The HIV/AIDS pandemic remains among the investigators greatest public health challenges. In the absence of an effective vaccine, focus has shifted to other prevention strategies such as pre-exposure prophylaxis. Tenofovir, with potent activity against retroviruses [1], was developed for oral use as Viread®, which is widely used for HIV treatment. The efficacy of Viread® has been demonstrated in treatment-experienced and naïve patients [2,3]. In antiretroviral-naive patients, the combination of tenofovir with lamivudine and efavirenz has been classified as a preferred regimen in the Department of Health and Human Services treatment guidelines[4], and has been adopted by the South African Department of health as the first line regimen in treatment-naïve HIV infected patients since April 2010. The durability of antiviral response, favourable resistance profile, once daily dosing, and excellent long term safety profile of tenofovir [5], makes this drug an attractive option in both treatment and prevention regimens and its long half-life [6], made it an ideal choice as the first antiretroviral drug to be formulated as a microbicide gel. The CAPRISA 004 study conducted in South Africa which tested the effectiveness and safety of 1% tenofovir gel showed that the use of tenofovir in a gel formulation reduced HIV acquisition by 39% overall, and by 54% in women with high gel adherence [7]. There have been concerns raised regarding the use of tenofovir in both PrEP and treatment regimens due to the potential for selection of viral mutations and development of resistance in patients who have become HIV-infected while on PrEP. There have been no studies conducted to determine whether using tenofovir in pre-exposure prophylaxis affects treatment outcomes in patients who later use tenofovir, which is part of the first line ART of South Africa. This study aims to determine whether prophylactic exposure to tenofovir gel alters the therapeutic response to a tenofovir containing antiretroviral regimen.
Name: Tenofovir, lamivudine and efavirenz
Description: Tenofovir, 300mg daily, lifelong Lamivudine, 300mg daily, lifelong Efavirenz, 600mg daily, lifelongType: DrugTenofovir, lamivudine and efavirenz Zidovudine, lamivudine and efavirenz
Description: Treatment failure is defined as viral load > 50 copies/ml, antiretroviral regimen changes for treatment failure or death
Measure: The Antiretroviral Treatment Failure Rate at 12 Months. Time: 12 months post ART intiation or until time of deathDescription: Difference between 12 months and randomisation CD4+ count was calculated and then summarised
Measure: Change in CD4+ Cell Count From Randomisation to 12 Months Post-randomisation Time: Measured at 12 months post ART initiationDescription: We will assess whether exposure to tenofovir gel at the time of HIV acquisition alters the subsequent humoral and cellular immune responses following antiretroviral treatment initiation
Measure: Cellular and Humoral Immune Responses Time: 3 yearsAllocation: Randomized
Parallel Assignment
There are 2 SNPs
Tenofovir Resistance, Defined as Presence of K65R, K70E or Any of the TAMS Mutations. --- K65R ---
Treatment failure is defined as viral load > 50 copies/ml, antiretroviral regimen changes for treatment failure or death Secondary Endpoints: 1. Change in CD4+ cell count from the earliest post-infection timepoint to the time of randomisation to 12, 24 and 36 months post-randomisation 2. Tenofovir resistance, defined as presence of K65R, K70E or any of the TAMS mutations. --- K65R ---
Tenofovir Resistance, Defined as Presence of K65R, K70E or Any of the TAMS Mutations. --- K65R --- --- K70E ---
Treatment failure is defined as viral load > 50 copies/ml, antiretroviral regimen changes for treatment failure or death Secondary Endpoints: 1. Change in CD4+ cell count from the earliest post-infection timepoint to the time of randomisation to 12, 24 and 36 months post-randomisation 2. Tenofovir resistance, defined as presence of K65R, K70E or any of the TAMS mutations. --- K65R --- --- K70E ---