Journal Article

Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda

Kaleebu, Pontiano, Hladik, Wolfgang, Asio, Juliet, Ruberantwari, Anthony, Kapaata, Anne A., Namuwenge, Norah, Downing, Robert, Katongole-Mbidde, Edward, Hughes, Peter, Lutalo, Tom, Watera, Christine, Parry, Chris M., Nannyonjo, Maria, Nazziwa, Jamirah, Nanyonga, Faith, Kirungi, Wilford, Lyagoba, Fred, Musinguzi, Joshua, Magambo, Brian

2015

Overview

With the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR). We implemented a WHO HIVDR prospective survey protocol at three treatment centers between 2012 and 2013. Data were abstracted from patient records at ART start (T1) and after 12 months (T2). Genotyping was performed in the HIV pol region at the two time points. Of the 425 patients enrolled, at T2, 20 (4.7%) had died, 66 (15.5%) were lost to follow-up, 313 (73.6%) were still on first-line, 8 (1.9%) had switched to second-line, 17 (4.0%) had transferred out and 1 (0.2%) had stopped treatment. At T2, 272 out of 321 on first and second line (84.7%) suppressed below 1000 copies/ml and the HIV DR prevention rate was 70.1%, just within the WHO threshold of ≥ 70%. The proportion of participants with potential HIVDR was 20.9%, which is higher than the 18.8% based on pooled analyses from African studies. Of the 35 patients with mutations at T2, 80% had M184V/I, 65.7% Y181C, and 48.6% (54.8% excluding those not on Tenofovir) had K65R mutations. 22.9% had Thymidine Analogue Mutations (TAMs). Factors significantly associated with HIVDR prevention at T2 were: baseline viral load (VL) <100,000 copies/ml [Adjusted odds ratio (AOR) 3.13, 95% confidence interval (CI): 1.36-7.19] and facility. Independent baseline predictors for HIVDR mutations at T2 were: CD4 count < 250 cells/μl (AOR 2.80, 95% CI: 1.08-7.29) and viral load ≥ 100,000 copies/ml (AOR 2.48, 95% CI: 1.00-6.14). Strengthening defaulter tracing, intensified follow-up for patients with low CD4 counts and/or high VL at ART initiation together with early treatment initiation above 250 CD4 cells/ul and adequate patient counselling would improve ART efficacy and HIVDR prevention. The high rate of K65R and TAMs could compromise second line regimens including NRTIs.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acquired immune deficiency syndrome / Adult / AIDS / Anti-HIV Agents - therapeutic use / Antiretroviral agents / Antiretroviral drugs / Antiretroviral therapy / Antiretroviral Therapy, Highly Active / CD4 antigen / Confidence intervals / Development and progression / Drug resistance / Drug Resistance, Viral / Drug therapy / Female / Genotyping / Highly active antiretroviral therapy / HIV / HIV infections / HIV Infections - drug therapy / HIV Infections - epidemiology / HIV Infections - virology / HIV-1 - drug effects / Human immunodeficiency virus / Humans / Male / Middle Aged / Mutation / Patient outcomes / Patients / Prevention / Prognosis / Prospective Studies / Tenofovir / Therapy / Thymidine / Uganda - epidemiology / Viral Load