This is a continuing activity from FY06. UCSD has been working with JHPIEGO in providing site level support for hospital-based PMTCT programs in the Uniformed Services in FY06. During this period, UCSD complemented these activities by supporting the implementation of PMTCT programs at 13 hospitals in the NDFE and PFE.

The funding level for FY07 has increased from the FY06 amount, in part because UCSD has taken additional PMTCT responsibilities including training of staff in PMTCT service areas, formerly carried out by JHPIEGO, and in part because UCSD will expand services from 13 to 24 hospitals, and in part in response to recommendations from the OGAC PMTCT TA visit held in July 2006.

Their major areas of emphasis include the use of the maternal child health (MCH) platform to identify HIV-infected women and families, providing PMTCT interventions, and engaging HIV-infected patients in care and treatment. This expertise will enhance UCSD activities in Ethiopia as they expand to include PMTCT training and direct implementation of PMTCT services in COP07.

At the facility level, hospital-based PMTCT programs were initiated by MOH and JHPIEGO in collaboration with the coordinating offices for the uniform health services. In COP06, JHPEIGO provided central-level support and training on PMTCT, while UCSD supported site-level PMTCT activities, in collaboration with the MOH and coordinating offices for the uniform health services. In COP07, UCSD will add PMTCT training activities to its portfolio, expanding its activities to include training, supervision, and implementation of PMTCT programs by increasing the coverage from 13 sites to 24 sites of the Uniform Services medical centers. In COP07, UCSD will increase the quality and uptake of PMTCT services and ensure that women enrolled in PMTCT are rapidly staged and referred for care and treatment services when needed. The PMTCT intervention package will include: - Assessment of new sites, followed by development of site-specific work plans. This includes evaluation of each site's capacity to provide more advanced ART regimens, with the idea that sites should move beyond single-dose Nevirapine PMTCT regimens when sufficient capacity exists. - Immediate assessment of HIV-infected pregnant women for ART eligibility, routine CD4 testing, and provision of appropriate clinical services, including ART when indicated. - Promotion of a family-centered care model in which women are encouraged to bring their children, partners, and other family members to the facility for counseling, education, testing and care and treatment if needed. - Support for appropriate post-natal follow up of mothers and infants that will include close follow-up of infants, nutritional counseling and support, provision of prophylactic cotrimoxazole, and ongoing assessment of eligibility for ART - Tracking the supplies management required for PMTCT services. - Referral linkages between PMTCT and TB, STI, FP, and ART clinics; - Access to appropriate pre-natal care, including nutritional counseling; - Facilitation of access to IPT and bed nets in coordination with the Global Fund and other partners; - Access to nutritional education, support and "therapeutic feeding" for pregnant and breast-feeding women in the 6-months post-partum period; - Promotion of safer infant feeding, especially exclusive breastfeeding with rapid cessation when replacement feeding is not acceptable, feasible, affordable, sustainable and safe ("AFASS"); - Quality assurance by supporting staff to implement performance standards and the JHPIEGO-supported Standard-based Management Program; - Implementation of peer educator programs and support groups at selected sites; designed to maximize adherence to care and treatment among pregnant HIV-infected women, and to strengthen their links to support groups and community resources; - Provision of PMTCT-Plus training to multi-disciplinary teams at the facility level; - Support for the availability and correct usage of PMTCT registers and forms, timely and complete transmission of monthly reports to regional and central levels, and appropriate use of collected data to support quality care and ongoing performance improvements; - Supporting the Military Women's Anti-AIDS Coalition, an organization comprised of military and civilian women working toward educating and increasing awareness on HIV/AIDS and linking the PMTCT service the MARCH prevention intervention of the uniform services.

Strengthening STI Services for MARP

In FY05 and FY06, the prevention and control of STI was implemented by PEPFAR Ethiopia in collaboration with the MOH and WHO. Some of the major accomplishments during this period include, support to the revision of STI guidelines, development of STI training materials, training of providers and production of job-aids.

During COP07, UCSD will support expanded access to STI prevention and treatment services and improved quality of STI services at 43 UCSD supported uniform services health institutions in preventing new HIV infections and slowing the pace of the epidemic.

At the facility level UCSD will support provision of quality STI services at 43 health facilities. Specific activities will include: (1) Collaboration with respective uniform health services coordinating offices to conduct needs assessments at all supported hospitals, followed by joint action planning with facility staff to improve STI services and linkages between STI and other services (counseling and testing, care and treatment, ANC, etc.); (2) Provision of on-site technical assistance to improve STI diagnosis and treatment following national syndromic management guidelines; (3) UCSD will conduct training for 60 providers (physicians, nurses etc) on STI prevention, diagnosis, and treatment, with a focus on the linkages between STI and HIV infection, as per national guidelines; (4) Training of facility-based peer educators on STI prevention and treatment for PLWHA and their partners, as well as community education regarding the symptoms of STI and the need to seek care; (5) Linkages to HIV counseling and testing (C&T) services, promoting a provider-initiated, opt-out approach, for all STI patients, and linkages to care and treatment services for those who are HIV+; (6) STI education focused on risk reduction, screening, and treatment for patients enrolled in HIV/AIDS care and treatment at the hospitals, including PMTCT services; (7) Provision of condoms and education on usage to patients enrolled in care and treatment, with a special focus on most at-risk patients/populations. STI services will also be integrated into antenatal and PMTCT services to ensure that all pregnant women are educated on STI and provided with needed treatment, and are given education on STI prevention during pregnancy (according to national STI management and antenatal care guidelines); (8) Linkages to community-based organizations that promote risk reduction and HIV/STI prevention and early/complete treatment in communities surrounding UCSD supported ART sites; and (9) Supportive supervision and mentoring of clinical providers on STI services and STI/HIV linkages.

This is a continuing activity from FY06. It is programmatically linked to the following activities: access to home water treatment and basic hygiene counseling (6630), promote positive living and self reliance for HIV/AIDS affected beneficiaries of urban nutritional support program (New-1061), Improving HIV/AIDS/STI/TB Prevention and care activities (5635), Uniformed Services PMTCT Implementation Support - Hospital Level (5638), HIV/AIDS program implementation support (5676), military ART support (5666).

In FY06, UCSD introduced a basic palliative care approach to the six ART facilities it supports; this included initial assessment of the palliative care activities at sites, development of site level training in collaboration with the national lead, and supervision of palliative care activities. Training and supervision focused on identification of pain and discomfort among HIV patients, ensuring cotrimoxazole prophylaxis, TB screening and targeted elements of the preventive care package such as multivitamin use, nutritional assessments and prevention for positives. This program was introduced to six Uniformed Services hospitals.

In FY07, UCSD will support palliative care activities at 40 Uniformed Services hospitals providing HIV/AIDS care and treatment, via a multi-disciplinary, family-focused approach to provision of the preventive care package both for adults and children. This approach will incorporate best practices for the health maintenance and prevention of opportunistic infections for people with HIV infection, to slow disease progression and reduce morbidity and mortality.

At the facility level, UCSD will assist the uniformed service hospitals to provide the preventive care package, complementing Global Fund, MOH, and other USG-funded activities when possible. UCSD will focus on provision of the preventive care package which, for adults, includes: active TB screening, cotrimoxazole prophylaxis, symptom management, micronutrient (multivitamin) and nutrition supplement and counseling, provision of insecticide mosquito nets (linkage), positive living, HIV counseling and testing of family members and contacts, and assisting safe water through provision of safe water vessel at all UCSD supported hospitals. The preventive care package for children includes: prevention of serious illnesses like PCP, TB and malaria, prevention and treatment of diarrhea, nutrition and micronutrient supplement and linkage to national childhood immunization programs. Orphans and vulnerable children (OVC) will be prioritized for palliative care and linked to other OVC care programs to receive a continuum of care.

UCSD will work closely with other university partners to ensure complementary activities. More details on the delivery of these aspects of the preventive care package are outlined below.

UCSD facility-level support will be continued or expanded as follows:

1. Strengthen internal and external linkages required to identify HIV+ individuals and provide them with access to care. Internal linkages include referrals to the HIV/AIDS/ART clinic from ANC, TB clinic, under-5 clinics, inpatient wards, OPD, and VCT. External linkages include referrals to and from community-based resources providing counseling, adherence support, home-based care, and financial/livelihood and nutritional support. 2. Provide on-site implementation assistance, including staff support, implementation of referral systems and forms, and support for monthly HIV/AIDS team meetings to enhance these linkages. 3. Provide training on palliative care/the preventive care package to multi-disciplinary teams. 4. Provide clinical mentoring and supervision to multi-disciplinary care teams related to care of PLWHA, including those who do not qualify for or choose not to be on treatment. Provider job aids and patient education materials related to palliative care and positive living will continue to be developed and distributed. 5. Improve nutrition assessment at a health facility level 6. Intervention (pharmacologic/opioids and non-pharmacologic) to ease distressing pain or symptoms. 7. Continued management after hospital discharge if pain or symptoms are chronic. 8. Linking with community resources after discharge.

UCSD's support activities will promote OI prophylaxis and treatment in accordance with

national guidelines. Appropriate use of Cotrimoxazole prophylaxis (pCTX) is an essential element of care for HIV+ patients, and for HIV-exposed infants, and will be an important component of UCSD's implementation activities, especially at sites not yet providing ART. UCSD will ensure that all supported sites have reliable stocks of cotrimoxazole tablets and syrups, providing emergency supplies when absolutely needed to ensure quality and continuity of care. Similarly, TB screening and isoniazid prophylaxis will be promoted and provided for HIV+ adults and children. (See also the activity section on TB/HIV activities). Supportive supervision and the institution of standard operating procedures will enhance the use of cotrimoxazole and INH prophylaxis. Attention will be given to the issue of HIV/malaria co-infection, and provision of impregnated bednets routinely to pregnant patients at the HIV/AIDS and PMTCT programs in collaboration with Global Fund.

Health education and behavior change communication for HIV-infected individuals will be provided by facility and lay staff, complementing Global Fund and other USG-funded activities where they exist. Patients will have access to nutrition counseling and multivitamins. With guidance from JHU, the university lead for hospital-level nutrition, "therapeutic feeding-by- prescription" of patients who qualify based on criteria agreed upon with PEPFAR (e.g. HIV+ pregnant or lactating women, HIV exposed or infected infants who are no longer breast feeding, malnourished patients) will be provided in at least 5 hospitals. Clear criteria will be established for patient selection, and ‘exit' strategy development will be part of all initiation of therapeutic feeding support. Health education, counseling, and support will encourage positive living to forestall disease progression, promote prevention among positives to prevent further HIV transmission, and enhance adherence.

UCSD is collaborating with the training and evaluation program of San Diego Hospice, internationally known for its expertise in palliative care delivery, training, and evaluation. In FY07, UCSD will take the lead among the US university partners in the area of opioid use and education. Activities will include: 1. Providing technical assistance to a HAPCO Task Force (that includes Ethiopian and international experts and clinicians) to develop a MOH Policy on opioid use and education. 2. Developing specific sub-indicators for the palliative care delivery so that the domains of suffering are being specifically assessed. 3. Expanding the demand for and understanding of PC through education of the public and especially ART recipients. Specifically, UCSD work with PLWHA to train patients and providers on the value of pain management as a way of increasing quality of life. Additionally, UCSD plans to initiate peer support groups within the uniformed services s to address pain management, and will promote experience sharing through available military and police media.

This activity also relates to activities in Counseling and Testing (#5737), ART (#5666), Palliative care (#5770), and PMTCT (#5638).

Proposed activities will build on existing activities and plans for TB/HIV in Ethiopia.

UCSD has been providing TB/HIV support to the National Defense Force (NDFE) and Police Force since 2006. In 2006, UCSD increased its technical support from 6 sites to 13 sites.

Working with other US universities, UCSD has implemented a package of interventions, including (1) expansion of provider-initiated HIV counseling and testing for TB patients, (2) referrals of HIV+ TB patients for HIV-related care including CTX and ART, (3) TB screening in HIV care and treatment settings, and (4) isoniazid preventive therapy (IPT) for HIV+ patients. The Armed Forces Teaching General Hospital (AFTGH) is one of the original nine TB/HIV pilot sites, thus lessons learned from this site are used to improve activities in other facilities.

Expanding capacity for TB/HIV has followed a phased approach in 2005 and 2006 with the initial focus on the three referral centers, followed by the five smaller regional hospitals in phase 2, and the smaller division medical centers in phase 3. The next phase, in 2007, will be to include all the peripheral hospitals and clinics served by the uniformed services. These will include regional clinics as well as peripheral health centers.

In 2007, UCSD intends to continue and enhance the TB/HIV program by increasing its technical assistance to 43 sites. Some of these (19) will not provide ART, but all will have HCT capacity. UCSD will specifically be supporting the uniformed services in the areas of (1) TB/HIV clinical co-management, including ART, (2) adaptation and implementation of TB infection control strategies in hospital settings, (3) renovation of physical space and lab infrastructure for TB/HIV activities, and (4) improvement in medical informatics for health data management and information systems.

UCSD plans to further expand the TB/HIV program through: (1) Awareness campaign for TB/HIV using military and police media services, (2) Strengthening follow-up of TB/HIV patients through case managers and PLWHA/TB, (3) Support PLWHA/TB to form peer support groups, (4) Collaborate with ENHRI to evaluate the sensitivity of isolates of mycobacterium tuberculosis to antimicrobial agents, (5) Assessing adherence to INH prophylaxis of HIV patients.

The following indicators will be used to monitor the program (1) Number of HIV+ clients from VCT/PMTCT/ART clinics screened for TB (2) Number and percentage of TB patients recorded to be HIV+ (3) Number and percentage of registered TB/HIV patients accessing ART for the reporting period (4) Number and percentage HIV/TB accessing CTX for the reporting period

CT Support at Uniformed Services Hospitals and Clinics

This is a continuing activity from FY06. In FY06, I-TECH supported HIV counseling and testing services in 13 ART Military and Police hospitals; this included an initial site assessment, site level training in collaboration with JHPIEGO, minor renovation, improving data collection and reporting, and supervision of counseling and testing services. Six additional sites are on preparation to initiate VCT services. The site level support aimed at improving performance to deliver quality HIV Counseling and testing services for the uniform personnel and families. The partner is on track according to the original targets and workplan. We have increased funding based on the achievements from partially FY06. This activity is linked to COP ID # 5770 and 5752 (palliative care basic and TB/HIV) and COP ID 5666 (treatment: ARV Service).

During COP 06, Counseling and Testing (CT) programs in the Uniformed Services were continued through collaboration between UCSD and JHPIEGO, who provided training and technical support to CT programs. During this period, UCSD complemented these activities by supporting the implementation of CT programs at 13 hospitals in NDFE and Police forces. Overall the scope of assistance in collaboration between the NDFE and UCSD will focus on (1) site level training of counselors in relevant skills, capacity building, staff educational programs, and outcomes assessment; (2) Laboratory enhancement of capacity for HIV-testing and quality assurance; (3) drama and advertising through military and media, in collaboration with the CDC March programs in the defense and police forces

Major interventions by UCSD related to counseling and testing have been in: (1) Adoption of provider initiated CT (PICT) and opt-out strategies for CTR hospital and outpatient clinic settings; (2) Assessment of current capacity for care, laboratory testing, and nursing support of VCT; (3) Support for the sites to provide a one hour HIV testing at VCT sites; (4) Strengthening of the referral link between counseling and testing with post test services. (5) Supported site level refresher training and mentoring for HCT personnel through UCSD experts; (6) Support for minor renovation of physical space to ensure privacy, test kits and lab supply; improvement of data management system of CT and reporting; (7) Establishment of a quality assurance system for counseling and testing service for both client and provider initiated HCT.

In 2007, UCSD will take over all activities related to HCT including technical support and training for health care professionals working in the Uniformed Services. Additionally, UCSD's reach will increase from 13 to 43 sites, all of which will have HCT capacity thereby facilitating the provision of counseling and testing services to remote peripheral regions. To expand and enhance this program in 2007, UCSD will establish regular trainings, assessments and mentoring of HIV counseling and testing military providers and supporting lab workers through both local staff and visiting UCSD experts. UCSD started this program at the larger referral military and police hospitals and has systematically expanded it to the regional military hospitals and police clinics. UCSD will continue its support in 2007, gradually increasing the reach of counseling and testing at the regimental level and by supporting the military's mobile VCT services, at the regional clinical level in the police and also by providing CT at all prison sites (prison guards and prisoners) around the country.

UCSD plans to further expand the CT program through: (1) Consolidating the existing VCT and Provider Initiated Counseling & Testing services to increase the uptake of individuals receiving counseling and testing in health care settings. UCSD will initiate counseling and testing service in new additional 33 sites. Also ensure families members including children access counseling and testing. (2) Collaborating with the CDC March Program for outreach education, drama and advertising. The sites will be supported to provide outreach counseling and testing services to uniform personnel and families. In collaboration with PEPFAR -E will organize a mobile service for hard to reach camps in periphery of the country. (3) Involving PLWHA as peer advocates for HCT and ART promotion and peer support for positives. Peer support groups and experience sharing through uniformed services media

(4) Conducting site level basic and refresher training on VCT and PICT for service providers and will pilot non health professional uniform personnel to conduct counseling and testing services. (6) Facilitating the establishment of peer counseling supervision system to assure quality of HCT service. (7) Improving monitoring and evaluation system and timely reporting of data in all sites through training and mentoring of the staffs. (8) Working with prison administration at Federal and Regional level UCSD will support to strengthen HCT services in prison clinics.

All activities will be closely monitored by I-TECH regional office staff and central office Clinical Advisors. The university will support to strengthen administrative and technical coordination mechanism to improve the management system of the service. The activity will help to reach PEPFAR Ethiopia target for care and treatment. PLUS UP FUNDING: "PEPFAR E will expand HIV Counseling and Testing (HCT) services among uniformed service personnel and in prisons using facility-based stand-alone and mobile HCT services. The University of California at San Diego (UCSD) will work closely with the Department of Defense (DOD) to expand VCT in existing military health facilities to regiments and battalions. Civil-military collaboration is an essential aspect of HIV prevention and care. In addition to sharing the common goal of reducing the spread and impact of HIV, the military sector in Ethiopia has great experience of the problem which it can share.

" "It can provide facilities, such as counseling and care, which are not always readily available in the civilian community in remote areas and emerging regions; sharing scarce resources and expertise reduces the burden on both sectors. The civilian communities around uniformed services establishments are potentially targeted, particularly high risk groups such as FSW, migrant mini traders and other mobile populations. There is limited data on HIV prevalence in Ethiopian prisons; however there are efforts at the Federal prison to create awareness among prisoners and officers and to provide VCT within prison health services.

" "Through the plus up fund, UCSD will upgrade military health facilities, five federal and eleven regional prisons to provide VCT, establish mobile units, train service providers, conduct needs assessment, provide supportive supervision, improve data management system, logistics including test kits. Mechanisms to link HIV+ clients automatically to care and treatment services will be created. There is limited data on the prevalence of HIV in the Ethiopian prison. " Through the plus up fund UCSD will upgrade military health facilities, five federal and 11 regional prisons to provide VCT, establish mobile units, training of service providers, conduct needs assessment, give supportive supervision, improve data management systems and logistics including test kits. Mechanisms to automatically link HIV+ clients to care and treatment services will be created.

Military ART Support

This is a continuing activity from FY05, FY06 and relates to activities in Counseling and Testing (5737), TB/HIV (5752), Palliative Care (5770), and PMTCT (5638), STI Services (1044), Laboratory Infrastructure (new) as well as activities implemented through the Twinning Initiative (5678).

UCSD has played a critical role as the lead for Military-Public Alliance and has supported implementation of ART in Operation Zone 4 (Defense and Police forces). Partner is currently well on track in meeting targets for COP06.

National Defense Forces of Ethiopia (NDFE), the Federal Police of Ethiopia (FPE), and the Ethiopian Ministries of National Defense and Health, and the Federal Prison Administrations (FPA) have committed to building capacity to care for and to provide free ART to their members.

PEPFAR Ethiopia provides the support to build on an ongoing collaboration between NDFE and physicians at the University of California, San Diego. Since 2005, UCSD, in cooperation with I-TECH, has assisted the NDFE, FPE and FPA with (1) assessment of current capacity for clinical care, laboratory testing and nursing, and pharmacy support of ART; (2) training and mentoring for clinical, laboratory and infection control personnel through regular conferences in each facility or via tele-conferencing with UCSD experts; (3) support for physical space and equipment and reagents; and (4) improvement in medical informatics for health data management and information systems.

In 2006, UCSD established a program of site assessments and of training and mentoring of military physicians, health officers, nurses, lab workers, and pharmacists to support rapid expansion of ART. UCSD has hired the necessary staff to enable sites to deliver ART services. UCSD's technical support to the sites has included on site mentoring and monitoring of ART activities during regular follow up visits. Additionally, UCSD has ensured intensive and efficient support of ART activities for the large military populations along the northern border with Eritrea by stationing a team of expert ART trainers in Mekele.

After UCSD local staff and visiting experts trained medical staff at the three Military and one Police centers in Addis Ababa during 2005 and early 2006, the activity systematically expanded to the regional military hospitals and police and prison clinics, totaling 13 facilities in 2006. UCSD will increase its technical support from 13 sites in 2006 to 43 sites in 2007. These sites will be, for the most part, major hospitals, 24 of which will have ART (as well as HCT) capacity, and the remainder will be regional clinics and health centers that will only have HIV counseling and testing (HCT) capacity.

In order to ensure sufficient trained manpower for its rapid expansion of sites, UCSD has partnered with the Defense University Health Science College to build capacity through pre-graduate and postgraduate training. In 2006 UCSD began to provide technical assistance to the Defense Health Science College for revision of its curriculum for health officers and nurses and provided intensive courses in HIV medicine to health officers and nurses immediately post graduation.

To improve coordination and integration of the program with the military and police administrations, UCSD has provided workshops for high-ranking non-medical military, police and prison administration leaders to familiarize and involve them in our programs of prevention and treatment. UCSD has worked with PEPFAR partners to raise awareness of availability and utility of HIV/ART services through media controlled by the uniformed services.

UCSD's assistance in 2007 will expand in a number of directions: (1) New ART and HCT sites will initiate services for staff and prisoners of the Federal Prison Administration (FPA), military and regional police clinics. (2) Protection of medical personnel from occupational HIV exposure - the risk of HIV transmission from occupational exposures to blood borne pathogens (HIV and HCV) in HCW is low, but contributes to HCW reluctance to provide HIV care in Ethiopia.

(3) Training for undergraduate and newly trained medical personnel - UCSD will continue our program for improving undergraduate medical education for physicians, health officers, pharmacists, and nurses needed to expand ART deployment. This will include supporting HIV training in their curricula and intensive practical HIV training and experience. (4) Involvement of reservists - the NDFE has a training program for army reservists whereby, tens of thousands of personnel are trained annually then returned to their home kebeles where they provide reserves for the regular forces. Because they are respected community members/leaders, UCSD and Ethiopian military leaders agree that training these reservists to become community-based peer leaders for HIV/AIDS issues would be feasible and have wide geographical impact. This will be implemented with other partners and stakeholders and will constitute a part UCSD's public-military partnership initiative. (5) HIV education for non-medical uniformed trainees - UCSD will implement educational programs for students in the other, non-medical Defense University College Schools such as the School of Engineering and the Cadet School and Police training sites. These programs will prepare them to protect themselves and be effective future leaders in the integration of HIV prevention and care into their institutions. (6) Support for the Military Women's Anti-AIDS Coalition - this organization, which is comprised of military and civilian women working toward educating and increasing awareness on HIV/AIDS, can increase outreach to the women in the uniformed communities. UCSD will assist in developing programs to address issues of gender- and age-related inequity in access to ART by empowering women as patients or wives and mothers of HIV+ patients. (7) Provide technical assistant to establish a family-centered treatment and care model and support the implementation of a pediatric treatment and care package. (8) Media campaigns to promote ART - UCSD will support media campaigns that target military and police personnel to advertise the utility of ART and reduce HIV-related stigma. (9) Support of PLWHA and others as peer advocates for ART - UCSD will help to organize and support military unit and hospital/clinic based support groups to provide care, psychological support, and peer advocacy (please see narrative on PLWHA Involvement). (10) Informational support for non-medical uniformed personnel - creating an anonymous telephone hotline for military personnel through the military communication system and facilitating access to the civilian HIV hotlines for prison inmates and federal and regional police members.

UCSD will assist the ART health networks to follow standardized clinical procedures and use of tools, agreed upon by all partners, providing technical support to the country. In its lead area of training, military-civil alliance in ART delivery, UCSD will coordinate joint planning and implementation.

Monitoring of HIV viral load and Drug Resistance in ART patients

This assessment will monitor the effectiveness of ART in a selected patient population receiving ART using sentinel viral load and drug resistance. This will be achieved through the following activities: (1) determination of the rate of HIV drug resistance in ARV treated patients who have sub optimal CD4 cell count response (defined as < 50 cells/ mm3 increase from baseline after more than 6 months of ARV); (2) determination of the rate of virologic failure (HIV RNA > 400 copies/ mL) in ARV treated patients with sub optimal CD4 response; (3) description of the pattern of genotypic mutations in Ethiopian patients, most of who have clade C virus, with treatment related drug resistance and compare the patterns to clade B virus treated historical control patients; and (4) determination of the factors associated with HIV drug resistance among ARV treated patients who have suboptimal CD4 cell response, which include: age, sex, ethnicity, viral clade (if any are non-clade C), pretreatment CD4 count, history of treatment related toxicity, adherence (self reported and based on pharmacy records) and HIV disease stage.

HIV drug resistance occurs in more than 75% of ARV- treated patients who develop virologic failure to one or more regimens. The first step in defining drug resistance is identifying patients with virologic failure and then performing drug resistance testing. Assessing the prevalence of HIV drug resistance in Ethiopia is complicated by the relative scarcity of HIV RNA and genotype drug resistance testing. Since therapy decisions are guided by CD4 cell count response and immunologic failure is a late consequence of virologic failure (up to several years later), alternative strategies are needed to monitor development of drug resistance. This TE targets a population of patients at higher risk for virologic failure and drug resistance, those who fail to gain more than 50 CD4 cells/ mm3 after 6 months of therapy. In addition to determining the prevalence of virologic failure and drug resistance, this TE will evaluate factors associated with drug resistance in order to inform future monitoring efforts and target therapeutic strategies to limit drug resistance.

This is a prospective, cross- sectional observational cohort study designed to determine the prevalence and risk factors of virologic failure and HIV drug resistance among ARV- treated Ethiopian general and uniformed service patients. Resistance and virologic failure will be evaluated in a subgroup of patients who experience suboptimal CD4 cell count recovery. Suboptimal CD4 recovery is defined as gain of less than 50 cells/ mm3 from initiation of therapy for those who have received at least 6 months of continuous treatment. Studies in resource-constrained settings have shown that a gain of at least 50-cells/ mm3 is a sensitive (but not specific) predictor of having HIV RNA < 500-copies/ mL. A gain of < 50 cells/ mm3 was significantly associated with having a detectable HIV RNA value. Thus, selecting patients with suboptimal CD4 count gains (or those who initially had more robust CD4 increases and subsequently had decrease to < 50 cells) will be more likely to identify those at risk for virologic failure and drug resistance.

Patients will be identified from public and military hospitals and health centers. Records from the ARV clinic will be reviewed to identify patients who meet clinical and laboratory criteria for entry and these patients will be sequentially offered entry into this TE. The TE will be explained and consent obtained prior to any study procedures. After consent, subjects will have a single blood draw of 20 mL in EDTA tubes. Samples will be transported to the EHNRI HIV Reference Laboratory where specimen processing and storage will be accomplished. Approximately five 2-mL aliquots of plasma will be stored at -70 C for batch testing, ideally within 6 hours of blood draw.

Data will be collected from each subject using the Advanced Clinical Monitoring (ACM) forms. For patients already enrolled in the ACM cohort, data will be electronically extracted from the local ACM database. For those not in the ACM cohort, data will be entered into a MS SQL database, using an Access front end, provided by the UCSD team. The UCSD team will also provide data management, quality assurance and training. The clinical data will be merged with laboratory data including the HIV genotype resistance assays. UCSD will provide a database to capture and store HIV genotype data at the cordon level (i.e. FASTA files will be uploaded into the database from the genotype output from the laboratory obviating the need for entry of this data). Clinical data elements will include: age, sex, ethnicity, viral clade (if any are non-clade C), pretreatment CD4 count and serial CD4 count information, treatment regimen, history of treatment related toxicity, adherence

(self reported and based on pharmacy records) and HIV disease stage

A random sample of 10-20% of these populations, approximately 1,000-2,000 patients (after 6-12 months being on ART) will have sentinel viral load determination. End-point will be undetectable viremia. The proportion of detectable viral load will be determined to evaluate treatment failure rates either due to adherence or real virological failure. Those with virological failure will have genotyping for ARV drug resistance. Samples that have HIV RNA values > 500 copies/mL will be tested in batch for HIV genotype including the reverse Transcriptase and protease genes .The targeted evaluation will include a control group of patients treated by physicians at hospital level to compare the difference in the provision of ART service at the two tiers of health care service.

The targeted evaluation proposed will be implemented in partnership with Hadassah University, EHNRI and PEPFAR Ethiopia. UCSD, as a prime partner, will allocate 45% of the fund to Hadassah University. A joint and detail project proposal will be worked out by both UCSD and Hadassah University in consultation with EHNRI. As part of the sustainability and continuity of drug resistance monitoring and genotyping, this activity will be linked with the establishment of the technology at the National HIV Laboratory, EHNRI.

Site-level laboratory Support

In FY 2006 this activity was provided by CDC. As most activities are becoming regionalized in 2007, UCSD will assume this activity for the uniformed services. For 2007 this activity is not being considered a new initiative, but rather a continuation of a 2006 activity.

Scale up of quality ART depends on quality laboratory services. UCSD's 2007 COP encompasses laboratory support activities needed at sites for scaling-up ART, VCT, PMTCT and TB services.

In 2007 supportive activities will include the following four activities.

(1) Assessment of the lab capacity of the sites with regard to the number and educational level of lab personnel at all the sites; training needs of the lab personnel for both primary and refresher and advanced courses; capacity for testing relevance to HIV care and treatment including hematology and chemistry, CD4 counts, diagnostic tests for HIV (rapid tests and ELISA), TB (smears for AFB), and STI (syphilis serology and stains for gonococci) and viral load testing in the central referral hospital; and accuracy and functional status of lab equipment.

(2) Improving laboratory availability and quality through primary and refresher and advanced training courses in assay methods and equipment maintenance supplemented by on-site training and mentoring in collaboration with EHNRI and regional laboratories; ensuring a reliable supply of lab reagents; safe handling and transportation of specimens; employment by UCSD of trained experts who assist sites with identification and trouble shooting of logistical problems in supplies and equipment and serving as liaison between sites and laboratory experts at national level.

(3) UCSD will technically assist in laboratory services; specimen collection at health centers or peripheral hospitals and transport to next hospital laboratory and regional laboratory for diagnosis and monitoring ART; and provide technical support in specimen collection, transportation, patient sample tracking, reporting of results and implementing standard guidelines and procedures.

(4) On-site visit and technical assistance to site laboratories will include laboratory management, internal re-organizational lab set up, specimen management, test procedures, documentation, reporting, and inventory management, and inventory and stock management of laboratory supplies at each health facility.

Site Level Data Support among Armed Forces Health Facilities

This is new activity for FY07. This activity relates and linked to other program areas including counseling and testing, TB/HIV, palliative care, PMTCT in addition to ART services. This activity will also be strengthening the implementation of the national HMIS.

The MOH has established a chronic disease record-keeping system for the national ART program. Standardized tools include intake and follow up forms, pre-ART and ART registers, monthly cohort analysis and reporting forms among others. The national ART monitoring and evaluation system provides the means to collect data in a standardized manner. However, data at site level is currently under-utilized.

The ART program would be strengthened further by increasing the capacity of treatment-providing hospitals, central defense as well as command health departments and defense health science colleges to collect, manage, analyze and utilize ART-related data generated at site level for decision making to improve clinical and program management.

PEPFAR Ethiopia is planning to expand provision of comprehensive HIV/AIDS services to 131 civil and uniformed services hospital networks in FY07. Despite the rapid expansion of HIV/AIDS services all over the country very little attention was given to systematically analyze, document and share the information by stakeholders at all levels (i.e. health care personnel at facility level, health managers at division and command level). Therefore, limited information is available on the quality of services, barriers to utilization of services, and documentations on best practices in PMTCT, HCT, TB/HIV, palliative care and ART services.

UCSD will provide technical support to 43 hospitals in the uniformed services and the two health science colleges in the NDFE and the Federal Police Force to assess and monitor HIV/AIDS services coverage, quality and process. In addition, UCSD will support development of data collection systems streamlined to capture required data for calculation of standard indicators.

Data use will be supported at all levels to enable them to manage data and use data. Sites will be further enabled to appropriately tabulate and visualize their data such as the use of GIS, tables, charts, line and bar graphs and other standard methods. Appropriate options for tabulation include aggregation of data by patient, clinic and command levels.

Specific activities include training of health care providers at facility level in basic computer skills and data management which includes data entry, data analysis, paper writing and presentations, provision of technical support to staff at facility level as well as command heads to systematically collect, analyze and document service related data. The support to the sites will strengthen the national M&E system the MOH/HAPCO and regions are developing with other PEPFAR Ethiopia funds. UCSD will also support documentation of best practices and presentations of findings and experiences both at local and international scientific and programmatic forums for priory setting and decision making.

Implementation mechanisms for this activity will include providing the necessary modeling at site and command levels within the uniformed services.