Centre for the AIDS Programme of Research in South Africa
CAPRISA is a not for profit research organization that was established in 2002 through a consortium of five key institutions: University of KwaZulu- Natal, Columbia University, University of Cape Town, University of the Western Cape, and the National Institute for Communicable Diseases. The CAPRISA headquarters are located in the Doris Duke Medical Research Institute Research Institute at the Nelson R Mandela School of Medicine, University of KwaZulu-Natal.
Fellowship Site: Durban, South Africa; US Partner: Columbia University
DetailsInternational Site: Country:South Africa US Institution: US Director: Site Director: 2009 US Scholars: 2009 International Scholar: Log in to read the Site Handbook! |
The main goal of CAPRISA is to undertake globally relevant and locally responsive research that contributes to:
- Understanding HIV pathogenesis, prevention and epidemiology
- Interaction between Tuberculosis and AIDS
- Reducing mother to child transmission of HIV
Research Opportunities:
In keeping with this goal, CAPRISA contributes to research in five main areas: HIV Pathogenesis and Vaccines, HIV and TB treatment, Microbicides, Prevention and Epidemiology, and PMTCT.
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1. Prevention and Epidemiology
This research programme, based in Vulindlela, has revealed that HIV prevalence in pregnant women in this rural community has not changed substantially from 32.4% (95%CI 27.6-37.6) in 2001 to 34.4% (95% CI 29.4-39.2) in 2007 because high HIV-related mortality offsets the high incidence rates, estimated at 8.5% (CI: 4.0-12.9%) per annum in young women under the age of 30 years. Most of the prenatal clinic attendees were younger than 25 years of age; with 56.9% in this age range in 2001, and 63.2% in 2007. In 2007, the age specific prevalence was 36.4% among 20-24 year old women.
The toll of the HIV epidemic on young women makes the need for interventions to protect them from HIV infection imperative. Such interventions need to address risk factors for HIV infection, while simultaneously addressing the social, political, and economic factors that generate vulnerability and perpetuate risk. CAPRISA’s epidemiological studies have enhanced our understanding of the evolving HIV epidemic in South Africa by generating valuable information on HIV acquisition in young women to guide the development of interventions focused on your women.
The pivotal study in this programme is the CAPRISA 005 RHIVA (Reducing HIV in Adolescents) trial, a cluster-randomised controlled trial to assess the impact of a school-based intervention of incentivised behaviour change on HIV incidence in grade 9 and 10 children in 12 Vulindlela schools.
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2. Microbicides Research
The highest burden of HIV infection is in women younger than 30 years, making prevention interventions targeting adolescents and young women a high priority. Various sexual coupling patterns place young women at high risk, including partnering with older men who are more likely to be infected, multiple concurrent relationships, low marriage rates, low condom use rates, and limited skills in negotiating safer sex practices. Gender-based violence increases vulnerability, and poverty increases reliance on transactional sex for survival. Women are often unable to convince their male partners, especially husbands and regular partners, to use condoms. Notwithstanding the greater vulnerability of women, current options to reduce acquisition of HIV infection remain limited for women. New technologies to prevent the sexual transmission of HIV in women are urgently needed. Even a partially effective microbicide could have a profound impact on the dynamics of HIV transmission. According to mathematical modelling, 2.5 million HIV infections could be averted over 3 years if a microbicide with 60% effectiveness was used in 73 low-income countries. Hence, CAPRISA is conducting research aimed at discovering a safe and effective microbicide.
The pivotal study in the CAPRISA Microbicide Research programme is the CAPRISA 004 Tenofovir Gel Trial, which is a phase IIb, two-arm, double-blind, randomized, controlled trial assessing the safety and effectiveness of 1% tenofovir gel, in 900 HIV-negative, sexually active women between the ages of 18 to 40 years. Tenofovir is an antiretroviral agent, used widely in the treatment of AIDS. It has great potential as a microbicide gel because of its known safety profile in long term users and its long half life. Participants are followed up monthly. The trial includes multiple novel components including a theory based Adherence Support Program, and multiple mechanisms for measuring product use including laboratory markers. Accrual will be completed by the end of 2008 and follow-up will continue into the third quarter of 2009. In addition to a number of ancillary studies underway and planned linked to the trial the trial has a number of innovative facets including amongst others - a theory based customized adherence programme linked to biological and self-report measures of adherence and an enhanced informed consent process. The trial is being conducted at two clinical research sites, Durban and Vulindlela, located in KwaZulu-Natal, South Africa. The first and last participants were enrolled on 23 May 2007 and 15 January 2009 respectively, and results are expected in mid-2010.
The CAPRISA 004 Tenofovir Gel Trial presents a unique opportunity to conduct a range of ancillary clinical and laboratory studies on topical tenofovir to further advance the microbicide field. The TRAPS Program (Tenofovir gel Research for Advancing Prevention Science) has been established to address the following questions: 1) Does tenofovir abort HIV infection and initiate potentially protective host immunity?, 2) What tenofovir drug level correlates with protection against HIV and resistance? and 3) How does tenofovir alter natural HIV infection (including set point)? The CAPRISA 104 study, also an ancillary study in CAPRISA 004, is a case-control study to assess gel adherence in trial seroconvertors.
CAPRISA participates in several international microbicide activities including the Microbicide Trials Network, Quick Working Group and the Microbicide Development Strategy. New microbicide formulations are also being assessed for future studies.
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3. HIV pathogenesis and Vaccines
HIV pathogenesis and Vaccine research is headed by Koleka Mlisana.
The goals of HIV vaccines are to prevent infection and/or to slow the progression of HIV infection to clinical AIDS. Two of the key challenges in vaccine development are lack of clarity on what immune responses are needed and which components of the virus need to be targeted to protect against HIV infection. In an attempt to address these challenges, CAPRISA has been focusing since inception, on the earliest transmitted viruses and the earliest immune responses in acute HIV infection.
The pivotal study in this research programme is the CAPRISA 002 Acute Infection study which aims to characterize viral set point and clinical progression in subtype C infection and identify host, immunology and viral factors that predict disease progression.
The CAPRISA 002 Acute Infection study has shown that 1) there is a rapid loss of about half of the pre-infection CD4+ T cells during acute subtype C HIV-1 infection, 2) High proportion (~25%) of participants have rapid disease progression, needing antiretroviral therapy in the first 12 months of infection, 3) the severity of clinical signs and symptoms during acute HIV-1 infection are correlated with enrolment viral load but not with subsequent disease progression, 4) Diversity of virus at transmission impacts on disease progression, 5) Magnitude and breadth of HIV-1 specific CD8+ T cell gamma interferon Elispot responses at 3 months post-infection does not correlate with set point viral load, 6) Individuals with low set point viral loads have more early differentiated CD8+ T cells, 7) women with acute HIV infection had significantly elevated levels of inflammatory cytokines in their genital tract and plasma specimens, compared with HIV-negative control women, 8) Transmission of CTL escape variants provides HLA mismatched individuals with a survival advantage, 9) HLA-B*5801 is not associated with lower viral loads in the first year of infection, 10) The C3-V4 region is a major target of autologous neutralizing antibodies in HIV-1 subtype C infection, 11) Analysis of neutralization escape suggests limited neutralizing antibody specificities in early HIV-1 subtype C infection, 12) Early neutralization breadth in an HIV-1 subtype C infected individual is conferred by antibodies targeting the V1/V2 region, 13) Broad HIV-1 neutralization is mediated by plasma antibodies against the gp41 membrane proximal external region, 14) Approximately 80% of acute HIV infections involve a single virus (genetic bottleneck) in subtype C acute infection, 15) Reduced expression of TRIM5a is associated with higher likelihood of HIV-1 infection, 16) APOBEC3G mRNA levels were lower in peripheral blood mononuclear cells from HIV-1 –infected compared to HIV-1 uninfected subjects, 17) Chemokine copy number variations (CNV) on chromosome 17q12 can be an important determinant of HIV susceptibility.
CAPRISA is also involved in other collaborative studies in acute HIV infection; including a collaboration with the Center for HIV AIDS Vaccine Immunology (CHAVI) on the CHAVI 001 Acute Infection study and a collaboration with the University of Washington on potential mechanism of resistance to infection in highly exposed seronegative (HEPS) women.
CAPRISA participates in the NIH-funded HIV Vaccine Trial Network (HVTN) and is one of the sites conducting the HVTN 503 trial, a multicenter double-blind randomized placebo-controlled Phase IIB test-of-concept trial to evaluate the safety and efficacy of a 3-dose regimen of the Clade B-based Merck Adenovirus serotype 5 HIV-1 gag/pol/nef vaccine in HIV-1-uninfected adults in South Africa. This is one of the 2 Merck vaccine trials that have recently been prematurely terminated; CAPRISA is currently continuing with participant follow-up but enrolments and vaccinations have been discontinued. In preparation of future vaccine trials in adolescents, CAPRISA is one of the sites participating in the South African Studies on HIV in Adolescents (SASHA), led by University of Cape Town researchers.
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4. HIV and TB treatment Research
The integration of HIV and TB treatment is complicated due to concerns of drug interactions, pill burden, additive drug toxicities, immune reconstitution inflammatory syndrome (IRIS) and the potential negative impact on TB treatment services. Furthermore the high mortality associated with HIV-TB co-infection is a major challenge facing AIDS programs with no clinical trial data to guide timing of ART initiation in TB patients. Evidence is urgently needed for better treatment approaches to improve outcomes in HIV and TB co-infection.
The pivotal study in the CAPRISA HIV and TB Research programme is the CAPRISA 003 SAPiT ( Starting Antiretroviral therapy at 3 Points in TB) trial. This study is a three-armed randomized, open-label clinical trial that aims to determine the optimal time to start ART in patients on TB treatment by comparing clinical status as measured by CD4 count, viral load, mortality rates and opportunistic infections at 18 months in HIV/TB co-infected patients who initiated ART with TB treatment (early integrated treatment arm), at the end of the intensive phase of TB treatment (late integrated treatment arm) or upon completion of TB treatment (sequential treatment arm). Following a review of the data in September 2008, the independent Data Safety and Monitoring Committee recommended that all participants in the sequential arm be initiated on ART immediately as the mortality rate was 56% lower in the combined integrated treatment arms.
CAPRISA is also conducting two other HIV and TB treatment trials; the CAPRISA 001 START (Starting TB and Antiretroviral Therapy) trial and the AACTG network study A5221. The START trial, which completed follow-up in 2008, is a randomized, open-label controlled clinical trial to study the rifampicin – efavirenz interaction in 58 patients randomized to receive AIDS treatment either in conjunction with TB treatment (integrated arm) or upon completion of TB treatment (sequential arm). CAPRISA has enrolled 40 participants in the multi-centre A5221 trial that aims to compare the proportion of participants in the immediate ART arm versus the deferred ART arm surviving without AIDS progression.
A new pivotal study, the CAPRISA 005 TRuTH (TB Recurrence upon Treatment with HAART) study, which opens enrolment in 2009, will assess whether TB recurrence in treated TB-HIV co-infected patients is due to reactivation or reinfection. Inthis prospective cohort study, the mycobacterial strain from new episodes of TB in ex-SAPIT and ex-START trial participants will be compared to baseline stored mycobacterial to assess whether the recurrent TB episode is due to reactivation or reinfection. Innate and T-cell immunity will be assessed to identify potential immunological grounds which predispose to reactivation and reinfection.
A host of behavioural, operational and epidemiological studies are being conducted to address challenges in TB and HIV treatment. The CAPRISA 058: Enhanced Adherence Support Programme trial compares the effectiveness of two different adherence support strategies in patients with HIV-related TB, while CAPRISA 062 assesses if field-based directly observed therapy improves outcomes in TB and HIV co-infection. The CAPRISA 060 assesses the impact of antiretroviral therapy initiation on patient disclosure of HIV status, subsequent stigma/discrimation and treatment adherence. The CAPRISA 061 study measures HIV prevalence in TB patients to identify missed opportunities for integration of AIDS treatment into TB care.
The CAPRISA AIDS Treatment programme has, since its inception in 2004, provided a critically important health care service in Vulindlela and Durban by providing a comprehensive package of care, treatment and prevention. It is not specifically a research project but remains critically important for CAPRISA’s research.
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5. PMTCT Research
The pMTCT research is undertaken by at the Umlazi site of the University of KwaZulu-Natal’s Women’s Health Research Unit. This Unit is a partner site within the UKZN-CAPRISA Clinical Trials Unit. The Umlazi Site, which is situated in the Prince Mshiyeni Memorial Hospital in Umlazi Township about 17km southwest of the Durban city center, conducts research aimed at reducing the risk of HIV transmission from mother to child especially through breastfeeding, provides opportunities to address a critical remaining challenge in reducing mother-to-child transmission and also opportunities to study drug resistance patterns and its implications for subsequent pregnancies as well as implications for infant and maternal treatment drug choices and therapeutic effectiveness.
More than 40% of prenatal clinic attenders in Umlazi are HIV positive. An estimated 12,000 pregnancies and deliveries are managed each year at this facility, with an HIV prevalence of 42%. The current mother-to-child transmission (MTCT) rate is 6% at birth, 15% at 6 weeks and 20% at 9 months.
Housing/Meals/Transportation:
US trainees are provided with a car service on arrival for their transfer to their accommodation. Temporary housing at a Bed and Breakfast secured for their first month at CAPRISA and administrative support is provided to students to assist them in securing permanent housing for the rest of their traineeship period. Their orientation package includes a list of contact numbers, websites, and housing is preferably sought within a 1-10km distance from the CAPRISA offices to facilitate travel. Transportation is arranged for the first day of work, after which fellows are advised on safe and convenient public bus and taxi transport routes, shuttle services, and information for those interested in purchasing motor vehicles. The monthly stipend is generous in meeting housing, transport and living costs for the duration of the traineeship at above average living standards.
Generally the housing available for trainees consists either of an apartment or accommodation attached to a private residence or a cottage on a private residential property. The distance to the research facility would be dependent on where the accommodation is and trainees can either purchase a used car (and often take over the car from a trainee who has completed his fellowship) or alternatively, use a public bus service. Private taxis are also a reliable option but are more costly. Trainees often share the use of a car and running costs.
Health Issues:
The NIH/FICRS program requires all trainees to see a physician before they leave for assignment abroad. Please visit U.S. Centers for Disease Control and Prevention and The Yellow Book: Health Information for International Travel for more information.
Safety Issues:
Please visit the State Department website for more information.
Language requirements other than English:
The University of KwaZulu-Natal is an English speaking institution, therefore, English proficiency would ensure the ability of the foreign trainees to function effectively. The majority of the research participants in CAPRISA trials and patients in CAPRISA projects speak isiZulu. For more direct interaction with participants and patients it is desirable, but not essential, to have a working knowledge of isiZulu. In addition to private tutors, the university has special isiZulu language classes for medical students
What is it like to live in South Africa?
South Africa is an exhilarating and complex country. With its post-apartheid identity still in the process of definition, there is undoubtedly an abundance of energy and a sense of progress about the place. The climate is kind and there are few better places to see Africa's wildlife. Diversity is a key feature of South Africa, where 11 languages are recognised as official, where community leaders include rabbis and chieftains, rugby players and returned exiles, where traditional healers ply their trade around the corner from stockbrokers and where housing ranges from mud huts to palatial homes with swimming pools.Durban has a sub-tropical climate, getting very hot and humid in the summer months (November to February). The rest of the year has an extremely pleasant temperature and it never really gets cold. Durban lies in a summer rainfall area and is a popular summer holiday destination for South Africans because of its beautiful beaches. Durban also provides easy access to several game parks and the Drakensberg mountain range. In addition, it is about two hours drive away from the St Lucia wetlands, a world heritage site. The city has many good restaurants, theatres, shopping centres, movie houses and many other facilities to keep visitors entertained.
