The PHE "How to Optimize PMTCT Effectiveness (HOPE) Project" has been approved for inclusion in the

FY 2009 COP. Its tracking number is TZ.08.0203.

New/Continuing Activity: New Activity

Continuing Activity:

Emphasis Areas

Human Capacity Development

Public Health Evaluation

Estimated amount of funding that is planned for Public Health Evaluation

Food and Nutrition: Policy, Tools, and Service Delivery

Food and Nutrition: Commodities

Economic Strengthening

Education

Water

Table 3.3.01:

This PHE activity was approved for inclusion in the COP. The PHE tracking ID associated with this activity

is TZ.08.0147.

THIS IS AN ONGOING PHE ACTIVITY. THE ACTIVITY HAS NOT CHANGED FROM FY 2008.

Title of Study:

New multi-country study: Enabling People Living with HIV/AIDS (PHA) to serve as change agents for HIV

prevention and treatment adherence.

Expected Timeframe of Study:

2 years. The protocol will be developed, the intervention will be implemented, and data will be collected

during the first eighteen months of the project. Following that, there will be analysis and report and

manuscript preparation

Local Co-investigator:

This is a multi-country evaluation coordinated by Dr. Alex Coutinho, Director Designate of the Infectious

Diseases Institute in Kampala, Uganda and will be carried out with PEPFAR support in Uganda, South

Africa, and Tanzania. The local partner(s) remain to be determined but will be selected from among the

current PEPFAR-Tanzania treatment partners.

Project Description:

The goal of this PHE is to develop a model for enabling PHA to serve as change agents for prevention,

adherence, disclosure and stigma reduction within their social networks and communities; and to test the

effectiveness of this approach. The process will include creating/sustaining a stigma-free clinic environment

as a secure platform for clinic-based outreach; training PHA to be change agents using Appreciative Inquiry

adapting established behavioral interventions; assessing resulting behavior change among change agents

and their social networks; and determining the cost of rolling out this model.

Evaluation Question: Hypothesis:

Empowering people living with HIV/AIDS using appreciative training techniques will enable them to

influence behavior, attitudes and well being—within their own social networks. If effective, this will be a

sustainable approach to community management of prevention and HIV as a chronic disease.

Methods:

Clients attending the participating HIV treatment clinics will be randomly selected (by age groups and sex)

and enrolled in four cohorts. Selected clients will undergo training program that uses the Appreciative

Inquiry Technique and is based on the curriculum: "Stepping Stones and Understanding and Challenging

HIV Stigma: A Toolkit for Action". The intervention will be implemented using a step-wedge design so that

individuals act as their own controls until they receive the intervention. Study subjects will undergo interview

assessments every three months over an 18-month period with assessments up to nine months pre- and six

months post-receipt of intervention to assess the change in their behaviors. The structured survey will

address knowledge and self perceptions of stigma, HIV risk, sexual behavior, and adherence. Participants

will also be asked about encounters in which they spoke to members of their network about their HIV status.

Quantitative measures of changes in adherence and risk behavior will be through pill counts, viral loads and

condom usage. Disclosure and advocacy will be measured by the quantity and quality of the interactions

reported. Other measures will include changes in health characteristics (CD4 count, viral load, ART status,

length of time on treatment). Finally, a self-administered mental health screening tool (SRQ20) will be used

to evaluate changes in participants' coping strategies, as a result of the intervention.

Knowledge and behavior in the subjects' networks will be assessed through social network analysis. This is

a method that enables measurement of change in the quality and quantity of communication between the

focal individual and his/her social network. Study subjects will be asked to provide the names of up to 30

people in a social network spanning sex partners, family, friends, work associates, lenders, and community

organizations (such as churches and schools). Every six months, these people will be interviewed to

determine whether the study subject has spoken with each of their network members about the following:

(a) preventing HIV/AIDS (e.g., abstinence, faithfulness, or condoms); (b) testing for HIV; (c) disclosing HIV

status to friends, family member or sexual partners; or (d) seeking appropriate care and adhering to

treatment. We will then ask whether any behavioral action resulted from those discussions (e.g., has the

social network member been tested?).

Technical Assistance

This project has been developed in collaboration with a number of collaborators who will provide necessary

technical support. International collaborators include individuals with skills in network analysis (Rand

Corporation, US); health economics (Rand Corporation, US); Appreciative Inquiry (Kensington Consultation

Centre, UK); and GIS/community mapping (Participatory Inquiry into Religious Health Assets, Networks and

Agencies; and the African Religious Health Assets Programme). In addition, Professor Keith McAdam, who

has developed this project during his tenure as Director of the Infectious Diseases Institute, will provide on-

going support for evaluation design and implementation.

Population of Interest:

The study participants are HIV-infected persons receiving antiretroviral therapy at participating HIV

treatment sites. The sample size is 480 persons and is selected to assess differences in proportion of

network contacts disclosed to; proportion who used a condom at last sex; and proportion of contacts going

for VCT.

Information Dissemination Plan:

There will be regular conference call and e-mail interactions between partners in the project in order to

discuss design process and preliminary observations. Two times each year there will be physical

exchanges between the three country programs, and as part of these exchanges there will be two

stakeholder meetings each year that will rotate between sites. Dissemination priorities will include

Activity Narrative: publishing peer-reviewed articles on findings in key policy journals; and engaging Ministries of Health and

PEPFAR in incorporating findings into their country policies and activities. Local investigators in each

country will be encouraged to take the lead in this process.

Budget Justification: Salary/fringe benefits: $190,000

Equipment: nil

Supplies: $10,000

Travel and consultant fees: $60,000

Participant Incentives: $35,000

Laboratory testing: $25,000

Training (120 x 12 weeks x 4 cohorts): $80,000

TOTAL: $400,000

New/Continuing Activity: Continuing Activity

Continuing Activity: 16535

Continued Associated Activity Information

Activity Activity ID USG Agency Prime Partner Mechanism Mechanism ID Mechanism Planned Funds

System ID System ID

16535 16535.08 HHS/Health Harvard University 6520 3621.08 $400,000

Resources School of Public

Services Health

Administration

Emphasis Areas

Human Capacity Development

Public Health Evaluation

Estimated amount of funding that is planned for Public Health Evaluation

Food and Nutrition: Policy, Tools, and Service Delivery

Food and Nutrition: Commodities

Economic Strengthening

Education

Water

Table 3.3.09:

THIS IS AN ONGOING PHE ACTIVITY. THE ACTIVITY IS UNCHANGED FROM FY 2008.

Title of Study: Impact of primary drug resistance on virological failure of first-line regimen in Tanzania

Expected Timeframe of Study: Two years

Local Co-investigator:

Dr. Said Aboud; Dr. Chalamilla Guerino; Prof. Ferdinand Mugusi; Dr. Claudia Hawkins; Dr. Shabbir Ismail;

Dr. Wafaie Fawzi; Dr. Cecile Tremblay.

Project Description:

Prevalence of baseline antiretroviral drug resistance ranges from five percent to twenty percent depending

on the length of antiretroviral use in a given population, and treatment practices. Baseline drug resistance

could affect response to first-line regimen. Furthermore, non-B subtype, prevalent in Tanzania, may

develop different mutation patterns under the selective pressure of ARVs. We propose to evaluate the

prevalence of baseline drug resistance in our cohort of HIV-infected treatment-naïve individuals to better

inform first-line regimens and to follow annual trends of baseline drug resistance. Further, to characterize

mutation patterns evolving in our patient population, to optimise second-line regimen selection.

Evaluation Question:

1. To evaluate the prevalence of baseline drug resistance in our treatment-naïve patient population:

a. to study the prevalence of drug resistance mutations according to ARV classes

b. to evaluate whether specific mutations, such as the K65R mutation, are common in our treatment-naïve

population and could jeopardize the effectiveness of our first-line regimens

2. To characterize the resistance mutations associated with treatment failure

a. to evaluate the pattern of drug resistance mutations associated with treatment regimen

b. to evaluate whether our second-line regimen is likely to succeed in the context of these mutation patterns

Methods:

Our methodology is based on the standardized CDC/WHO protocol entitled ‘The population based

monitoring of HIV Drug resistance emerging during treatment and related program factors in sentinel ART

sites in resource limited settings' to facilitate cross-site comparisons of baseline resistance data..

Our patient population will be selected from HIV+ subjects enrolled in the MDH program in Dar es Salaam.

Pre-treatment samples on 100 randomly selected patients will be collected to evaluate baseline resistance.

Follow up resistance testing will be performed on these individuals at 12 months or when treatment failure

occurs, whichever comes first. Resistance testing on 100 samples on patients with virological failure to first

line ART will also be performed. Resistance testing will then be performed on baseline samples of the

patients that have mutations present at the time of failure. All of the samples will be identified so that results

can be given back to the patients and to inform decision making. Time of entry into the cohort will be taken

into account in identifying the sampling frame as rates of resistance may change over time in a population.

Plasma HIV RNA will be extracted from samples obtained from treatment-naïve individuals. Sequencing

will be performed using a standard protocol with an ABI sequencer in Botswana Harvard Partnership in

Gabarone. Sequences will be analyzed using Sequencer 4.5 (Gene Codes Corporation software, Ann

Arbor, MI). As a part of internal Quality Assurance/Quality Control, the Botswana laboratory uses routine

phylogenetic analysis and compares sequencing results on plasma RNA and proviral DNA generated in

Botswana and in Boston. Analysis of drug resistance mutations and subtype analysis will be performed

using the Stanford University HIV Resistance Database. Results will then be confirmed using the Los

Alamos HIV blast tool (LANL). An analysis of resistance patterns will be performed by subtype if the

frequency of resistance if sufficient. The comparison will be analyzed using a non-parametric statistical

analysis (Mann-Whitney test using Statistical Packages for Social Scientists 12.0 for Windows). Clinical

data will be collected on each patient at baseline and follow up for inclusion in the analysis. Baseline data

will include: the date of ART initiation, ART regimen, sex, DOB, age, prior ART exposure, CD4 count and

date, WHO stage, viral load and date. Follow up data will include: modifications to therapy during follow up,

level of adherence, CD4 counts and dates, viral loads and dates, endpoint status (death, loss to follow up

etc.) and date.

Population of Interest: To assess the prevalence of baseline drug resistance, 100 plasma samples will be

selected randomly from patients attending the first visit within the same quarter of a calendar year. Follow

up samples on these patients will also be collected as stated in the methods above.

To evaluate resistance mutations patterns associated treatment failure, we will collect 100 plasma samples

at treatment failure (defined as detectable viral load after six months of therapy). They will be sequenced

and analyzed for resistance mutations. Baseline pre-therapy samples will also be sequenced among those

patients who have resistance mutations at treatment failure to evaluate whether baseline resistance was

present. About 15,000 individuals are presently on antiretroviral therapy. With an expected failure rate of

10 to 20% after 24 weeks of treatment, the proposed 100 samples could be collected within the first year of

the study.

Information Dissemination Plan:

We plan to involve local stakeholders including National AIDS Control Programme, Ministry of Health and

Social Welfare and implementing partners early in the development of the research protocol. Results of the

study will be disseminated to these local stakeholders. Results will also be presented at scientific meetings

such as the Conference on Retroviruses and Opportunistic Infections or the Resistance Workshop and

manuscripts will be submitted to scientific journals.

Budget Justification: Salary/fringe benefits: $21,000 (Graduate Student to perform genotypic and

Activity Narrative: phylogenetic analysis of the results)

Equipment: nil

Supplies: nil

Travel: $1500 (one presentation of results at an international meeting)

Participant Incentives: nil

Laboratory testing: (400 samples at $150/samples) $60,000

Other e.g. transport of samples: $2,500

Total: $85,000

New/Continuing Activity: Continuing Activity

Continuing Activity: 16482

Continued Associated Activity Information

Activity Activity ID USG Agency Prime Partner Mechanism Mechanism ID Mechanism Planned Funds

System ID System ID

16482 16482.08 HHS/Health Harvard University 6520 3621.08 $85,000

Resources School of Public

Services Health

Administration

Program Budget Code: 10 - PDCS Care: Pediatric Care and Support

Total Planned Funding for Program Budget Code: $2,134,121

Total Planned Funding for Program Budget Code: $0

Program Area Narrative:

PEDIATRIC CARE AND SUPPORT

There are approximately 140,000 children living with HIV in Tanzania. By the end of 2007 only 11,176 had ever received ART.

Because there is only limited surveillance data specific to children available in Tanzania, estimates of burden have been based on

modeling, and targets have been developed in relation to the number of adults receiving services. The Government of Tanzania

(GoT) is committed to pediatric HIV care and treatment and mandates that 25% of all patients on ARV should be children.

Tanzania's five year strategy for implementation of care and treatment services for HIV-infected and exposed children focused

primarily on procurement of appropriate formulations (both through PEPFAR support and GoT with partners), development of

pediatric care and treatment guidelines, and development of key capacities such as diagnosis of HIV in children including early

infant diagnosis through PCR testing and identification of HIV-exposed children at various entry points. General services (IMCI,

EPI) for children in Tanzania are well run, though there has been limited progress in implementing services for HIV-exposed and

infected children. Guidelines for care and treatment of children with HIV have been developed, and pediatric formulations of key

drugs (ARVs, cotrimoxazole) are available. Several partners support high quality pediatric care and treatment initiatives on limited

scales; for example, a warm consultation line and a Child-Centered Family Care Clinic (CCFCC) has been developed at the

Kilimanjaro Christian Medical Center in Moshi. Despite this progress, there have been some important barriers to scale up of

pediatric services (such as absence of policies related to testing children for HIV including age-specific counseling). Only a small

proportion of those reached during early scale up of HIV care and treatment services were children, most of whom were older

children (between 5 and 15). According to the PEPFAR Annual Progress Report in 2007, children represented 9.2% of those on

ARV treatment and approximately the same proportion in care.

Achievements during the past few years should set the framework to allow for the capacity to provide HIV services for children.

One key step has been the development of a national Pediatric HIV Technical Working Group at the Tanzania National AIDS

Control Programme (NACP). This group is comprised of pediatricians and other technical members from treatment partners,

NACP, UN organizations, and the Tanzanian Pediatric Association. The objective of this group is to move the pediatric agenda

forward, mainly on infant identification, testing, and Provider-initiated Testing and Counseling (PITC), as well as age-specific care

and support for HIV-infected children. In addition, in March 2008, the first national pediatric HIV conference included key

stakeholders such as the NACP, the USG, and the Tanzania Pediatric Medical Association. It was the occasion for the launch of

the national HIV Early Infant Diagnosis guidelines. Another important step is the home testing of families of index HIV patients,

recently initiated in two regions. This effort is resulting in additional children being tested and referred for treatment.

One critical barrier to scale up has been the absence of guidelines for testing infants and children, which has been addressed to

some degree. In April 2008, Tanzania released guidelines for HIV testing and counseling in clinical settings. These guidelines

promote HIV testing as part of the standard of care for all persons attending health care facilities and support the testing of

children when the health care worker (HCW) has determined that testing is in the best interest of the child. The guidelines require

verbal consent for testing of children from parents or recognized legal guardians. These guidelines open the door for expansion

of testing of children in clinical settings. However, there is an urgent need to address remaining policy issues (i.e., testing children

with no designated guardian present), develop practices and guidelines for disclosure to children, and develop training materials,

job aids, and approaches to implementation.

USG staff, in collaboration with Columbia University and other partners, have also worked to address key limitations related to

early diagnosis for infants (EID). EID capacity has been established at the level of the four Zonal referral hospitals. These

laboratories participate in the external quality assurance program supported by CDC Atlanta, and have performed well.

Guidelines for EID have been launched as above, materials have been developed for training of HCWs in collection of dried blood

spot samples, HCWs have been trained, and systems for sample transport have been established. Lab technicians have also

been trained at Bugando Medical Center for each of the zonal laboratories. However, the equipment is currently being installed at

the other zonal laboratories. The guidelines suggest that a PCR testing should be done for all HIV-exposed infants at 4-6 weeks,

or first maternal-child health (MCH) visit.

A review of the initial phase of early infant diagnosis is planned for early 2009 and the findings will inform the way forward.

The package of services recommended for children includes clinical assessment, baseline CD4 and viral load testing (where

available), cotrimoxazole for exposed infants, all HIV infected infants < 1, and all children with stage II, III, or IV disease, and

growth and development monitoring. The national guidelines recommend identification of a designated care provider, and

provision of services to the families of infected children and ART. The recommended first-line regimens are AZT/3tc/NVP for

young children and AZT/3tc/EFV for children over three. Children with documented HIV and clinical disease or immunologic

damage are prioritized for treatment. ART is recommended for children with known HIV exposure and advanced clinical disease,

even if it has not been possible to confirm HIV infection.

Tools to assist with pediatric services (for example, a dosing wheel developed by the Clinton Foundation and a dosing chart

developed by Baylor University and other partners) have been distributed and are available in the field. Based on site visits to

partners, providers report providing cotrimoxazole to HIV-exposed and infected children, but actual rates of uptake are unknown

because documentation requires strengthening and no formal assessment has been done.

With FY 2008 funding from the USG, University Research Council provided technical assistance to support development of

guidelines for infant feeding. Additional FY 2008 funds will support the development of a pilot food supplementation program that

will be operated on the MCH platform. During FY 2009, Baylor College of Medicine will initiate the development of specialist

pediatric HIV treatment centers in the Southern Highlands (Mbeya) and (Mwanza) through a public-private partnership. Part of

their mandate will be to enhance the provision of pediatric care and support, particularly age-specific counseling, home-based

care services, and palliative care. They will also help to develop manpower and systems at local levels so that HIV positive

children can be better identified and cared for to the greatest extent possible, at the lowest and most convenient service site,

which includes the home.

The specific designation of funding for pediatric care and treatment activities in FY 2009 has helped to frame the need for and

increase attention to pediatric services. Pediatric services will be discussed during national partner meetings and treatment

partners will have specific targets to provide care and treatment to children. Home-based care providers will be expected to

employ specific strategies to increase the number of children under their care.

Funding for the NACP and Zanzibar Ministry of Health and Social Welfare (MOHSW) has been designated for pediatric activities

and will support ongoing work related to policy and guideline development, development of training programs, and supportive

supervision.

Efforts to improve infrastructure will specifically address pediatric needs. For example, care and treatment facilities constructed

through RPSO funding will include pediatric rooms, with careful attention to infection control and appropriate furnishings.

Specific partners will be tasked with discreet elements of pediatric care and treatment, to provide technical assistance to the

MOHSW, and to assist partners with implementation of harmonized practices (which has been successful in other service

elements). For example, EGPAF will take on issues related to infant identification and follow up at routine visits, and Columbia

University coordinates early infant diagnosis. Family Health International will work with NACP to include specific pediatric home-

based services in the update of guidelines.

Table 3.3.10:

The PHE "HIV Counseling and Testing to Optimize Patient Enrollment in HIV Care and Treatment" has

been approved for inclusion in the FY 2009 COP. The tracking number is TZ.08.0202.

Apri 2009 Reprogramming:

$259,966 reprogramed to IntraHealth (activity id 8663.23508.09) for a multi-country PHE and the study

design. The proposed study is a group-randomized trial, randomized at the clinic level. The study will have

three arms:

• Arm A: Enhanced provider referral to voluntary counseling and testing (VCT)

• Arm B: HTC during clinical consultation in OPD

• Arm C: HTC prior to clinical consultation in OPD

Four countries will participate in the study and each country will select 12 outpatient departments for

participation in the study. Sites will be selected using a site assessment instrument common to all countries

to ensure standardization of sites.

New/Continuing Activity: New Activity

Continuing Activity:

Emphasis Areas

Human Capacity Development

Public Health Evaluation

Estimated amount of funding that is planned for Public Health Evaluation

Food and Nutrition: Policy, Tools, and Service Delivery

Food and Nutrition: Commodities

Economic Strengthening

Education

Water

Table 3.3.14:

The PHE "Impact of Task-shifting Type II for ART Delivery on Patient and Process Outcomes in Emergency

Plan Countries" has been approved for inclusion in the FY 2009 COP. The tracking number is TZ.08.0205.

New/Continuing Activity: New Activity

Continuing Activity:

Emphasis Areas

Human Capacity Development

Public Health Evaluation

Estimated amount of funding that is planned for Public Health Evaluation

Food and Nutrition: Policy, Tools, and Service Delivery

Food and Nutrition: Commodities

Economic Strengthening

Education

Water

Table 3.3.18: