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UCSF is one site of an NIMH-funded multi-site, international efficacy trial of a behavioral intervention to reduce the incidence of HIV infection. Collaborating international sites teamed with US sites are: Zimbabwe (S. Morin, UCSF PI), South Africa (T. Coates, UCLA PI), Tanzania (M. Sweat, Johns Hopkins University PI) and Thailand (D. Celantano, Johns Hopkins University PI). In this prevention trial, 34 communities in Africa (Tanzania, Zimbabwe, and South Africa) and 14 communities in Thailand will be randomized to either a community-based HIV voluntary counseling and testing (CBVCT) intervention or clinic-based standard VCT (SVCT). The intervention has three major strategies:

1. To make VCT more available in community settings
2. To engage the community through outreach and community mobilization
3. To provide post-test support services

These strategies are designed to change community norms and reduce risk for HIV among all community members, irrespective of whether they participated directly in the intervention. Thus, we plan a community-level sampling approach as opposed to a cohort design to evaluate outcomes.

The overarching goal of this program project (P01) is to evaluate novel and strategic interventions to reduce the burden of malaria and improve HIV outcomes among children and pregnant women, the populations most affected by the overlap of these diseases. We hypothesize that treatment with HIV protease inhibitors (PIs) will lower the incidence of malaria and consequent morbidity in HIV+ children and pregnant women compared to those treated with standard antiretroviral treatment. This hypothesis is based on the appreciation that malaria parasites and HIV express biochemically similar proteases and the observation that HIV PIs exert potent in vitro antimalarial activity. We hypothesize that in HIV- children, chemopreventive therapy will offer strong protection against malaria without increased malarial morbidity after discontinuation of the intervention. We hypothesize that intermittent or chronic antimalarial and PI-based antiretroviral therapy will select for drug resistant parasites, and that different drugs will offer different selective pressures. Four interlinked studies to test these three hypotheses comprise our P01 projects:

1. Protease inhibitors for the prevention of malaria in HIV-infected children
2. Protease inhibitors to reduce malaria morbidity in HIV-infected pregnant women
3. Chemopreventive therapy for malaria in HIV-uninfected infants and children
4. Selection of drug resistant malaria parasites by antimalarial and HIV therapies

The projects will enroll a total of 1600 participants and be implemented by a multidisciplinary, multinational team in Tororo, Uganda, a site of high malaria transmission. The Administrative and Data and Statistics Cores will support the four projects. CAPS will spearhead the Data and Statistics Core for this P01.

The HIV and malaria epidemics inflict the greatest harm in sub-Saharan Africa and overlap significantly. We have recently identified an interaction between acute malaria and false positive HIV EIA test results. This project will investigate this interaction in three of the most common rapid EIA HIV tests used in sub-Saharan Africa among a cohort of 450 HIV-uninfected children aged 2-17 years being followed longitudinally for malaria in Kampala, Uganda as part of a larger, parent study. Children will be HIV counseled and tested once at baseline. For those who test HIV-negative we will retest blood samples at the time of first new malaria diagnosis using samples already being collected for the parent study, and again as blood is collected for the parent study for a period of up to 180 days. The study will be conducted at the MU/UCSF Malaria Clinic in Kampala, Uganda. The study clinic is located within the Mulago Hospital Complex, the primary referral hospital in Uganda. The aims of the study are to:

• Determine the prevalence of false positive HIV EIA test results in children with uncomplicated malaria.
• Estimate the duration of false positive HIV EIA test results in children with uncomplicated malaria.
• Compare the positive predictive value, sensitivity and specificity of serial rapid HIV testing algorithms to parallel rapid HIV testing algorithms in children with uncomplicated malaria.
• Identify risk factors and predictors of false positive HIV EIA test results in children with malaria.

Three recent independent national datasets suggest that the rate of new HIV infections in Botswana appears to be declining, as evidenced by decreased prevalence among pregnant women aged 15-49. However, it is still uncertain why these declines have been observed and the extent to which behavioral changes (e.g., monogamy, condom use) have been causally associated with the decline. The goal of this study is to use qualitative research methods to lend additional depth to existing surveillance data that suggest that HIV prevalence among young people in Botswana is declining. Focus group discussions and individual in-depth interviews are conducted with

• Local youth service providers
• Youth between the ages of 18-24
• Adult key informants in three districts selected for regional diversity and variation of trends in HIV prevalence

By gathering information from young people and key informants who provide health-related services to young Batswana, we will gain valuable insight into the behavioral and contextual factors that may assist in explaining the observed decreases in HIV prevalence. Qualitative methods will allow us to explore the meanings and variations of the sexual experiences of young Batswana. This work may also lead to the development of innovative behavior change strategies to help support the decreased spread of HIV in Botswana.

South Africa is the country most impacted by HIV in the world—of 49 million people, 5.6 million are infected with HIV. In 2011 the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) and Centers for Disease Control and Prevention (CDC) responded to the epidemic crisis by stepping up prevention partnerships across South Africa through support for comprehensive HIV/TB prevention programs. The International Training and Education Center for Health in South Africa (I-TECH) was awarded funds to partner with the North West Province Department of Health (NWDOH), Empowerment Concepts, the University of California San Francisco’s Center for AIDS Prevention Studies, LifeLine and Soul City to develop, implement, and evaluate a comprehensive HIV prevention program in the province. Comprehensive prevention packages incorporate biomedical, behavioral and structural interventions, recognizing there is no silver bullet to prevent HIV but “that the optimal set of interventions implemented with quality and to scale can significantly reduce HIV incidence.” UCSF has supported this work by conducting a situational analysis, to tailor the programming to the local context; providing technical assistance in programming components; creating an infrastructure for community engagement through community working groups; supporting quality assurance, monitoring and evaluation; and leading an impact assessment of the project.