HIV type 1 pol gene diversity and archived nevirapine resistance mutation in pregnant women in Rwanda.
This study aimed to find out whether genetic polymorphisms were present in positions potentially affecting susceptibility to antiretrovirals in non-B subtypes from HIV-1-infected patients in Rwanda. Viral pol gene diversity was investigated by direct sequencing in 43 treatment-naive women. In addition, 10 DNA sequences from uncultured peripheral blood mononuclear cells were analyzed 6 weeks after a single dose of nevirapine (prevention of mother-to-child transmission program). Phylogenetic analyses have shown 34 subtype A1, 6 subtype C, and 2 subtype D strains. In addition, an A/C recombinant between the protease (PR) (subtype A1) and the reverse transcriptase (RT) (subtype C) was identified. In the PR coding region, high numbers of polymorphisms were found, including substitutions in secondary PR resistance sites. PR 35D, 36I, and 37N were always present within subtype A as were PR 93L in subtype C strains. PR 10I/V, 20R, 33F, and 77V were found in subtype A whereas PR 36I was highly prevalent in subtype C strains. The A/C recombinant displayed substitutions related to resistance (PR 10, 33, 36 and RT 118). One nevirapine resistance mutation (RT 181Y/C) was found in proviral DNA after 6 weeks. In conclusion, subtypes A and C are predominant in this cohort in Rwanda. Substitutions similar to secondary protease inhibitor resistance mutations are common before treatment whereas major resistance mutation may be archived after a single dose of nevirapine. Accordingly, the hypothesis of a genetic background effect in non-B strains has to be further addressed in programs of introduction of antivirals in Africa.
Servais
Jean
J
Treatment Research AIDS Center, Kigali, Rwanda. rwa21@rwandal.com
Lambert
Christine
C
Karita
Etienne
E
Vanhove
Dirk
D
Fischer
Aurelie
A
Baurith
Therese
T
Schmit
Jean-Claude
JC
Schneider
François
F
Hemmer
Robert
R
Arendt
Vic
V
D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015751:Genes, pol / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008969:Molecular Sequence Data; D009154:Mutation; D019829:Nevirapine / Q000008:administration & dosage / Q000494:pharmacology*; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000821:virology*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D012432:Rwanda; D017422:Sequence Analysis, DNA
D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D054303:HIV Reverse Transcriptase; D016333:HIV Protease