title: Short communication: east meets west: a description of HIV-1 drug resistance mutation patterns of patients failing first line therapy in PEPFAR clinics from Uganda and Nigeria.
abstract: HIV-1 viral load (VL) monitoring is recommended but seldom performed in resource-constrained countries. An evaluation of patients receiving first-line antiretroviral therapy in a multicountry PEPFAR program (RV288) was performed to determine the rates and predictors of virologic suppression. Resistance data from treatment failures are available from Uganda and Nigeria. Each country enrolled 325 subjects into this cross-sectional study. Subjects on first-line therapy were randomly selected for HIV RNA testing (viral load). Regimens included efavirenz or nevirapine with zidovudine/lamivudine or tenofovir/lamivudine. VL was determined from plasma using the Roche COBAS TaqMan HIV-1 Test, High Pure System v1.0 (47 copies/ml). Genotypic resistance testing was performed on samples with VL>1,000 copies/ml. From Uganda, 85% of subjects were undetectable while 7% (23/325) had VL>1,000 copies/ml. The HIV-1 subtype distribution was as follows: A=47.6%, C=14.3%, and D=38.1%. No resistance mutations were found in 14% of subjects. All subjects with resistance had the M184V mutation. Of subjects failing a zidovudine regimen less than 1 year, 88% (7/8) had no thymidine analogue mutations (TAMs), compared to 50% (4/8) failing greater than 1 year. Four subjects (25%) had more than two mutations from the TAM-1 pathway (41L, 210W, 215Y). In Nigeria, 82% were undetectable while 14% (45/325) had VL>1,000 copies/ml. HIV-1 subtype distribution was as follows: 62.8%=CRF02_AG, 34%=pure G, and 2.8%=A. Of the 35 genotyped subjects, 14% (5/35) had no resistance mutations. Of the remainder, 10% (3/30) had no nucleoside analogue mutations while 33% (10/30) had only M184V along with nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations. Forty percent (10/25) of subjects on zidovudine failed without TAMs. Another 25% (5/25) of subjects failing on zidovudine had more than two TAM-1 mutations. Individuals failing first-line antiretroviral therapy (ART) may retain sensitivity to one or more nucleoside analogues from the regimen. Knowledge of drug resistance patterns allow for selection of drugs that can be recycled in future regimens. Accumulation of resistance mutations may compromise future treatment options.
authors.affiliation: 1 Global Health Programs, U.S. Military HIV Research Program (MHRP)/Walter Reed Army Institute of Research (WRAIR) , Bethesda, Maryland.
authors.forename: Keith W
authors.initials: KW
authors.lastname: Crawford
authors.forename: Salim
authors.initials: S
authors.lastname: Wakabi
authors.forename: Hannah
authors.initials: H
authors.lastname: Kibuuka
authors.forename: Fred
authors.initials: F
authors.lastname: Magala
authors.forename: Babajide
authors.initials: B
authors.lastname: Keshinro
authors.forename: Ifeanyi
authors.initials: I
authors.lastname: Okoye
authors.forename: Ezekiel
authors.initials: E
authors.lastname: Akintunde
authors.forename: Tiffany E
authors.initials: TE
authors.lastname: Hamm
mesh_terms: D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral; D060005:Genotyping Techniques / Q000379:methods; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D020125:Mutation, Missense; D009549:Nigeria; D017211:Treatment Failure; D014454:Uganda; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D044966:Anti-Retroviral Agents; D014764:Viral Proteins