TY - JOUR
T1 - Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa
AU - Boender, T. Sonia
AU - Hamers, Raph L.
AU - Ondoa, Pascale
AU - Wellington, Maureen
AU - Chimbetete, Cleophas
AU - Siwale, Margaret
AU - Labib Maksimos, Eman E.F.
AU - Balinda, Sheila N.
AU - Kityo, Cissy M.
AU - Adeyemo, Titilope A.
AU - Akanmu, Alani Sulaimon
AU - Mandaliya, Kishor
AU - Botes, Mariette E.
AU - Stevens, Wendy
AU - Rinke De Wit, Tobias F.
AU - Sigaloff, Kim C.E.
PY - 2016/9/15
Y1 - 2016/9/15
N2 - Background. As antiretroviral therapy (ART) programs in sub-Saharan Africa mature, increasing numbers of persons with human immunodeficiency virus (HIV) infection will experience treatment failure, and require second- or third-line ART. Data on second-line failure and development of protease inhibitor (PI) resistance in sub-Saharan Africa are scarce. Methods. HIV-1-infected adults were included if they received >180 days of PI-based second-line ART. We assessed risk factors for having a detectable viral load (VL, ≥400 cps/mL) using Cox models. If VL was ≥1000 cps/mL, genotyping was performed. Results. Of 227 included participants, 14.6%, 15.2% and 11.1% had VLs ≥400 cps/mL at 12, 24, and 36 months, respectively. Risk factors for a detectable VL were as follows: exposure to nonstandard nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based (hazard ratio, 7.10; 95% confidence interval, 3.40-14.83; P <. 001) or PI-based (7.59; 3.02-19.07; P =. 001) first-line regimen compared with zidovudine/lamivudine/NNRTI, PI resistance at switch (6.69; 2.49-17.98; P <. 001), and suboptimal adherence (3.05; 1.71-5.42; P =. 025). Among participants with VLs ≥1000 cps/mL, 22 of 32 (69%) harbored drug resistance mutation(s), and 7 of 32 (22%) harbored PI resistance. Conclusions. Although VL suppression rates were high, PI resistance was detected in 22% of participants with VLs ≥1000 cps/mL. To ensure long-term ART success, intensified support for adherence, VL and drug resistance testing, and third-line drugs will be necessary.
AB - Background. As antiretroviral therapy (ART) programs in sub-Saharan Africa mature, increasing numbers of persons with human immunodeficiency virus (HIV) infection will experience treatment failure, and require second- or third-line ART. Data on second-line failure and development of protease inhibitor (PI) resistance in sub-Saharan Africa are scarce. Methods. HIV-1-infected adults were included if they received >180 days of PI-based second-line ART. We assessed risk factors for having a detectable viral load (VL, ≥400 cps/mL) using Cox models. If VL was ≥1000 cps/mL, genotyping was performed. Results. Of 227 included participants, 14.6%, 15.2% and 11.1% had VLs ≥400 cps/mL at 12, 24, and 36 months, respectively. Risk factors for a detectable VL were as follows: exposure to nonstandard nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based (hazard ratio, 7.10; 95% confidence interval, 3.40-14.83; P <. 001) or PI-based (7.59; 3.02-19.07; P =. 001) first-line regimen compared with zidovudine/lamivudine/NNRTI, PI resistance at switch (6.69; 2.49-17.98; P <. 001), and suboptimal adherence (3.05; 1.71-5.42; P =. 025). Among participants with VLs ≥1000 cps/mL, 22 of 32 (69%) harbored drug resistance mutation(s), and 7 of 32 (22%) harbored PI resistance. Conclusions. Although VL suppression rates were high, PI resistance was detected in 22% of participants with VLs ≥1000 cps/mL. To ensure long-term ART success, intensified support for adherence, VL and drug resistance testing, and third-line drugs will be necessary.
KW - HIV-1
KW - drug resistance
KW - protease inhibitor
KW - second-line antiretroviral therapy
KW - sub-Saharan Africa
UR - http://www.scopus.com/inward/record.url?scp=84984993524&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/infdis/jiw219
DO - https://doi.org/10.1093/infdis/jiw219
M3 - Article
C2 - 27402780
SN - 0022-1899
VL - 214
SP - 873
EP - 883
JO - Journal of infectious diseases
JF - Journal of infectious diseases
IS - 6
ER -