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Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa.

Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa.
Author Information (click to view)

Boender TS, Hamers RL, Ondoa P, Wellington M, Chimbetete C, Siwale M, Labib Maksimos EE, Balinda SN, Kityo CM, Adeyemo TA, Akanmu AS, Mandaliya K, Botes ME, Stevens W, Rinke de Wit TF, Sigaloff KC,


Boender TS, Hamers RL, Ondoa P, Wellington M, Chimbetete C, Siwale M, Labib Maksimos EE, Balinda SN, Kityo CM, Adeyemo TA, Akanmu AS, Mandaliya K, Botes ME, Stevens W, Rinke de Wit TF, Sigaloff KC, (click to view)

Boender TS, Hamers RL, Ondoa P, Wellington M, Chimbetete C, Siwale M, Labib Maksimos EE, Balinda SN, Kityo CM, Adeyemo TA, Akanmu AS, Mandaliya K, Botes ME, Stevens W, Rinke de Wit TF, Sigaloff KC,

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The Journal of infectious diseases 2016 07 11214(6) 873-83 doi 10.1093/infdis/jiw219

Abstract
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.

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