TY - JOUR
T1 - Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda
AU - Kaleebu, Pontiano
AU - Kirungi, Wilford
AU - Watera, Christine
AU - Asio, Juliet
AU - Lyagoba, Fred
AU - Lutalo, Tom
AU - Kapaata, Anne A
AU - Nanyonga, Faith
AU - Parry, Chris M
AU - Magambo, Brian
AU - Nazziwa, Jamirah
AU - Nannyonjo, Maria
AU - Hughes, Peter
AU - Hladik, Wolfgang
AU - Ruberantwari, Anthony
AU - Namuwenge, Norah
AU - Musinguzi, Joshua
AU - Downing, Robert
AU - Katongole-Mbidde, Edward
AU - HIV Drug Resistance Working group
PY - 2015
Y1 - 2015
N2 - BACKGROUND: With the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR).METHODS: 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.RESULTS: 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).CONCLUSION: 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.
AB - BACKGROUND: With the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR).METHODS: 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.RESULTS: 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).CONCLUSION: 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.
KW - Adult
KW - Anti-HIV Agents
KW - Antiretroviral Therapy, Highly Active
KW - Drug Resistance, Viral
KW - Female
KW - HIV Infections
KW - HIV-1
KW - Humans
KW - Male
KW - Middle Aged
KW - Prognosis
KW - Prospective Studies
KW - Uganda
KW - Viral Load
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
KW - Research Support, U.S. Gov't, Non-P.H.S.
U2 - 10.1371/journal.pone.0145536
DO - 10.1371/journal.pone.0145536
M3 - Article
C2 - 26700639
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 12
M1 - e0145536
ER -