TY - JOUR
T1 - Pretreatment HIV Drug Resistance and HIV-1 Subtype C Are Independently Associated with Virologic Failure
T2 - Results from the Multinational PEARLS (ACTG A5175) Clinical Trial
AU - Kantor, Rami
AU - Smeaton, Laura
AU - Vardhanabhuti, Saran
AU - Hudelson, Sarah E.
AU - Wallis, Carol L.
AU - Tripathy, Srikanth
AU - Morgado, Mariza G.
AU - Saravanan, Shanmugham
AU - Balakrishnan, Pachamuthu
AU - Reitsma, Marissa
AU - Hart, Stephen
AU - Mellors, John W.
AU - Halvas, Elias
AU - Grinsztejn, Beatriz
AU - Hosseinipour, Mina C.
AU - Kumwenda, Johnstone
AU - La Rosa, Alberto
AU - Lalloo, Umesh G.
AU - Lama, Javier R.
AU - Rassool, Mohammed
AU - Santos, Breno R.
AU - Supparatpinyo, Khuanchai
AU - Hakim, James
AU - Flanigan, Timothy
AU - Kumarasamy, Nagalingeswaran
AU - Campbell, Thomas B.
AU - Eshleman, Susan H.
N1 - Publisher Copyright:
© 2015 The Author.
PY - 2015/5/15
Y1 - 2015/5/15
N2 - Background. Evaluation of pretreatment HIV genotyping is needed globally to guide treatment programs. We examined the association of pretreatment (baseline) drug resistance and subtype with virologic failure in a multinational, randomized clinical trial that evaluated 3 antiretroviral treatment (ART) regimens and included resource-limited setting sites. Methods. Pol genotyping was performed in a nested case-cohort study including 270 randomly sampled participants (subcohort), and 218 additional participants failing ART (case group). Failure was defined as confirmed viral load (VL) >1000 copies/mL. Cox proportional hazards models estimated resistance-failure association. Results. In the representative subcohort (261/270 participants with genotypes; 44% women; median age, 35 years; median CD4 cell count, 151 cells/μL; median VL, 5.0 log10 copies/mL; 58% non-B subtypes), baseline resistance occurred in 4.2%, evenly distributed among treatment arms and subtypes. In the subcohort and case groups combined (466/488 participants with genotypes), used to examine the association between resistance and treatment failure, baseline resistance occurred in 7.1% (9.4% with failure, 4.3% without). Baseline resistance was significantly associated with shorter time to virologic failure (hazard ratio [HR], 2.03; P =. 035), and after adjusting for sex, treatment arm, sex-treatment arm interaction, pretreatment CD4 cell count, baseline VL, and subtype, was still independently associated (HR, 2.1; P =. 05). Compared with subtype B, subtype C infection was associated with higher failure risk (HR, 1.57; 95% confidence interval [CI], 1.04-2.35), whereas non-B/C subtype infection was associated with longer time to failure (HR, 0.47; 95% CI,. 22-.98). Conclusions. In this global clinical trial, pretreatment resistance and HIV-1 subtype were independently associated with virologic failure. Pretreatment genotyping should be considered whenever feasible. Clinical Trials Registration. NCT00084136.
AB - Background. Evaluation of pretreatment HIV genotyping is needed globally to guide treatment programs. We examined the association of pretreatment (baseline) drug resistance and subtype with virologic failure in a multinational, randomized clinical trial that evaluated 3 antiretroviral treatment (ART) regimens and included resource-limited setting sites. Methods. Pol genotyping was performed in a nested case-cohort study including 270 randomly sampled participants (subcohort), and 218 additional participants failing ART (case group). Failure was defined as confirmed viral load (VL) >1000 copies/mL. Cox proportional hazards models estimated resistance-failure association. Results. In the representative subcohort (261/270 participants with genotypes; 44% women; median age, 35 years; median CD4 cell count, 151 cells/μL; median VL, 5.0 log10 copies/mL; 58% non-B subtypes), baseline resistance occurred in 4.2%, evenly distributed among treatment arms and subtypes. In the subcohort and case groups combined (466/488 participants with genotypes), used to examine the association between resistance and treatment failure, baseline resistance occurred in 7.1% (9.4% with failure, 4.3% without). Baseline resistance was significantly associated with shorter time to virologic failure (hazard ratio [HR], 2.03; P =. 035), and after adjusting for sex, treatment arm, sex-treatment arm interaction, pretreatment CD4 cell count, baseline VL, and subtype, was still independently associated (HR, 2.1; P =. 05). Compared with subtype B, subtype C infection was associated with higher failure risk (HR, 1.57; 95% confidence interval [CI], 1.04-2.35), whereas non-B/C subtype infection was associated with longer time to failure (HR, 0.47; 95% CI,. 22-.98). Conclusions. In this global clinical trial, pretreatment resistance and HIV-1 subtype were independently associated with virologic failure. Pretreatment genotyping should be considered whenever feasible. Clinical Trials Registration. NCT00084136.
KW - HIV
KW - clinical trial.
KW - drug resistance
KW - subtype
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U2 - 10.1093/cid/civ102
DO - 10.1093/cid/civ102
M3 - Article
C2 - 25681380
AN - SCOPUS:84929208014
SN - 1058-4838
VL - 60
SP - 1541
EP - 1549
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 10
ER -