Given the synergistic epidemics of HIV and TB in southern Africa, the question of how and when to integrate HIV and TB treatment in co-infected patients is a critical one. Here at the Conference on Retroviruses and Opportunistic Infections, Drs. Diane Havlir and Salim Abdool Karim presented important results from two randomized clinical trials attempting to answer this question.
Havlir presented the results from ACTG 5221 or the STRIDE study that enrolled 806 patients from four continents in a study comparing the impact of initiating antiretroviral therapy (ART) within two weeks of beginning TB therapy, with initiating ART eight to 12 weeks after the commencement of TB therapy. The end points of the study were all causes of mortality and AIDS-defining illnesses. The median time for initiation of therapy in the so-called immediate arm was 10 days and in the “early” arm it was 70 days.
Abdool Karim presented results from the two remaining arms of the SAPIT study, which had already determined that delaying ART until after the completion of TB treatment dramatically increased mortality. The other two arms randomized 642 patients to receive ART during the first four weeks of TB treatment or at the end of the intensive phase of TB treatment after several months. The end points of the study were the same – mortality or progression to AIDS.
The bottom line in both studies was that earlier ART significantly reduced mortality and disease progression in persons with late stage AIDS – those with CD4 counts less than 50. However there were no significant differences in mortality or progression to AIDS for those with higher CD4 counts between those in the earlier treatment arms and those who received ART later in the course of their TB treatment. In both studies, those who received ART earlier were more likely to experience immune reconstitution inflammatory syndrome or IRIS.
Following up on the two presentations, Myron Cohen, MD, from the University of North Carolina and member of the Scientific Advisory Committee of the Center for Global Health Policy, raised a question and concern about the World Health Organization guidelines that currently state, “ART should be initiated for all people living with HIV with active TB disease irrespective of CD4 cell count. TB treatment should be started first, followed by ART as soon as possible and within the first 8 weeks of starting TB treatment.”