Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda.
OBJECTIVE
To analyze antiretroviral drug susceptibility in HIV from recently infected adults in Rakai, Uganda, prior to the availability of antiretroviral drug treatment.


METHODS
Samples obtained at the time of HIV seroconversion (1998-2003) were analyzed using the GeneSeq HIV and PhenoSense HIV assays (Monogram Biosciences, Inc., South San Francisco, California, USA).


RESULTS
Test results were obtained for 104 samples (subtypes: 26A, 1C, 66D, 9A/D, 1C/D, 1 intersubtype recombinant). Mutations used for genotypic surveillance of transmitted antiretroviral drug resistance were identified in six samples: three had nucleoside reverse transcriptase inhibitor (NRTI) surveillance mutations (two had M41L, one had K219R), and three had protease inhibitor surveillance mutations (I47V, F53L, N88D); none had nonnucleoside reverse transcriptase inhibitor (NNRTI) surveillance mutations. Other resistance-associated mutations were identified in some samples. However, none of the samples had a sufficient number of mutations to predict reduced antiretroviral drug susceptibility. Ten (9.6%) of the samples had reduced phenotypic susceptibility to at least one drug (one had partial susceptibility to didanosine, one had nevirapine resistance, and eight had resistance or partial susceptibility to at least one protease inhibitor). Fifty-three (51%) of the samples had hypersusceptibility to at least one drug (seven had zidovudine hypersusceptibility, 28 had NNRTI hypersusceptibility, 34 had protease inhibitor hypersusceptibility). Delavirdine hypersusceptibility was more frequent in subtype A than D. In subtype D, efavirenz hypersusceptibility was associated with substitutions at codon 11 in HIV-reverse transcriptase.


CONCLUSIONS
Phenotyping detected reduced antiretroviral drug susceptibility and hypersusceptibility in HIV from some antiretroviral-naive Ugandan adults that was not predicted by genotyping. Phenotyping may complement genotyping for analysis of antiretroviral drug susceptibility in populations with nonsubtype B HIV infection.
Eshleman
Susan H
SH
Department of Pathology, Johns Hopkins University School of Medicine, 646 Ross Bldg., 720 Rutland Ave., Baltimore, MD 21205, USA. seshlem@jhmi.edu
Laeyendecker
Oliver
O
Parkin
Neil
N
Huang
Wei
W
Chappey
Colombe
C
Paquet
Agnes C
AC
Serwadda
David
D
Reynolds
Steven J
SJ
Kiwanuka
Noah
N
Quinn
Thomas C
TC
Gray
Ronald
R
Wawer
Maria
M
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D004198:Disease Susceptibility / Q000821:virology; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D014454:Uganda