Study Period: 2002 to 2008
Source of Funding / Funder: NIH/NIAID

Project Details:

This study involved 146 HIV-positive individuals recruited at JCRC. This randomized trial evaluated the effects of continuous vs 2 approaches to short cycle intermittent ART on viral load. We evaluated both the 7 days on-HAART/ 7 days off-HAART as well as a 2 days off­ HAART/ 5 days on-HAART approach.

Secondary study objectives included changes in CD4 T-cell count, virus resistance patterns, toxicity and side effects, quality of life and adherence. Interrupted therapy was expected to minimize toxicity/ side effects and reduce costs.

In the study, structured treatment interruptions of 5 days on and 2 days off treatment were found to be equivalent in outcomes to continuous treatment. The results of this study inspired the development of the PENTA 16 (BREATHER) trial in adolescents, where JCRC is the only African centre, as described below.

The project also has stored samples that may be used to answer additional questions. Scholars may benefit from these ready to use samples.

Project Details:

This SARA protocol separately explored issues of the best specific regimens for second-line combination ART following first-line 2NRTI/NNRTI or triple NRTI regimens, specifically, which ARV combinations could best provide an optimised background regimen to support Aluvia.

It was a three centre open-label randomised trial in HIV infected adults receiving Aluvia containing second-line ART in Africa to evaluate the efficacy of maintenance monotherapy with ritonavir-boosted lopinavir (Aluvia tablets) following initiation with 24 weeks of combination therapy in second-line ART in Africa.

The main objective was to compare two strategies for second-line ART after 24 weeks of combination Aluvia (or Kaletra) containing ART: Arm 1: continued combination Aluvia-containing ART; Arm 2: maintenance with Aluvia monotherapy. Patients were randomized in a 1:1 ratio and followed up to 96 weeks. The initial data were encouraging and this was the basis for a larger clinical end-point trial called EARNEST (described below).

Study Period: 2003 to 2009
Source of Funding / Funder: MRC, DFID, Rockefeller Foundation

Project Details:

DART, the largest ART clinical trial in Africa was an open randomized trial evaluating strategic approaches for the management of ART in previously untreated symptomatic HIV infected adults with CD4 cell counts <200 cells/mm³ initiating ART in Africa. A total of 3316 HIV infected symptomatic ART naïve adults took part across three centres in Uganda, and one in Zimbabwe. The main question was whether clinical monitoring only would be as safe and effective as clinical and laboratory monitoring for toxicity (haematology and biochemistry) and efficacy (CD4 counts); no virological monitoring was performed.

A second part, comparing structured treatment interruptions (STIs: 12 weeks on, 12 weeks off ART) with continuous ART in patients who achieve CD4 cell counts ≥300 cells/mm³ after 48 or 72 weeks of ART was discontinued in March 2006 following DSMC review, and all patients were switched to continuous ART. The majority of patients were started on triple NRTI: 2469 patients initiated CBV/TDF, 300 CBV/ABC and 547 CBV/NVP. Minimum follow up of each patient was be 6 years.

It demonstrated that first-line ART can be delivered safely without routine biochemistry and haematology monitoring for toxic effects.

Participants from DART form a cohort for long term follow and a resource for answering pertinent questions to issues like long term efficacy, toxicities, resistance profiles and adherence issues.