The number of people in the world living with HIV has reached an estimated 42 million and is still growing with some 5 million new infections each year. An annual toll of 3 million deaths is rapidly increasing the ranks of the 20 million people who have already died of AIDS. In Africa, the most severely affected region, the estimated number of children orphaned by AIDS has exceeded 11 million and in the hardest hit countries more than one-third of young women are infected with the HIV virus.
Other sexually transmitted infections (STIs) also contribute to a widespread but largely unacknowledged epidemic with some 340 million new infections each year caused by microorganisms other than the HIV virus.
Because of the high prevalence of HIV and other STIs, and the seriousness of the diseases they cause, research to improve the efficiency and effectiveness of control measures is urgent. The difficulty and cost of treating STIs, and the fact that some STIs, especially HIV infections, are not curable, places a great premium on prevention.
Because the risk of STIs is so intimately conditioned by behavior, studies go beyond the search for disease prevention technology. They address relevant economic, social and cultural issues such as community level education and women’s equality and autonomy in making decisions about their sexual behavior.
The majority of new infections in developing countries are transmitted through heterosexual contact. A common pattern of transmission of HIV and other STIs in developing countries is from commercial sex workers to their male clients and in turn to their girlfriends and wives. Although the male latex condom is an effective way to prevent STI transmission, its use requires male cooperation. Many women in all settings, but especially in developing countries, are not in a position to successfully negotiate condom use. This has led to two of the major goals: to develop simple “woman-controlled” technologies that would allow women to protect themselves against STI transmission and research to better understand the cultural, educational, economic and gender related power correlates of high-risk behavior and to test intervention strategies that decrease the risk of contracting sexually transmitted diseases.
FACES is an HIV/AIDS care and treatment program in Western Kenya and Nairobi. FACES is a collaboration between the Kenya Medical Research Institute (KEMRI) and UCSF, funded through the US President’s Emergency Plan for AIDS Relief (PEPFAR). Formed in September 2004, FACES’ mission is to provide accessible comprehensive care and support services to HIV-affected families and other vulnerable populations in Kenya, reinforce prevention practices, and train Kenyan health workers in scientifically sound HIV/AIDS care. FACES also serves as a platform for an increasing number of operational research studies, which include the following:
- Integration of HIV Care and Treatment into Maternal and Child Health
A study is being carried out to determine the most effective way to reach and provide pregnant women with accessible, comprehensive, and high quality HIV care and treatment. Funded by CDC as a Public Health Evaluation, this study is taking place in Migori District, Kenya with implications for other sites in Kenya and sub-Saharan Africa. This study utilizes a prospective cluster randomized design. Twelve clinics similar in size, population, and services in Migori District, Kenya that provide antenatal care have been randomly assigned to either receive “integrated antenatal care, Prevention of Mother-to-Child Transmission & HIV services” (intervention arm) or “non-integrated services” (control arm).
- HIV/AIDS Stigma and Use of Services by Pregnant Women
Funded by the National Institute of Mental Health, a study is examining the effects of different types of HIV/AIDS stigma on use of maternity services and HIV services by pregnant women in Kenya. This is a prospective study among pregnant women using antenatal care clinics in Migori and Rongo Districts of Nyanza Province. It involves structured interviews using PDAs and collection of data from medical records, as well as qualitative in-depth interviews.
- Formative Research for Intervention of HIV/AIDS Service Providers on Gender-Based Violence
Preliminary data from pregnant women in rural Kenya indicate that fear of violence from a male partner is an important reason why some women refuse HIV testing, and that pregnant women who test HIV-positive or refuse testing may be more likely to be victims of violence. In response to these findings, an intervention on gender-based violence (GBV) for health workers who provide HIV-related services to pregnant women in this setting will be developed. In order to first gain in-depth contextual understanding of GBV, focus groups and in-depth interviews are being conducted with pregnant women, men, and a variety of service providers (health, law enforcement, education, women's groups, and village leadership) in rural Nyanza Province, Kenya. The knowledge gained through this formative research will be used to develop a GBV intervention for health workers, taking advantage of existing Kenyan GBV training programs. Subsequently, a preliminary pilot of the adapted intervention will be carried out to assess feasibility and acceptability. The results of this pilot study will form the basis for future research on a larger scale to examine the impact of addressing GBV on prevention of HIV/AIDS. This study is being funded through a Pilot Award from the UCSF Center for AIDS Research.
- Integration of Family Planning Services into HIV Care and Treatment
A study is being conducted to determine how to best meet the family planning needs of HIV-infected women in Kenya. Funded by the Tides and Gates Foundations, this study is a cluster-randomized trial comparing the effects of integrating family planning services into HIV care and treatment programs in Nyanza Province, Kenya, with the standard referral for family planning services outside of HIV care and treatment programs. The study is specifically looking at contraceptive uptake, contraceptive continuation, and unintended pregnancy rates.
- Fertility Desires and Family Planning among HIV-Infected Couples
A study is exploring decision-making and relationship power around fertility and family planning among HIV-affected couples and community leaders in Nyanza Province, Kenya. This is a qualitative, hypothesis-generating research project which involves in-depth, open-ended interviews with couples who present to HIV clinics for care, couples from high prevalence HIV communities, and individual community leaders. The study is funded by the Hellman Foundation and by the Center for AIDS Research at UCSF.
- Pre-Exposure Prophylaxis to Prevent HIV Acquisition within Discordant Couples
Novel strategies are needed to prevent HIV-transmission within HIV discordant couples. Addressing this issue, the UCSF-KEMRI site in Kisumu, Kenya is one of eight sites in a multi-site trial funded by the Gates Foundation and coordinated by the University of Washington. This study is a Phase III safety and efficacy trial that is examining the effects of taking once-daily pre-exposure prophylaxis (PrEP) on HIV acquisition within discordant couples. Pre-exposure prophylaxis involves HIV-1 uninfected individuals at high risk for contracting HIV-1 taking antiretroviral medications (PrEP) to maintain blood and genital drug levels to prevent HIV-1 acquisition. This study hypothesizes that PrEP will decrease HIV-1 acquisition among HIV-uninfected individuals within HIV discordant couples, if found to be safe and efficacious.
- Risk Reduction in HIV Discordant Couples Attempting Conception
HIV negative partners in discordant heterosexual relationships are recognized as a high-risk group for sexual transmission of HIV in sub-Saharan Africa. Efforts to reduce HIV transmission in this group do not address the concerns of couples who desire children. A study is being carried out in Kisumu, Kenya to develop a preliminary understanding of the social and cultural context in which these couples are making the decision to conceive, and to explore the hypothetical acceptability of risk reduction strategies for discordant couples attempting conception. Discordant couples of reproductive age who express a general desire to have children in the future are recruited to participate in a structured questionnaire followed by an in-depth interview. Findings will be used to design an investigation to determine the uptake and acceptability of interventions to reduce HIV transmission for HIV discordant couples attempting conception. This study has been funded through a UCSF Center for AIDS Prevention Studies (CAPS) Innovative Grant.
- Prevention of Tuberculosis in HIV-Infected Children
A study is being carried out in Kenya to evaluate the effectiveness of Isoniazid Preventive Therapy (IPT) in HIV-infected children to reduce TB incidence, morbidity and mortality. The hypothesis is that IPT will effectively reduce TB and overall morbidity and mortality in the study population. If this should occur, the Kenya National Leprosy and Tuberculosis Program can consider national guidelines for IPT in children. This study is funded through UCSF discretionary funds, including private donations.
- Effect of HAART on Surgically Treated HGCIN in HIV-infected Women
A study is being carried out to assess the effect of Highly Active Antiretroviral Therapy (HAART) on the recurrence of surgically treated High-Grade Cervical Intraephithelial Neoplasia (HGCIN) in HIV-infected women in Kenya. This is a prospective cohort study of HIV-infected women receiving care in the city of Kisumu. Women with HGCIN are being followed for two years after their initial surgical excision to determine the effect of HAART on the recurrence of HGCIN after surgical excision. The study is being funded through UCSF discretionary funds, including private donations.
- HIV and Dementia
The HIV Neurology in Kenya (THINK) Dementia Study is working to validate a diagnostic tool for use by non-physician health care providers to diagnose HIV-associated dementia. It is a cross-sectional study which involves validating the diagnostic tools against a structured history, neurological exam, neuropsychological testing and imaging with computed tomography. Subjects are being recruited from sites throughout Nyanza Province. This study is being funded by the American Academy of Neurology Foundation (AANF) and an NIH Fogarty International Clinical Research Fellowship (FICRF).
- Impact of Antiretroviral Therapy on Sexual Risk Behaviors
An ongoing study is examining the association of Antiretroviral Therapy (ART) expansion and ART-related beliefs with risky sexual behaviors, both in HIV-positive patients receiving HIV care and in the general population of Kisumu, Kenya. The goal of this research is to produce a community assessment to inform prevention programs. It also aims to establish a monitoring system to follow changing knowledge and beliefs and sexual risk behaviors as ART roll-out progresses. The initial research for this study was funded by the Doris Duke Foundation.
- Application of weighted time-series to address bias in evaluation of clinic and community-level research
A study is being conducted to develop, test, and apply new analytic methods to the evaluation of the effectiveness of community- and clinic-level interventions in Kenya. It is using a simulation to compare results using weighted time-series and conventional methods within the context of a clinic-level intervention. The results of this study will be used to seek funding to test the broader application of these methods in both community- and clinic-level interventions. Application of these methods has the potential to improve evaluation of many community-level interventions, particularly in settings where it is difficult to obtain individual-level information or to follow individuals in the community over time (e.g. rural or other hard to reach populations). The study is funded through UCSF Center for AIDS Prevention Studies (CAPS) Innovative Grants.
- International Epidemiologic Databases to Evaluate AIDS (IeDEA)
Funded by NIH through Indiana University, IeDEA is striving to build regional population-based HIV knowledge and information. IeDEA is pooling data from collaborating provider and research networks in East Africa to cost-effectively generate large data sets to address high priority research questions. UCSF’s Family AIDS Care and Education Services (FACES) contributes to IeDEA by sharing its HIV data. Data collection, merging, storage, and sharing across sites in the East African Region, focuses on:
- cost-effectiveness of HIV care, treatment, and prevention strategies;
- appropriate guidelines for initiation of first-line therapy for treatment of HIV/AIDS;
- genetic variability of HIV;
- issues related to first-line therapy failure;
- adherence to HIV treatment;
- contextual issues and resource limitations of HIV care delivery in resource-limited settings;
- impact of tuberculosis infection on HIV/AIDS care and treatment in the developing world;
- prevention of mother-to-child transmission of HIV
The NIH-funded CTU conducts multiple HIV/AIDS clinical research trials implemented at the University of Zimbabwe (UZ)-UCSF Collaborative Research Programme in Harare, Zimbabwe. The primary goal of the UZ-UCSF CTU is to carry out the clinical research plans of the DAIDS HIV/AIDS Networks specifically in the areas of a) microbicides for HIV prevention, b) non-vaccine HIV prevention strategies; c) clinical management of HIV/AIDS, including co-infections and other HIV-related conditions, and translational research for new drug development; and d) prevention of mother-to- child transmission and clinical management of HIV, including co-morbidities and other HIV-related conditions in children, adolescents and pregnant women. We are proud to be one of the 73 selected CTUs which collaborates with the networks’ leadership, the world’s leading researchers, and local domestic and international communities to conduct clinical trials addressing the highest priorities in HIV/AIDS research.
- Optimal Combined Therapy After Nevirapine Exposure (OCTANE) (A5208)
Consisting of two trials, A5208 is comparing the virologic response to NNRTI-based versus protease inhibitor (PI)-based anti-HIV therapy in HIV-infected women who only received a single dose of nevirapine at childbirth to prevent mother-to-child transmission (Trial 1), with those who have been on anti-HIV therapy prior to childbirth (Trial 2).
A Phase I/II Dose-Finding Study of High-Dose Fluconazole Treatment in AIDS-Associated Cryptococcal Meningitis (A5225)
This study will explore the safety, tolerability, and therapeutic of a new treatment regimen with high-dose fluconazole for management of cryptococcal meningitis in HIV-infected patients.
International Trial of Modified Directly Observed Therapy Versus Self-Administered Therapy for Participants with First Virologic Failure on a Non-Nucleoside Reverse Transcriptase Inhibitor-Containing Antiretroviral Regimen (A5234)
This study aims to determine if modified directly observing therapy (mDOT) will improve adherence and the ability to fight HIV infection among HIV infected participants whose first anti-HIV regimen did not work.
- Sensitivity and Specificity of Mycobacterium Tuberculosis Screening and Diagnostics in HIV-Infected Individuals (A5253)
An exploratory, observational, prospective, cross-sectional study designed to construct a standardized diagnostic evaluation (SDE) that improves the diagnosis of pulmonary TB as compared to standard of care (SOC) TB screening in HIV-infected persons not currently receiving ART.
- A Randomized Trial to Evaluate the Effectiveness of Antiretroviral Therapy Plus HIV Primary Care Versus HIV Primary Care Alone to Prevent the Sexual Transmission of HIV-1 in Serodiscordant Couples (HPTN 052)
This trial is trying to determine whether antiretroviral therapy can prevent the sexual transmission of HIV in couples where one partner is HIV-positive and the other is HIV-negative.
- Phase III Trial to Determine the Efficacy and Safety of an Extended Regimen of Nevirapine in Infants Born to HIV Infected Women to Prevent Vertical HIV Transmission During Breastfeeding (HPTN/IMPAACT 046)
This study is evaluating the efficacy and safety of an extended regimen of nevirapine in infants from 6 weeks to 6 months, or through the end of breastfeeding, whichever is earliest, for preventing mother-to-child transmission of HIV through breast milk, in comparison with infants taking placebo after taking nevirapine for the first 6 weeks of life.
- Integrating Family Planning into PMTCT: A Novel Approach in Zimbabwe (IMPAACT/HPTN 046 PEPFAR)
This study aims to test the feasibility of implementing an intervention to integrate family planning into antenatal care (ANC) and PMTCT services for HIV-infected Zimbabwean women.
- Phase II, Parallel, Randomized, Clinical Trials Comparing the Responses to Initiation of NNRTI-Based Versus PI-Based Antiretroviral Therapy in HIV Infected Infants Who Have and Have Not Previously Received Single Dose Nevirapine for Prevention of Mother-to-Child HIV Transmission (P1060)
This study is comparing the effectiveness of a non-nucleoside reverse transcriptase inhibitor-based regimen versus a protease inhibitor-based regimen in HIV-infected infants who have or have not been exposed to nevirapine.
- Dose Finding and Pharmacogenetic Study of Efavirenz in HIV-Infected and HIV/TB Co-Infected Infants and Children ≥ 3 Months to <36 Months of Age (P1070)
This study is investigating the pharmacokinetics and safety of efavirenz capsules in HIV-infected infants and children ≥ 3 months to <36 months of age who live in low and middle income countries with a high incidence of tuberculosis. This will then help determine the best dosage of efavirenz in children who are less than three years of age.
- Safety and Immunogenicity of Rotavirus Vaccine (P1072)
This study aims to evaluate the safety and immunogenicity of the Rotavirus vaccine candidate, RotaTeg, in HIV-infected and uninfected children born to HIV-infected mothers.
- Pilot Study of Immune Reconstitution Inflammatory Syndrome (IRIS) for International Sites Participating in IMPAACT Protocols Involving HAART Initiation in Infants and Children (P1073)
This study aims to determine if starting HAART is related to a special set of symptoms called IRIS. IRIS is sometimes caused by TB or the vaccination that prevents TB.
- Promotion of Maternal Infant Survival Everywhere (PROMISE) (P1077)
PROMISE is a research protocol designed to address in an integrated and comprehensive fashion four critical questions currently facing HIV-infected pregnant and postpartum women and their infants: 1) What is the optimal intervention for the prevention of antepartum and intrapartum transmission of HIV; 2) What is the optimal intervention for the prevention of postpartum transmission in breast feeding (BF) infants; 3) What is the optimal intervention for the preservation of maternal health after the risk of period for MTCT ends (either at delivery or at cessation of BF); 4)What is the optimal intervention for the prevention of the infant morbidity and mortality associated with BF cessation.
- A Phase IIB Safety and Effectiveness Study of Tenofovir 1% Gel, Tenofovir Disoproxil Fumarate (TDF) Tablet and Tenofovir DF-Emtricitabine Tablet for the Prevention of HIV Infection in Women (VOICE) (MTN 003)
This study is looking at the safety and effectiveness of daily tenofovir gel in comparison to vaginal placebo gel, and the safety and effectiveness of oral tenofovir disoproxil fumerate and oral tenofovir disoproxil fumerate/emtracitabine tablet compared to oral placebo in preventing HIV infection among women at risk for sexually transmitted infections.
- Bone Mineral Density Substudy to MTN 003 (VOICE) (MTN 003B)
This sub-study of MTN 003 is trying to determine if the oral study medications in MTN 003 have an effect on bone mineral density.
- An Observational Cohort Study of Women Who Became Infected with HIV During Their Participation in MTN Trials That Aims to Understand How Microbicides or Oral Prevention May Affect the Natural History and Progression of HIV (MTN 015)
This study is observing women who become HIV-infected during their participation in a microbicide trial, and is specifically trying to determine how microbicides or oral prevention medications may affect the natural history and progression of HIV.
- Evaluation of Maternal and Baby Outcome Registry After Chemoprophylactic Exposure (EMPBRACE) (MTN 016)
This study is observing women who become pregnant during their participation in a microbicide trial, and is specifically looking at the prevalence of spontaneous pregnancy loss or major malformations in infants with mothers exposed to an active study agent during pregnancy in comparison to those mothers not exposed to an active study agent during pregnancy.