title: Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Amsterdam Institute for Global Health and Development, Department of Global Health.
authors.forename: T Sonia
authors.initials: TS
authors.lastname: Boender
authors.affiliation: 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.
authors.forename: Raph L
authors.initials: RL
authors.lastname: Hamers
authors.affiliation: Amsterdam Institute for Global Health and Development, Department of Global Health.
authors.forename: Pascale
authors.initials: P
authors.lastname: Ondoa
authors.affiliation: Newlands Clinic, Harare, Zimbabwe.
authors.forename: Maureen
authors.initials: M
authors.lastname: Wellington
authors.affiliation: Newlands Clinic, Harare, Zimbabwe.
authors.forename: Cleophas
authors.initials: C
authors.lastname: Chimbetete
authors.affiliation: Lusaka Trust Hospital.
authors.forename: Margaret
authors.initials: M
authors.lastname: Siwale
authors.affiliation: Coptic Hospital, Lusaka, Zambia.
authors.forename: Eman E F
authors.initials: EE
authors.lastname: Labib Maksimos
authors.affiliation: Joint Clinical Research Centre, Kampala, Uganda.
authors.forename: Sheila N
authors.initials: SN
authors.lastname: Balinda
authors.affiliation: Joint Clinical Research Centre, Kampala, Uganda.
authors.forename: Cissy M
authors.initials: CM
authors.lastname: Kityo
authors.affiliation: Department of Haematology & Blood transfusion, College of Medicine of the University of Lagos, Nigeria.
authors.forename: Titilope A
authors.initials: TA
authors.lastname: Adeyemo
authors.affiliation: Department of Haematology & Blood transfusion, College of Medicine of the University of Lagos, Nigeria.
authors.forename: Alani Sulaimon
authors.initials: AS
authors.lastname: Akanmu
authors.affiliation: Coast Province General Hospital, Mombasa, Kenya.
authors.forename: Kishor
authors.initials: K
authors.lastname: Mandaliya
authors.affiliation: Muelmed Hospital, Pretoria.
authors.forename: Mariette E
authors.initials: ME
authors.lastname: Botes
authors.affiliation: Department of Molecular Medicine and Haematology, University of the Witwatersrand, and the National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Wendy
authors.initials: W
authors.lastname: Stevens
authors.affiliation: Amsterdam Institute for Global Health and Development, Department of Global Health.
authors.forename: Tobias F
authors.initials: TF
authors.lastname: Rinke de Wit
authors.affiliation: 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.
authors.forename: Kim C E
authors.initials: KC
authors.lastname: Sigaloff
mesh_terms: D000293:Adolescent; D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D017320:HIV Protease Inhibitors
keywords: HIV-1; drug resistance; protease inhibitor; second-line antiretroviral therapy; sub-Saharan Africa