HIV AND TB TREATMENT RESEARCH
is headed by Kogie Naidoo in association with Nesri Padayatchi.
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.