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

Kaleebu, Pontiano ; Kirungi, Wilford ; Watera, Christine ; Asio, Juliet ; Lyagoba, Fred ; Lutalo, Tom ; Kapaata, Anne A ; Nanyonga, Faith ; Parry, Chris M and Magambo, Brian , et al. (2015) In PLoS ONE 10(12).
Abstract

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... (More)

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.

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Contribution to journal
publication status
published
keywords
Adult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Prognosis, Prospective Studies, Uganda, Viral Load, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
in
PLoS ONE
volume
10
issue
12
article number
e0145536
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:26700639
  • scopus:84957591891
ISSN
1932-6203
DOI
10.1371/journal.pone.0145536
language
English
LU publication?
no
id
6a292644-edcc-47a2-b4b5-084a6657f2de
date added to LUP
2018-03-22 14:03:47
date last changed
2024-02-13 17:20:13
@article{6a292644-edcc-47a2-b4b5-084a6657f2de,
  abstract     = {{<p>BACKGROUND: With the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR).</p><p>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.</p><p>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) &lt;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 &lt; 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).</p><p>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.</p>}},
  author       = {{Kaleebu, Pontiano and Kirungi, Wilford and Watera, Christine and Asio, Juliet and Lyagoba, Fred and Lutalo, Tom and Kapaata, Anne A and Nanyonga, Faith and Parry, Chris M and Magambo, Brian and Nazziwa, Jamirah and Nannyonjo, Maria and Hughes, Peter and Hladik, Wolfgang and Ruberantwari, Anthony and Namuwenge, Norah and Musinguzi, Joshua and Downing, Robert and Katongole-Mbidde, Edward}},
  issn         = {{1932-6203}},
  keywords     = {{Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Drug Resistance, Viral; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Uganda; Viral Load; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.}},
  language     = {{eng}},
  number       = {{12}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0145536}},
  doi          = {{10.1371/journal.pone.0145536}},
  volume       = {{10}},
  year         = {{2015}},
}