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Prevalence of HIV-1 Drug Resistance after Virologic Failure of First HAART Regimen in South Africa: Initial Results of the South Africa Resistance Cohort Study
Vincent C. Marconi*1,2, Vincent C. Marconi*1,2, H Sunpath3, Z Lu4, M Gordon5, K Koranteng6, J Hampton3, D Ross6, E Losina4, B Walker4, D Kuritzkes1, and SARCS Team
1Brigham and Women's Hosp, Harvard Med Sch, Boston, MA, US; 2Wilford Hall US Air Force Med Ctr, Lackland AFB, TX, US; 3McCords Hosp, Durban, South Africa; 4Massachusetts Gen Hosp, Harvard Med Sch, Boston, US; 5Inkosi Albert Luthuli, Nelson Mandela Sch of Med, Durban, South Africa; and 6St Mary's Hosp, Mariannhill, South Africa
Background: Since the introduction of triple-combination ART
into South Africa
to treat HIV/AIDS, thousands of patients have been enrolled into the ARV
National Plan at clinics across the country. First-line therapy (regimen 1) consists
of lamivudine, stavudine,
and efavirenz (or nevirapine). Many patients had single- and dual-nucleoside
therapy prior to enrollment. This study examines the early experience of 2
clinics in Kwa-Zulu Natal with the goal of
understanding the prevalence of HIV-1 resistance to first-line ART and the
effectiveness of subsequent therapy.
Methods: This ongoing observational cohort study
enrolled patients with virologic failure of a first
ART regimen, defined as a plasma HIV-1 RNA (viral load) ≥1000 copies/mL. ART was determined by genotypic resistance testing
(TRUGENE); clinicians used this information to determine whether therapy should
be changed. Patients were followed for another 6 months to determine whether
the management resulted in virologic suppression. All
patients had additional adherence training.
Results: Since January 2005, of 3000 ART-treated
patients, 119 (4.0%) experienced virologic failure. Median
viral load at virologic failure was 4.26 log10 copies/mL (IQR 3.66
to 4.90 log10 copies/mL); median
CD4 cell count was 153/mm3 (IQR 104 to 229/mm3); 21.3% of
the patients had WHO stage IV disease; 45.4% were currently receiving regimen 1
at the time of failure. Of the patients with virologic
failure, 75.6% had ≥1 significant resistance mutation, 53.8% had
dual-class resistance, and 1.7% had triple-class resistance; 55.5% of the
cohort had an M184V mutation, 47.1% had K103N, and 3.4% had significant PI
mutations. Exploratory multiple logistic regression analysis identified recent
opportunistic infections (OR 3.21, 95%CI 1.17 to 8.85, p = 0.024) as a significant risk factor for virologic
failure with drug resistance in models that also adjusted for baseline age,
gender, CD4 count, WHO stage, hemoglobin, and viral load.
Conclusions: Antiretroviral drug resistance has been
detected in a growing number of South African patients with virologic
failure of first-line ART. The resistance profiles predominantly contained nucleoside
reverse transcriptase inhibitor (NRTI) and non-NRTI (NNRTI) mutations
reflecting use of the first-line regimen. This study identified recent
opportunistic infections as a major risk factor for virologic
failure with drug resistance among HIV-1-infected South African patients with
first-line ART failure. Further follow-up of this cohort is underway to
determine the effectiveness of second-line regimens in this setting.
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