TY - JOUR
T1 - Pretreatment HIV drug resistance increases regimen switches in sub-Saharan Africa
AU - Boender, T. Sonia
AU - Hoenderboom, Bernice M.
AU - Sigaloff, Kim C. E.
AU - Hamers, Raph L.
AU - Wellington, Maureen
AU - Shamu, Tinei
AU - Siwale, Margaret
AU - Labib Maksimos, Eman E. F.
AU - Nankya, Immaculate
AU - Kityo, Cissy M.
AU - Adeyemo, Titilope A.
AU - Akanmu, Alani Sulaimon
AU - Mandaliya, Kishor
AU - Botes, Mariette E.
AU - Ondoa, Pascale
AU - Rinke de Wit, Tobias F.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - After the scale-up of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection in Africa, increasing numbers of patients have pretreatment drug resistance. In a large multicountry cohort of patients starting standard first-line ART in six African countries, pol genotyping was retrospectively performed if viral load (VL) ≥1000 cps/mL. Pretreatment drug resistance was defined as a decreased susceptibility to ≥1 prescribed drug. We assessed the effect of pretreatment drug resistance on all-cause mortality, new AIDS events and switch to second-line ART due to presumed treatment failure, using Cox models. Among 2579 participants for whom a pretreatment genotype was available, 5.5% had pretreatment drug resistance. Pretreatment drug resistance was associated with an increased risk of regimen switch (adjusted hazard ratio [aHR] 3.80; 95% confidence interval [CI], 1.49-9.68; P = .005) but was not associated with mortality (aHR 0.75, 95% CI, .24-2.35; P = .617) or new AIDS events (aHR 1.06, 95% CI, .68-1.64; P = .807). During three years of follow up, 106 (4.1%) participants switched to second-line, of whom 18 (17.0%) switched with VL < 1000 cps/mL, 7 (6.6%) with VL ≥ 1000 cps/mL and no drug resistance mutations (DRMs), 46 (43.4%) with VL ≥ 1000 cps/mL and ≥1 DRMs; no HIV RNA data was available for 32 (30.2%) participants. Given rising pretreatment HIV drug resistance levels in sub-Saharan Africa, these findings underscore the need for expanded access to second-line ART. VL monitoring can improve the accuracy of failure detection and efficiency of switching practices
AB - After the scale-up of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection in Africa, increasing numbers of patients have pretreatment drug resistance. In a large multicountry cohort of patients starting standard first-line ART in six African countries, pol genotyping was retrospectively performed if viral load (VL) ≥1000 cps/mL. Pretreatment drug resistance was defined as a decreased susceptibility to ≥1 prescribed drug. We assessed the effect of pretreatment drug resistance on all-cause mortality, new AIDS events and switch to second-line ART due to presumed treatment failure, using Cox models. Among 2579 participants for whom a pretreatment genotype was available, 5.5% had pretreatment drug resistance. Pretreatment drug resistance was associated with an increased risk of regimen switch (adjusted hazard ratio [aHR] 3.80; 95% confidence interval [CI], 1.49-9.68; P = .005) but was not associated with mortality (aHR 0.75, 95% CI, .24-2.35; P = .617) or new AIDS events (aHR 1.06, 95% CI, .68-1.64; P = .807). During three years of follow up, 106 (4.1%) participants switched to second-line, of whom 18 (17.0%) switched with VL < 1000 cps/mL, 7 (6.6%) with VL ≥ 1000 cps/mL and no drug resistance mutations (DRMs), 46 (43.4%) with VL ≥ 1000 cps/mL and ≥1 DRMs; no HIV RNA data was available for 32 (30.2%) participants. Given rising pretreatment HIV drug resistance levels in sub-Saharan Africa, these findings underscore the need for expanded access to second-line ART. VL monitoring can improve the accuracy of failure detection and efficiency of switching practices
KW - HIV-1 drug resistance
KW - antiretroviral therapy
KW - mortality
KW - regimen switch
KW - sub-Saharan Africa
UR - http://www.scopus.com/inward/record.url?scp=84952049497&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/cid/civ656
DO - https://doi.org/10.1093/cid/civ656
M3 - Article
C2 - 26240203
SN - 1058-4838
VL - 61
SP - 1749
EP - 1758
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 11
ER -