. Through this targeted evaluation, we will support the Zambian Ministry of Health's effort to evaluate

the prevalence of drug-resistant HIV strains at a population level. Results will determine trends in HIV

resistance patterns, which in turn will inform local policy regarding the most appropriate treatment regimens.

Methodology:

1. Surveillance of ARV drug resistance among recently-infected individuals

For the first part of our evaluation, we will target individuals recently diagnosed with HIV through VCT. Two

units will be targeted at each surveillance facility: patients seeking STD treatment services and antenatal

clinics. We believe these groups to be particularly suitable for assessing risk for ARV-resistant HIV

transmission. Both are selected as they may represent different types of high-risk exposure.

Following VCT, left-over blood specimens will be collected from individuals who have tested HIV-positive.

This will be anonymous: no personal identifiers will be attached. Following collection of these left-over

samples, we will perform a two-step screening mechanism. First, all HIV-positive blood specimens will be

tested using the "detuned" enzyme immunoassay. Previous work has validated this technique for the

detection of incident HIV infection in surveillance studies. In this smaller subset of recent infections, we will

perform genotyping for ARV drug resistance. Using this surveillance method, we will be able to determine

HIV incidence at a population level and obtain important information regarding the recent transmission of

drug-resistant HIV strains.

According to our estimates, approximately 10,000 blood specimens will be collected in a two-month period

from all four sites. Assuming a 2% rate of incident HIV infections, 200 samples will undergo genotypic

resistance testing for HIV. With this sample size, we will be able detect an estimate with relative Incident

rates of 2% or 10% will yield 95% confidence intervals of 1.7 - 2.2 % or 9.7 - 10.3% respectively.

2. ARV drug resistance surveillance for individuals on ART

We will also perform drug resistance surveillance on individuals in CIDRZ-supported GRZ ART programs

currently undergoing HIV treatment. This evaluation will assess the prevalence of specific drug mutations in

a population of ART-experienced individuals. Because these results will be useful to guide clinical care, this

survey will not be performed in an anonymous fashion.

In contrast to the above surveillance populations, the design of this portion of the resistance surveillance will

require substantially more input from the various clinical stakeholders throughout the country and from the

Ministry of Health and National AIDS Council. Thus, protocols stating which patients qualify for this activity

(e.g. those suspected to be failing first line therapy or those judged non-adherent) will be worked out at a

later date in broad consultation with local and international experts. We anticipate need to perform

approximately 1,000 samples for this analysis.

Population of Interest:

As described above, 3 populations will be targeted: (1) individuals accessing STI treatment services, (2)

women enrolled in PMTCT programs, and (3) patients currently on ART. We will perform activities across

five Zambian cities: Lusaka (Lusaka province), Ndola (Copperbelt province), Mongu (Western province),

Chipata (Eastern province), and Livingstone (Southern province). We will coordinate with the Tropical

Disease Research Centre and CDC to take advantage of on-going sentinel surveillance.

Status of study / Progress to Date: In FY 2007 the protocol will be developed for ethical review. It is

anticipated that finalization of the protocol will occur in September 2007, when it will be submitted to the

University of Zambia Research Ethics Committee and the University of Alabama at Birmingham Institutional

Review Board. Staff will be identified and hired; procedures for specimen selection will also be developed.

To support this PHE systems will be developed for specimen collection and transport; and laboratory testing

capacity will be established as needed for this surveillance activity. It is planned that full implementation of

the PHE activities will start in February 2008.

Lessons Learned: We have learned useful lessons in study protocol development and budget preparation.

However, a understanding of the prevalence of viral drug resistance within newly tested HIV-infected

individuals will only be understood once surveillance activities commence.

Information Dissemination Plan: The study results will be widely disseminated through in Country

dissemination meetings, abstract presentation at local and international conferences and publication in peer

reviewed journals.

Planned FY08 activities: In FY08, we implement specimen collection procedures and perform viral drug

resistance testing.

Budget Justification for FY08 monies (please use US dollars):

Activity Narrative:

Salaries/fringe benefits: $82,500

Equipment: $0

Supplies: $0

Travel: $0

Participant Incentives: $0

Laboratory testing: $206,250

Other: $111,250

Total: $400,000

Title of Study: Causes of Early Mortality in Adults Starting ART

Time and Money Summary: Study Year 2; Started in FY07 and expected to be completed in FY09; $350

000 is expected from FY07 disbursement and $350 000 is needed for FY08

Local Co-investigator: Dr Jeffrey Stringer of Centers for Infectious Diseases Research in Zambia (CIDRZ)

and University of Alabama at Birmingham (UAB) is the Principal Investigator and Dr Isaac Zulu of Centers

for Disease Control and Prevention Zambia (CDC) is the local Co-Investigator.

Project description: In recent years access to antiretroviral therapy (ART) has expanded globally through

effective international initiatives in partnership with local health authorities. Dramatically favorable clinical

outcomes in many nations including Zambia, have been reported in large numbers of HIV-infected patients

initiating ART. Responses to ART and survival rates after one year in ART programs in developing

countries appear to be comparable to those in developed countries. However, mortality during the early

periods (defined as the first 90 days of initiating ART) has been noted to be significantly higher in

developing compared to the developed world.

At our PEPFAR funded site in Lusaka, Zambia, we have observed that anemia (defined as Hgb <8 mg/dl),

lower BMI (BMI <16 kg/m2), and advanced disease (defined by either WHO stage >III or CD4 count < 50

cells/mm3) are factors associated with increased early mortality. Similar observations have been made in

other cohorts from low-income nations. It is unclear, however, if these factors alone are the most important

and common causes of early mortality of HIV-infected individuals initiating ART in this setting. Elucidating

the common primary causes of early mortality is an essential first step in developing interventional studies.

The specific aims of this PHE are; 1.To characterize the types and nature of opportunistic infections and

other co-morbidities among ART recipients at high risk for early mortality and to determine their incidence

and timing of occurrence in the cohort; 2.To identify the causes of the 90-day mortality observed among HIV

-infected adults initiating ART who are at high risk for early deaths; and 3. To evaluate changes in early

mortality rates through more aggressive medical assessments among those presenting for ART at high risk

for early death using historical rates of early mortality of high-risk patients in Lusaka.

To elucidate the role infections play in early deaths, we will recruit 300 ART-naïve Zambian adults with

HIV/AIDS who are starting ART and are at high risk for early mortality (advanced disease, severe anemia or

low BMI) to the outpatient clinic at University Teaching Hospital (UTH)'s Center for Infectious Diseases. The

study participants will undergo extensive baseline testing, well in excess of what is provided through current

Zambian National Guidelines for HIV/AIDS Care and Support. We will follow them prospectively for 1 year

with scheduled follow-up visits at weeks 2, 4, 8, 12, 24, 36, and 48. However, when the study participants

present with symptoms or signs suggestive of clinical decline, either at scheduled visits or detected during

home visits by study staff, we will perform intensive physical and laboratory diagnostic tests of illnesses by

admitting them to UTH. At UTH, the thorough diagnostic testing will include assessment of routine blood

parameters, microbiological assays, radiological investigations and other more invasive procedures as

indicated based on presentation. Patients will be initiated on medical treatments at UTH guided by the

results of the diagnostic testing and then referred back to the study clinic until completion of first year of

ART or death. For participants who die, we will approach family members to seek permission to perform

autopsies to determine cause of death. When permission for autopsies is not obtained, causes will be

attributed by either medical chart data or verbal autopsies for those occurring outside of heath care facilities.

With this knowledge, clinical algorithms aimed at reducing the disproportionately high early mortality

currently observed in HIV-infected persons on ART in developing countries could be developed.

Status of study/Progress to Date: The study protocol has been submitted to the University of Zambia

Research Ethics Committee and will also soon be submitted to the UAB and CDC Institutional Review

Boards (IRB) and we expect the review process to be completed by October 2007. Recruiting of study staff

and development of recruitment and referral process between UTH and Lusaka Urban Clinics is underway.

We expect to start recruiting study patients by February 2008.

Lessons Learned: We have learned useful lessons in study protocol development, budget preparation and

submitting the protocols to the IRBs. We are also learning useful lessons and developing expertise in

establishing study recruitment and referral systems between UTH and the primary care centers in Lusaka

Urban District.

Information Dissemination Plan: The study results will be widely disseminated through in Country

dissemination meetings, abstract presentation at local and international conferences and publication in peer

reviewed journals.

Planned FY08 activities: In FY08 we plan to accelerate patient recruitment and follow up towards the target

of 300.

Budget Justification for FY08 monies (please use US dollars):

Salaries/fringe benefits: $ 123 089

Equipment: $53 000

Supplies: $ 13114

Travel: $10 714

Participant Incentives: $12 594

Laboratory testing: $113 000

Other: $ 23829

Total: $ 349340

This activity may appear as though it has decreased but this is due to the removal of the public health

evaluations. However, additional plus-up funds have been added to this activity.

Elizabeth Glaser Pediatric AIDS Foundation (EGPAF) and the Center for Infectious Disease Research in

Zambia (CIDRZ) propose expansion of the antiretroviral therapy (ART) service support to the Government

of the Republic of Zambia (GRZ) sites. In FY 2007, there were five components to this activity: (1)

expansion of services to 12 new sites in three new districts; (2) increased focus on pediatric care and

treatment; (3) ongoing focus on quality of care and on continuing quality improvement; (4) a pilot model of

HIV care and treatment for street children and orphans and vulnerable children (OVC) residing in

orphanages based on lessons learned; and (5) the development of a pilot community-based adherence

support program at select sites. There where five public health evaluations (PHE) under this activity in

PY2007.

EGPAF-CIDRZ-supported GRZ sites have enrolled 95,145 adults and children and started 59,084 on ART

as of the end of April 2007. Presently, 45 ART sites in Lusaka, Eastern, Western, and Southern Provinces

are being supported. EGPAF-CIDRZ has trained 1,184 health care workers in adult & pediatric ART

delivery. EGPAF-CIDRZ has presented 23 abstracts, published five papers with seven additional papers

currently in preparation.

Building on past successes, in FY 2008, CIDRZ will continue to support sustainability and scale-up of

services through the following activities: support 12 new sites in the Eastern, Western, Southern, and

Lusaka Provinces selected in consultation with the Provincial Health Offices; enabling an additional 42,000

individuals to start on ART and an additional 81,000 individuals to enroll in the HIV care and treatment

program in all 68 sites over the 18-month period from March 2008 through September 2009. Services in

the rural areas of the four Provinces supported by CIDRZ receive the same level of technical and material

support as the more central district hospitals and clinics. However, CIDRZ is training and empowering the

District offices to provide appropriate clinical oversight and quality assurance to those clinics.

EGPAF-CIDRZ has not yet met the target of at least 15% of ART clients being children due to the continued

difficulty in recruiting pediatric patients. EGPAF-CIDRZ's approach to improving pre-existing pediatric care

will include: ongoing clinical mentoring, training of all providers in EGPAF-CIDRZ supported sites (pediatric

training is one week and participants receive a certificate only after having achieved an 85% pass rate)

complimentary aspects of pediatric care, training of at least two pediatric peer educators at each site, and

introducing and strengthening basic child health interventions into the ART program. CIDRZ will liaise with

JHPIEGO to ensure double reporting on pediatric training does not occur.

The project aims to increase the number of children accessing care and treatment by: introducing routine

testing into all in-patient facilities, the development of more formal linkages for strengthening the routine

identification of HIV exposure status of infants at maternal and child health (MCH) facilities, training 200

health care workers in pediatric ART management, targeting community growth and development programs

to improve early recognition of clinically HIV- infected infants, by strengthening infant diagnoses with

training in polymerase chain reaction (PCR), and utilizing pregnant women, PMTCT and TB programs, and

siblings as index cases to access other children for VCT.

As part of the strengthening of pediatric services, EGPAF-CIDRZ will step-up its focus on community

mobilization and education. In FY 2008, there will be a pilot project to train trainers in outreach through

puppet shows, including the development of pediatric appropriate scripts, music, and messages.

During FY 2008, the quality of care activity will train an additional six trainers in the provinces. These

trainers will train a further 30 nurses. The provincial model will be adapted to use a distance learning-

modular framework, whereby participants will complete coursework and assignments by distance,

electronic, or web based before completing the mentoring component with their trainer/mentor. These

nurses will be continuously evaluated through regular, formal on-going assessments each quarter, chart

audit and through comparing quality of care in clinics where the training has not occurred to clinics where

training has occurred. Triage training comprises a week of didactic training and 100 hours of clinical

mentoring. Participants receive a certificate if they achieve greater then 85% at the post-test and if they

pass their competency test at the end of the training.

Using Plus-Up funds ($1M total for scaling up infant HIV diagnosis nationwide in Zambia), EGPAF-CIDRZ

will collaborate with the Lusaka, Eastern and Western Provincial Health Offices and the National Infant

Diagnosis Reference Lab at the University Teaching Hospital to make infant HIV diagnosis using dried

blood spots available throughout rural and urban areas of the three provinces. The activity will link in

closely with PMTCT services and infant follow-up at all health centers supported by EGPAF-CIDRZ within

the provinces. Earlier HIV diagnosis will lead to earlier referral and start of ART at a much younger age,

leading to improved long-term outcomes.

In addition to the above, the next version of SmartCare will enable CIDRZ staff to pull data related to the

review of symptoms, physical examination findings, investigations, and treatment provided. All sites are

provided with a computer and data associate who record all patient data into SmartCare. Quality assurance

is undertaken by analyzing the input and providing feedback and recommendations to the sites. Monitoring

visits are also done on a quarterly basis to assess clinical care and provide mentoring for clinicians.

Monitoring results are shared with and between clinics so that they are aware of their performance relative

to peer clinics and stimulate improvement. In addition to regular QC reports it is planned to run regular

reports on the percentage of patients who present with symptoms of TB and are investigated for TB and the

percentage of patients who present with symptoms of sexually transmitted infection and are treated for

such.

The CIDRZ supported Central Lab (Kalingalinga) and provincial labs located in district hospitals are well

equipped to provide services in for patient diagnosis, treatment and monitoring. Baseline and follow-up

hematology, chemistry, CD4 and viral load testing (where available) for all CIDRZ supported sites are

performed in accordance with Zambian Ministry of Health guidelines. In Lusaka all lab investigations are

centralized at the CIDRZ Central Lab which allows efficiency in reagent ordering, equipment maintenance

and quality control. In the provinces and rural areas lab services are decentralized in district hospitals. In

this setting consistent access to laboratory testing for patients on ART has been challenging due to weak

Activity Narrative: reagent supply chain, poorly trained technicians and poor instrument maintenance. CIDRZ continues to

work with CDC and MoH to improve provincial lab capacity by installing new equipment and training staff in

good lab practice. CIDRZ is also strengthening MoH reagent supply chain forecasting, ordering and

delivery. CIDRZ continues to supply back-up reagents and supplies. New CIDRZ teams, located in the

provinces, will intensify oversight and will include a dedicated lab technician to provide closer on-site

supervision.

If the transition to first line use of Tenofovir-based regimen the Central Lab is in a good position to provide

the needed support. Baseline creatinine is presently done for all patients enrolled in HIV care and

treatment. Creatinine is also done on follow-up visits for patients with abnormal baseline values. For

patients on Tenofovir clinical staff has been trained to monitor creatinine at baseline, three and six months.

Clinical staff has also been trained to calculate creatinine clearance and dose adjust medications (including

ART) as necessary. As described above lab capacity to perform creatinine monitoring is already available

and in place in Lusaka and improving access in the provinces is well under way.

Despite intensive efforts, the ART Program at Kamwala, focusing on street children and orphans living in an

institutional setting, has not been very active. Although we have finally received official permission to test

these minors in the absence of a legal guardian, we have encountered additional problems and are

therefore not in a position to scale up this model. We will, however, continue to work with Fountain of Hope

to establish ART services as originally planned.

We will work closely with the DHMT's to develop an effective model in which community and support group

members can assist health care workers within the clinic setting. CIDRZ will provide further training to

community members in the areas that can assist in decreasing the burden of patient care on existing clinical

staff and help formally integrate these community members and activities into the ART clinics.

Traditionally HIV prevention efforts have focused on HIV-negative individuals. "Positive Prevention" aims to

protect the health of HIV-infected individuals and prevent the spread of HIV to sex partners. The rapid scale

-up of care and treatment has created an important opportunity to reach many HIV-infected individuals and

clinic-based prevention interventions aimed at people infected with HIV will be included together with

counseling on ARV adherence and alcohol use.

The following activity is newly proposed for FY 2008 with Plus-up funds.

This activity is linked to UTH Virology, CDL, SCMS, Eastern, Western, Southern and Lusaka Provincial

Health Office laboratory programs, as well as to the CIDRZ Central Laboratory at Kalingalinga Clinic.

The Elizabeth Glaser Pediatric AIDS Foundation (EGPAF)/CIDRZ ART and prevention of mother to child

transmission of HIV (PMTCT) activities are supported by a Central Laboratory at Kalingalinga District Clinic.

This centrally-located facility set up in Lusaka District, known as the CIDRZ Central Laboratory (CCL),

performs multiple assays designed to provide clinical support for the service programs and the ongoing

projects at CIDRZ. The laboratory performs assays on clinical specimens for hematology, clinical

chemistry, clinical microbiology, coagulation, HIV diagnostics, molecular biology diagnostic, serology,

specimen archiving, and HIV monitoring (CD4 counting and HIV viral load). Clinical specimens are

transported to the laboratory from various clinics and hospitals throughout Lusaka and Zambia. Specimen

processing and testing is performed by trained and certified laboratory staff using state-of the-art

instruments and necessary support equipment. All specimen records are managed with a computerized

laboratory information system, which is interfaced with the high-throughput instruments in the laboratory.

Complete client test results reports are generated for each specimen received and distributed to the

appropriate clinic.

Currently, CCL is performing approximately 9,000 CD4 tests, 9,600 complete blood counts (CBC's), 5,100

chemistry (liver and kidney function tests), and 2,100 syphilis tests per month for the EGPAF/CIDRZ ART

and PMTCT programs. The number of molecular biology tests performed is increasing to approximately

560 HIV RNA viral loads and 360 HIV DNA polymerase chain reaction infant diagnostic tests. The

laboratory is currently setting-up tuberculosis (TB) testing and estimate performance of 5,000 tuberculosis

(TB) cultures per year on HIV positive TB smear negative patients with symptoms and those appearing to

fail in early TB therapeutic phases.

The CCL was built in 2001, and expanded in 2004 to accommodate its increased responsibilities. The

building is approximately 5,000 square feet and includes seven laboratory rooms (main laboratory,

specimen processing, microbiology, PCR analysis, PCR clean, autoclave, freezer/repository) and ten

support rooms (reception, utility, staff, computer/server, conference, three offices, bulk storage, and kitchen.

The large main laboratory area is set-up for automated and manual testing of blood samples including CBC,

CD4 counting, chemical analysis and serological rapid testing including HIV and Rapid Plasma Reagin

(RPR) syphilis testing. A level II bio-containment suite is used for microbiological testing with two class II

bio-safety cabinets. TB culture testing will be performed in this suite using the Becton Dickinson Company

Mycobacteria Growth Indicator Tube (MGIT) liquid culture system. Two additional suites are available for

PCR amplification preparations.

The CCL performs multiple assays to support project HEART. The most common assays performed on

primary instruments with back-up plans to include the following for various analyses: Hematology-Complete

Blood Count, 5 part differential is performed on Sysmex XT 2000i and XT 1800i Hematology Analyzers on

site. A Sysmex Pochi at Kara Clinic in Lusaka is a contingency if both of the onsite analyzers are down.

Chemistry analytes for liver and kidney function are performed on two Roche COBAS Integra 400+

analyzers; these analyzers serve as backup for each other. CD4+/ CD 8+ lymphocyte counting is

performed on three Beckman Coulter Epic systems and a back up system is located at Kara Clinic in

Lusaka.

Coagulation testing profiles include prothrombin time, partial prothromboplastin time and activated partial

thromboplastin time. These are performed on a Sysmex 560 coagulation analyzer. For back up, the

samples are frozen until they can be performed.

Sexually transmitted disease testing for Neisseria gonorrhoeae and Chlamydia trachomatis are performed

on the Becton Dickinson Probe Tech system. Other molecular biology testing using Strand displacement

and nucleic acid amplification for TB identification are also performed on the same system. As a

contingency plan samples are processed and frozen until they can be analyzed.

Quantitative viral load testing is performed primarily on the Roche Cobas system if this system fails manual

kit preparation for detection is performed. Systems for infant HIV infant PCR amplification include the

Stratagene Mx3000 Light-cycler, Applied Bio-systems Gene Amp 2700 thermo-cycler and BioTeck ELX

ELISA equipment. If these systems fail, samples are tested at the University Teaching Hospital Pediatric

laboratory or samples are processed and stored until they can be tested.

Rapid TB culture is performed on the Becton Dickinson MGIT liquid culture system. In the case of failure,

the cultures will be performed at the National Chest Diseases Laboratory on the same system in Lusaka

through a memorandum of agreement.

Herpes simplex virus, syphilis and hepatitis serology testing is performed using BioTeck ELX ELISA or

Roche Elecsys 2010 equipment.

Provincial Laboratory Plans:

As Project Heart continues to scale-up in Western, Eastern, and Southern Provinces, one challenge to

effective care and treatment is the lack of qualified laboratory staff and appropriate laboratory equipment.

Most provincial clinics outside of Mongu district center have little laboratory equipment other than a

microscope. To provide the highest quality standard of care in these settings, EGPAF/CIDRZ is

collaborating with the provincial and district lab managers to initiate a sustainable specimen

transport/logistics system from those sites that are within 50km of the district and provincial hospitals. For

those sites outside of this radius, we will assist a larger rural site with CD4, chemistry, and hematology

instruments if there are qualified staffs available and where other rural sites will most effectively be in a

position to transport specimens to the site with the capacity to provide the tests. These would be sites that

are too far from the district and provincial hospitals. In FY 2006, five Guava CD4 instruments (Guava

Technologies, Hayward, CA) where placed in strategic centers within 3 Provinces: Chikankata, Choma, and

Livingstone (Southern), Senanga (Western Province), and Petauke (Eastern). CD4, chemistry, and

Activity Narrative: hemoglobin instruments with appropriate training to seven of the 14 new provincial sites will be provided.

The placement of these instruments will also allow for further scale up to more rural sites within the 50km

radius of these seven strategic sites that have the capacity to manage tests. This support is provided to

these provinces and linked to support provided by CDC cooperative agreements.

Laboratory staff requires further training in use and maintenance of existing and new instruments. Two

trainings for 25 staff each in FY 2008 focusing on the use, repair and maintenance of both the existing and

newly acquired instruments to ensure sustainability of laboratory capacity. The lab will also expand and

increase its capacity to conduct resistance testing.

The funding level for this activity in FY 2008 has increased since FY 2007.

The increase amount, $5,240,000, will be dedicated for national scale-up commodity purchases through

EGPAF, in accord with guidance regarding ceilings and exception allowed for commodity purchases.

Narrative changes include updates on progress made and expansion of activities.

This activity relates to: JHPIEGO SI (9034), AIDSRelief-Catholic Relief Services (CRS) (#8828), Ministry of

Health (MOH) (#9008), Technical Assistance - Centers for Disease Control and Prevention (CDC) (#9023),

and COMFORCE (#9691).

The Continuity of Care Program tools consist of health data and services standards, equipment (a touch

screen monitor, clinical computer, un-interruptible power supply, smart card reader and cards), health care

protocols embodied in clinical forms, systems documentation, and software. These tools are being refined

and scaled-up, and taken together with large numbers of trained users, to provide a national Electronic

Health Record (EHR) system to better assure high quality HIV/AIDS care. The software is now called the

SmartCare System and represents a consolidation and standardization of multiple systems operations.

This clinical application is designed to provide a complete view of a patient's health, at every point of care

that may be accessed by an HIV positive person. The program targets the linking and integration of all

potentially HIV/AIDS related out-patient services via an informational medium (a smart card) that is portable

across service providers and points of care. This is intended and expected to improve the quality of care

and reduce the cost of services through a number of synergistic effects revolving around complete

longitudinal clinical information access and use through reports such as late patient report, treatment failure

report, PEPFAR reports, HMIS reports, and WHO's Early Warning Indicator report and many others.

Whereas in FY 2005 and early FY 2006 the SmartCare software development effort reflected primarily an

effort to merge (into the Continuity of Care framework) the two earlier efforts (the Centers for Disease

Control and Prevention (CDC) Continuity of Care EHR Program and the Center for Infectious Disease

Research in Zambia (CIDRZ) Patient Tracking System (PTS) software), the activity of 2007 was focused on

increasing the system functionality and preparation for national scale-up training and implementation, which

began in June with the training of more than 150 District Health Information Officers , MCH Coordinators,

District Directors of Health and Management and Planning Directors. This was followed by more in-depth

District-focused trainings of Lusaka and Central Provinces in August 2007, Southern Province in

September, two more in October, and the remainder by mid December. Over 60 sites have deployed

SmartCare and about 100,000 patients are enrolled.

Increasingly the Zambia Ministry of Health (MOH) is taking leadership in engaging collaborators, providing

authority for deployment, and contributing field support from within the Ministry. In mid FY 2006, the MOH

corralled the efforts of all major care and treatment implementers, asking each for commitments of

infrastructure for deployment of the system nationwide. Recently, the MOH formally requested support from

USG for deploying to 900 locations in the next 18 months.

On April 5, 2006, the MOH established this system as the Zambian national standard for electronic clinical

systems, thus displaying a remarkable achievement of national leadership and consensus as well as

technology assimilation in a short period of time. The immediate targets of this effort remain constant: the

quality of health care in Zambia and ‘local ownership' by the MOH. However, when the software is

internationalized, which is an extension of functionality now underway, we expect it may fill a niche in some

other PEPFAR countries, thus, leveraging the investment made in Zambia. The application is open source

and we hope other countries will continue to express interest in piloting the application as it matures in

Zambia.

The services which have been integrated to date are HIV care, antiretroviral therapy (ART), tuberculosis

(TB) care in the context of ART, antenatal clinic services (ANC), prevention of mother to child transmission

(PMTCT) protocols with opt-out counseling and testing (CT), labor and delivery, and voluntary counseling

and testing (VCT). Pediatric ART services have been presented and are ready to pilot. This developing

country EHR provides now services more than 80,000 patients, and with the additional partners starting

deployment during 2007, the rate of growth of services may increase non-linearly as the number of

electronic clinics increase, provided there are no drug supply limitations.

The EGPAF activity in FY 2007 included: 1) support for some of the equipment required for the national

scale-up; 2) contributing software development resources via subcontractors and the hiring of national staff

to the collaborative software development guided by CDC and the MOH; and 3) ongoing training of the core

capacity to support this technology in country, including some supportive and collaborative work with

Microsoft volunteer trainers, who contributed about 6 person weeks in FY 2007

In FY 2008, EGPAF will 1) substantially increase computer and smartcard support (via large commodities

purchase to supply essentially medical record equipment to one third to one half of the 1584 clinics and

portable medical records to 1.7 million; the amount for this commodities purchase represents the totality of

the EGPAF budget increase for FY2008), 2) continue to provide software resources through contractors but

will further transition support for Zambia specific components to contractors with a strong in-country

presence, and increasingly to locally employed staff, and 3) significantly expand support for training through

5 Peace Corps extension volunteers and/or Crisis Corp volunteers to assist with national scale-up.

Mentoring of the ministry software developers will also be expected of the soft-ware contractors, and this

will be done in part in collaboration with expected increases in Microsoft volunteer trainer contributions in FY

2008. Additionally, EGPAF will provide logistics support for the MOH scale-up including, maintaining the

SmartCare workspace and warehouse, and employing an administrative manager to support the project

director.

Zambia's Health Management Information System (HMIS), a specific key MOH facility-based aggregate

data collection tool, will experience improved data timeliness, quality, completeness as a consequence of

SmartCare replacing significant parts of the manual tally system, in the clinics that are prepared to ‘go

electric'. All facility based HMIS indicators can be produced as a side-effect report of routine recording of

patient care data. This information will feed directly into the HMIS software before the end of 2007,

conditioned on the new HMIS specifications being finalized by the MOH, thus improving the sustainability of

the HMIS system and minimizing duplication.

Activity Narrative:

The mapping capacity provided by end of FY 2007 will become full GIS functionality in 2008, and will

support mapping of PEPFAR static data in addition to dynamic patient and provider data at all facilities,

districts and MOH administrative levels. Specific efforts are being initiated via other partners to encourage

automation of linkage of NAC National AIDS Reporting Form data with facility data at district level to further

enrich information available for local decision-making.

In FY2008, particular emphasis will be given to support for outpatient malaria, TB and STI services, in light

of substantial interactions of these diseases with HIV care and prevention. The Care Card smart card will

provide the referral continuity between services such as CT, TB, PMTCT and ART.

During the last half of 2006 and early 2007, updated national HIV/AIDS care standards were incorporated

reflecting the latest guidance of the MOH and the growing experiences of a broad user community. These

standards are reflected in the new SmartCare forms that all ART providers in Zambia must now use. In FY

2008, the following ongoing interdependent activities will be supported: (1) completing the full outpatient and

pediatric service functionality of SmartCare to more effectively and to fully support care and treatment for

people who may have HIV/AIDS and related illnesses; (2) adapting a version to support repeat blood

donors as part of a blood supply safety initiative; (3) working with orphans and vulnerable children (OVC)

service providers to identify the optimal intersection between ‘well-care' services in this context and health

care; (4) improving the human capacity of the MOH both centrally and in clinics to operationally own and

manage this national EHR application; and (5) supporting continued deployment of the SmartCare

application nationwide at MOH sites, and in those MOH sites supported by different United States

Government- and privately - funded partners, now including CIDRZ, Catholic Relief Services, ZPCT ,

Churches Health Association of Zambia, CHAMP, LinkNet, Konkola Copper Mines, Flying Doctors, and

others in collaboration with DOD, State, Peace Corps, and USAID, all of whom are now actively engaged

with SmartCare national deployment. SmartCare will be central to generating data mentioned in the MOH,

NAC, and other SI and Systems Strengthening mechanisms.

Targets set for this activity cover a period ending September 30, 2009.