title: HIV-1 drug resistance in antiretroviral-naive individuals in sub-Saharan Africa after rollout of antiretroviral therapy: a multicentre observational study.
abstract: BACKGROUND
  There are few data on the epidemiology of primary HIV-1 drug resistance after the roll-out of antiretroviral treatment (ART) in sub-Saharan Africa. We aimed to assess the prevalence of primary resistance in six African countries after ART roll-out and if wider use of ART in sub-Saharan Africa is associated with rising prevalence of drug resistance.
  
  
  METHODS
  We did a cross-sectional study in antiretroviral-naive adults infected with HIV-1 who had not started first-line ART, recruited between 2007 and 2009 from 11 regions in Kenya, Nigeria, South Africa, Uganda, Zambia, and Zimbabwe. We did population-based sequencing of the pol gene on plasma specimens with greater than 1000 copies per mL of HIV RNA. We identified drug-resistance mutations with the WHO list for transmitted resistance. The prevalence of sequences containing at least one drug-resistance mutation was calculated accounting for the sampling weights of the sites. We assessed the risk factors of resistance with multilevel logistic regression with random coefficients.
  
  
  RESULTS
  2436 (94.1%) of 2590 participants had a pretreatment genotypic resistance result. 1486 participants (57.4%) were women, 1575 (60.8%) had WHO clinical stage 3 or 4 disease, and the median CD4 count was 133 cells per μL (IQR 62-204). Overall sample-weighted drug-resistance prevalence was 5.6% (139 of 2436; 95% CI 4.6-6.7), ranging from 1.1% (two of 176; 0.0-2.7) in Pretoria, South Africa, to 12.3% (22 of 179; 7.5-17.1) in Kampala, Uganda. The pooled prevalence for all three Ugandan sites was 11.6% (66 of 570; 8.9-14.2), compared with 3.5% (73 of 1866; 2.5-4.5) for all other sites. Drug class-specific resistance prevalence was 2.5% (54 of 2436; 1.8-3.2) for nucleoside reverse-transcriptase inhibitors (NRTIs), 3.3% (83 of 2436; 2.5-4.2) for non-NRTIs (NNRTIs), 1.3% (31 of 2436; 0.8-1.8) for protease inhibitors, and 1.2% (25 of 2436; 0.7-1.7) for dual-class resistance to NRTIs and NNRTIs. The most common drug-resistance mutations were K103N (43 [1.8%] of 2436), thymidine analogue mutations (33 [1.6%] of 2436), M184V (25 [1.2%] of 2436), and Y181C/I (19 [0.7%] of 2436). The odds ratio for drug resistance associated with each additional year since the start of the ART roll-out in a region was 1.38 (95% CI 1.13-1.68; p=0.001).
  
  
  CONCLUSIONS
  The higher prevalence of primary drug resistance in Uganda than in other African countries is probably related to the earlier start of ART roll-out in Uganda. Resistance surveillance and prevention should be prioritised in settings where ART programmes are scaled up.
  
  
  BACKGROUND
  Ministry of Foreign Affairs of the Netherlands.
authors.affiliation: PharmAccess Foundation, Department of Global Health, Academic Medical Centre of University of Amsterdam, Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands. r.hamers@amc-cpcd.org
authors.forename: Raph L
authors.initials: RL
authors.lastname: Hamers
authors.forename: Carole L
authors.initials: CL
authors.lastname: Wallis
authors.forename: Cissy
authors.initials: C
authors.lastname: Kityo
authors.forename: Margaret
authors.initials: M
authors.lastname: Siwale
authors.forename: Kishor
authors.initials: K
authors.lastname: Mandaliya
authors.forename: Francesca
authors.initials: F
authors.lastname: Conradie
authors.forename: Mariette E
authors.initials: ME
authors.lastname: Botes
authors.forename: Maureen
authors.initials: M
authors.lastname: Wellington
authors.forename: Akin
authors.initials: A
authors.lastname: Osibogun
authors.forename: Kim C E
authors.initials: KC
authors.lastname: Sigaloff
authors.forename: Immaculate
authors.initials: I
authors.lastname: Nankya
authors.forename: Rob
authors.initials: R
authors.lastname: Schuurman
authors.forename: Ferdinand W
authors.initials: FW
authors.lastname: Wit
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Stevens
authors.forename: Michèle
authors.initials: M
authors.lastname: van Vugt
authors.forename: Tobias F Rinke
authors.initials: TF
authors.lastname: de Wit
mesh_terms: D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D000368:Aged; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D044966:Anti-Retroviral Agents / Q000008:administration & dosage; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009549:Nigeria / Q000453:epidemiology; D011159:Population Surveillance; D015995:Prevalence; D011446:Prospective Studies; D013019:South Africa / Q000453:epidemiology; D013936:Thymidine / Q000031:analogs & derivatives / Q000235:genetics; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load / Q000187:drug effects; D015024:Zambia / Q000453:epidemiology; D015030:Zimbabwe / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D013936:Thymidine