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J Infect Dis. 2016 Sep 15;214(6):873-83. doi: 10.1093/infdis/jiw219. Epub 2016 Jul 11.

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

Author information

1
Amsterdam Institute for Global Health and Development, Department of Global Health.
2
Amsterdam Institute for Global Health and Development, Department of Global Health Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, The Netherlands.
3
Newlands Clinic, Harare, Zimbabwe.
4
Lusaka Trust Hospital.
5
Coptic Hospital, Lusaka, Zambia.
6
Joint Clinical Research Centre, Kampala, Uganda.
7
Department of Haematology & Blood transfusion, College of Medicine of the University of Lagos, Nigeria.
8
Coast Province General Hospital, Mombasa, Kenya.
9
Muelmed Hospital, Pretoria.
10
Department of Molecular Medicine and Haematology, University of the Witwatersrand, and the National Health Laboratory Service, Johannesburg, South Africa.

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.

KEYWORDS:

HIV-1; drug resistance; protease inhibitor; second-line antiretroviral therapy; sub-Saharan Africa

PMID:
27402780
DOI:
10.1093/infdis/jiw219
[Indexed for MEDLINE]

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