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 - Background. After the scale-up of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection in Africa, increasing numbers of patients have pretreatment drug resistance. Methods. 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. Results. 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. Conclusions. 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 - Background. After the scale-up of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection in Africa, increasing numbers of patients have pretreatment drug resistance. Methods. 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. Results. 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. Conclusions. 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 - antiretroviral therapy
KW - HIV-1 drug resistance
KW - mortality
KW - regimen switch
KW - sub-Saharan Africa
UR - http://www.scopus.com/inward/record.url?scp=84952049497&partnerID=8YFLogxK
U2 - 10.1093/cid/civ656
DO - 10.1093/cid/civ656
M3 - Article
C2 - 26240203
AN - SCOPUS:84952049497
VL - 61
SP - 1749
EP - 1758
JO - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
SN - 1058-4838
IS - 11
ER -