Protecting Families Against HIV/AIDS (PREFA) is a Non-Governmental Organization promoting

comprehensive, PMTCT activities in Uganda. PREFA has core PMTCT activities and supports two sub-

partners, Tororo District Hospital (TDH) and Islamic Medical Association of Uganda (IMAU). In FY 2006,

PREFA and its sub-partners supported PMTCT implementation through 16 outlets (three hospitals, five

health center (HC) IVs, four HC IIIs, four HC IIs) in four districts, leading to provision of HIV counseling and

testing [HCT] to 37,935 pregnant women and identifying 3,589 HIV+ women. In FY 2007, PREFA will

provide PMTCT routine HCT to 313,569 pregnant women in 26 districts (including 22 new districts) through

150 outlets, serving an estimated 23,919 HIV+ pregnant women. In FY 2008, PREFA and its sub-partners

will further expand support of comprehensive PMTCT services to two new districts bringing the number of

supported districts to 28, providing HCT to an estimated 367,621 pregnant women and serving an estimated

27,785 new HIV+ pregnant women. Provision of comprehensive PMTCT services will include the four pillar

approach: primary prevention, family planning, provision of ARV prophylaxis, and care and support.

In FY 2008, PREFA's core targets, without its sub-partners, will be 348,621 pregnant women, and their

families. The districts supported by PREFA will aim at intra-district scale up with transition to static HCT

services for pregnant women at HC II. Clients will receive a comprehensive PMTCT package including opt-

out routine HCT at all Maternal and Child health units (MCH). All HIV+ pregnant women, estimated to be

23,088 will receive a basic care package (BCP), their blood samples be taken for CD4 testing, and ARV

prophylaxis and treatment for HIV+ mothers and their babies will be provided according to national revised

PMTCT policy as follows: about 2,309 (10%) women who present for antenatal care and are eligible for

ART will receive HAART; 11,544 (50%) will receive combined ARV prophylaxis and 9,235 (40%) will receive

SD NVP, and infants will receive NVP or AZT syrup accordingly. Midwives in MCH units will be trained to do

HIV clinical staging and provide the appropriate ARV prophylaxis, or actively refer clients to the nearest

ART clinic. All ART clinics will prioritize HIV+ pregnant women for screening and ART provision. In addition,

quality obstetric care (focused antenatal, maternity, and post-natal care) will be provided for HIV+ mothers.

PREFA will facilitate partner districts to establish or strengthen links between existing ART implementing

partners (IPs) and PMTCT sites to manage referred pregnant women. Family planning (FP) will be provider-

initiated for all adults presenting at all health facilities up to HC III. FP will be strengthened in ANC and

postnatal services, through provision of personnel and close supervision by the districts, emphasizing

postnatal clinics and HIV+ women. Early infant HIV testing with enhanced counseling will be integrated

according to policy guidelines. All mothers of babies presenting at postnatal and young child clinics will be

counseled to test for HIV (if not done and documented before delivery), to know their status and assess if

their babies are exposed to HIV. Blood specimens (DBS) will be taken from all HIV exposed infants and

tested using DNA-PCR at the nearest diagnostic Centers.

PREFA will support district health officers and their teams to strengthen reproductive health systems to

ensure quality PMTCT services, in collaboration with relevant agencies in each district. Their activities will

include strengthening of human resource capacity through training and/or re-orientation of existing staff

(PMTCT and infant feeding counseling course and PMTCT policy updates for 1,635 health workers, and

training of 50 trainers/supervisors in PMTCT in the 28 districts), supporting districts to hire additional staff in

areas where it is critical such as pediatric care and counseling, FP, home-based HCT, and community

awareness and mobilization. District health teams will support improvement of facilities to accommodate

such additional services as routine HCT. PREFA will also provide technical support for procurement, and

funds for activities agreed upon at district level; strengthen the PMTCT care, support referral linkages within

and between facilities, and the community. The organization will support mechanisms for enhancing

PMTCT service delivery through private and government health units (public-private partnership)

collaboration, including sensitization of traditional birth attendants (TBAs) and private midwives in PMTCT to

enable them identify and refer HIV+ women to deliver in health facilities. Districts will be facilitated to

improve monitoring and evaluation capacity through training in data management, providing computers as

needed and other forms of data processing and storage, ensuring timely reporting from health facilities to

districts/ Ministry of Health (MOH) and PREFA. Districts health teams will also conduct regular monthly

supervision of health facilities, and quarterly supervision by MOH and/or regional supervisors.

Additionally, PREFA supported districts will strengthen their community PMTCT activities using existing

structures - health workers, PHA, Community Based Organizations (CBOs), and community resource

persons (VHT, CCAs and TBAs). These groups will receive relevant training in PMTCT to enable them

mobilize, sensitize, counsel and refer appropriately; and will follow-up an estimated 12,000 family members

identified by the counselors at health facilities offering PMTCT, as well as referring clients and immediate

family members to other partner institutions for further care.

PREFA will liaise with the MOH and other stakeholders to disseminate updated training materials, and

appropriate community IEC materials for PMTCT. Further more, PREFA will assess the performance of the

two-year Family Care Consortium program that has been running at two peri-urban health facilities in

Kampala, aimed at improving access and uptake of quality comprehensive HIV/AIDS services for Families.

In addition to the activities above, sub-partner TDH will support provision of PMTCT services to 16,500

clients and 3,300 of their male partners, provide ARV prophylaxis to 1,600 HIV+ pregnant women, early

infant testing for 840 children at 11 other health facilities up from eight in FY 2007. Health teams will

conduct home visits to 3,000 HIV+ pregnant/nursing mothers, carry-out 480 home based HCT to increase

access to HIV services by family members, provide the BCP, and refer clients and family members for

further care/treatment to TASO - Tororo and TDH ART clinics. Funding will also support training of 45

health workers in pediatric care, rapid HCT, procurement of test kits, lab equipment, reagents and supplies,

therapeutic feeding of 240 infants, and nutrition classes for all enrolled HIV+ mothers. The program will also

introduce Community support teams of 100 members (including 50 TBAs) who will mobilize the community

for PMTCT and monitor its contribution to service delivery. Community sensitization will continue through

monthly radio talk shows, drama by HIV/AIDS support groups, and community video shows. The Tororo

Child Cohort (TCC) study, a collaboration between CDC-Uganda, TDH, PREFA, Makerere University Univ.

of California San Francisco collaboration (MU-UCSF) and TASO-Tororo, will continue to run in FY08.

Additionally, in FY 2008 IMAU, the other sub-partner, will continue to provide comprehensive PMTCT

services at Saidina Abubakar Islamic Hospital (SAIH) and at HC IVs and IIIs in Wakiso district. SAIH will

provide PMTCT services to 2,500 pregnant women and 1,200 of their male partners, provision of ARV

drugs for PMTCT to 310 HIV infected mothers and their infants; CD4 tests for all HIV+ women and ART to

Activity Narrative: eligible women and their partners. PCR tests will be done for 180 exposed infants. IMAU will conduct

community education and mobilization that target 30,000 adult men and women, and PLHAs, using health

fairs, outreaches, and home visits. The project will provide community follow up services to 4,500 pregnant

women and their families. This funding will also support purchase of HIV test kits, ARV (for PMTCT),

equipment, logistics and supplies, and training of 30 service providers in PMTCT counseling.

Overall, PREFA and its sub-partners will contribute to PREFA's vision of improving access to high quality

HIV/AIDS services using a family approach, through provision of PMTCT services. In FY08 this program will

reach an estimated 367,621 pregnant women with HCT services, identify and provide ARV prophylaxis to

an estimated 24,998 HIV+ women and their infants, as well as appropriate referral for treatment, care and

support services.

This activity is a continuation from FY07.

Title of study: INTERACTIONS BETWEEN HIV AND MALARIA IN AFRICAN CHILDREN: TORORO CHILD

COHORT (TCC) STUDY

This study is a collaboration between CDC-Uganda, Tororo District Hospital (TDH), Protecting families

against AIDS (PREFA), Makerere University Univ. of California San Francisco collaboration (MU-UCSF),

The AIDS Support Organisation (TASO) Tororo and the Univ. of Washington.

Time line and budget summary:This request is for the second year of activity. Funding was approved in

FY06, IRB approval was obtained in May 07 and enrolment started in July 07Expected year of completion is

2009.

$145,280 have been received to date from PEPFAR and another $110,000 has been contributed by MU-

UCSF. A similar total amount is needed for completion (including FY08 request).

Local investigators:

Principal Investigators: Jordan Tappero, MD, MPH, Principal CDC Investigator; Grant Dorsey, MD, PhD,

Principal UCSF Investigator; Moses R. Kamya, MBChB, MMed, MPH, Makerere University (MU) Principal

Investigator

Local Co-Investigators: Anne Gasasira, MBChB, MPH, MU; Taylor Sandison, MD, DTM&H, MU-UCSF and

Univ. of Washington; David Moore, MD, MPH, CDC-Uganda; Jaco Homsy, MD, MPH, CDC-Uganda

Project description:

This is a prospective cohort study where HIV-infected and uninfected children are being enrolled between 6

weeks and 9 months of age and followed to the age of 21 months. All HIV-infected children are given

trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis as of 6 weeks of age. HIV-uninfected children born

to HIV-infected mothers are given TMP/SMX prophylaxis for the duration of breastfeeding and then

randomized to continuation of TMP/SMX or discontinuation of TMP/SMX prophylaxis. HIV-uninfected

children born to HIV-uninfected mothers will not be given TMP/SMX prophylaxis. Study participants will be

followed for all of their health care needs in a designated study clinic. All mother-child pairs receive a basic

care package including insecticide-treated bednets (ITNs) at enrollment. All HIV-infected mothers and

children are receiving antiretroviral therapy if eligible according to standardized WHO criteria. Study

participants 4 months of age or older and at least 5 kg are being randomized to treatment with artemether-

lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) at the time of their first diagnosis of uncomplicated

malaria. Study participants will receive the same antimalarial treatment regimen for all future episodes of

uncomplicated malaria. Study participants less than 4 months of age or less than 5 kg diagnosed with

malaria and all episodes of complicated malaria will be treated with quinine in accordance with local

guidelines.

We are testing the hypotheses that:

1.TMP/SMX prophylaxis is highly effective in preventing malaria in both HIV-infected and HIV-uninfected

children

2.The use of TMP/SMX prophylaxis is associated with an increased risk of infection with malaria parasites

containing antifolate resistance-conferring mutations.

3.The use of ARV drugs is associated with a decreased incidence of malaria.

4.The efficacy, safety, and tolerability of AL and DP for the treatment of uncomplicated malaria differ.

Participants and sample size:

400 children will be enrolled in the study: 100 HIV-infected children will be given TMP/SMX prophylaxis, 200

HIV-uninfected children born to HIV-infected mothers will be randomized after the completion of

breastfeeding to continued TMP/SMX vs. discontinuation of TMP/SMX prophylaxis, and 100 HIV-uninfected

children born to HIV-uninfected mothers will not be given TMP/SMX prophylaxis

Inclusion criteria:

1. Age 6 weeks to 9 months

2. Documented HIV-1 status of mother and child

3. Agreement to come to the study clinic for any febrile episode or other illness

4. Agreement to avoid medications administered outside the study protocol

5. Guardian age 18 years or older (no age limit for parents)

6. Parent or guardian willing to provide informed consent

7. Residence within a 30 km radius of the study clinic

Exclusion criteria:

1. Intention to move more than 30 km from the study clinic during the follow-up period

2. History of allergy or sensitivity to AL or DP or TMP/SMX

3. Active medical problem requiring in-patient evaluation at the time of screening

4. HIV exposed children that have already stopped breast feeding and TMP/SMX prophylaxis

Follow-up:

Participants will be followed until they reach 21 months of age for all of their outpatient medical care in our

study clinic. Routine home visits will be done on any participant not seen in our study clinic after any

consecutive 30-day period. Patients presenting with a new episode of fever will undergo standard

evaluation for the diagnosis of malaria.

Malaria case definition

Uncomplicated malaria (all of the following):

1. Documented fever or history of fever in the prior 24 hours

2. Positive thick blood smear

3. Absence of complicated malaria

Complicated malaria (any of the following):

1. Evidence of severe disease with a positive thick blood smear

2. Danger signs with a positive thick blood smear

3. Parasite density > 500,000/ul

Activity Narrative:

Progress to date:

As mentioned above, enrolment started in July 07 after IRB approval was given in May 07. An MOU has

been signed between TDH, PREFA, CDC, MU-UCSF and TASO Tororo from which an important part of the

HIV positive children is expected to be recruited. Tororo authorities and TDH staff have been induced to the

study goals and objectives and given the study protocol for input. Clinical and data staff has been hired,

trained and has moved to Tororo. A designated study clinic has been established within TDH and is open

daily from 8:00 am to 5:00 pm 7 days a week while after-hours care is available at Tororo Hospital. Clinical,

molecular, and immunology studies are being conducted at affiliated laboratories at the CDC/UVRI research

center in Entebbe, the Joint Clinical Research Center in Mbale, MU-UCSF Molecular Laboratory in

Kampala, and the University of California, San Francisco.

Planned FY08 activities:

In FY08, we plan to have completed enrolment and to be able to focus on follow-up of the children. By mid-

08, we will be able to conduct an interim analysis on the general biological and socio-demographic

characteristics of the cohort, loss to follow-up, HIV transmission rates, malaria incidence and recurrence

rates, ACT and ARV drug adherence rates as well as child mortality. We will be also able to make

preliminary comparisons between the HIV-infected and non-infected groups.

Additional CDC contributions in kind:

•Home visitors (on loan from CDC/HBAC)

•Motorcycle maintenance

•Fuel for home visits

•CBCs for 400 infants (baseline + q3 months)

•CD4 counts/percents for 100 infants (baseline + q3 months)

•Viral loads for 50 children on ART (baseline + q3 mos)

•Administrative and logistics support (IT & data support - Lab HR, supervision, QC, sample transport and

storage - Office space)

Salaries/fringe benefits: $91,160

Equipment: $12,750

Supplies: $22,100

Travel: $0

Participant Incentives: $2,500

Laboratory testing: $0

Other: $16,490

Total: $145,000

Budget Justification:

Study costs mainly comprise of personnel to conduct and supervise the study as well as contingency funds

for drugs. A local area network will need to be set up independently of this operated by CDC as CDC safety

regulations do not authorize non USG personnel to have access to its network.

Incentives for participants include free clinical care for all malaria and non-malaria illnesses for all children

and mothers participating in the study as well as full reimbursement of transportation costs for all clinic

visits.

Both HIV-positive and HIV-negative mother-baby pairs receive a basic care package as part of the program.

PCR tests and CD4 counts are being done at CDC and JCRC labs and samples are transported by CDC

vehicles.

Infants are monitored at the clinic on a bi-monthly basis and during unscheduled visits when sick by a hired

clinical officer. Defaulters are visited at home by 2 field officers on motorcycle who have been made

available on loan from CDC Tororo staff. The study has hired 2 data clerks and one data manager to track,

collect, enter, clean and pool data.