HIV type 1 subtype diversity and drug resistance among HIV type 1-infected Kenyan patients initiating antiretroviral therapy.
The treatment of HIV-1 infection with antiretroviral drugs has greatly improved the survival of those who are infected. However, HIV-1 diversity and drug resistance are major challenges in patient management, especially in resource-poor countries. To evaluate HIV-1 genetic diversity and drug resistance-associated mutations among drug-naive patients in Kenya prior to antiretroviral therapy (ART), a genetic analysis of HIV-1 pol-RT and env-gp41 was performed on samples collected from 53 (18 males and 35 females) consenting patients between April and June 2005. The average age, baseline CD4(+) T cell counts, and viral loads were 38 (range, 24-62) years, 475 (range, 203-799) cells/mm(3), and 4.7 (range, 3.4-5.9) log(10) copies/ml, respectively. Phylogenetic analysis revealed that 40 samples (75.5%) were concordant subtypes for the two genes and 13 (24.5%) were discordant, suggesting possible recombination and/or dual infections. Prevalent subtypes included A1/A1(pol-RT/env-gp41), 31 (58.5%); D/D, 9 (16.9%); A1/C, 2 (3.8%); A1/D, 4 (7.5%); G/A1, 2 (3.8%); A1/A2, 1 (1.9%); C/A1, 2 (3.8%); D/A1, 1(1.9%); and D/A2, 1 (1.9%). Major reverse transcriptase inhibitor (RTI) resistance-associated mutations were found in four patients (7.5%). Of these patients, three had nucleoside RTI resistance mutations, such as M184V, K65R, D67N, K70R, and K219Q. Nonnucleoside RTI resistance-associated mutations K103N and Y181C were detected in three patients and one patient, respectively. Multiple drug resistance mutations were observed in this drug-naive population. With increasing numbers of patients that require treatment and the rapid upscaling of ART in Kenya, HIV-1 drug resistance testing is recommended before starting treatment in order to achieve better clinical outcomes.
Lihana
Raphael W
RW
Center for Virus Research, Kenya Medical Research Institute, Nairobi, Kenya. Rlihana@kemri.org
Khamadi
Samoel A
SA
Lubano
Kizito
K
Lwembe
Raphael
R
Kiptoo
Michael K
MK
Lagat
Nancy
N
Kinyua
Joyceline G
JG
Okoth
Fredrick A
FA
Songok
Elijah M
EM
Makokha
Ernest P
EP
Ichimura
Hiroshi
H
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D005260:Female; D015752:Genes, env / Q000187:drug effects / Q000235:genetics; D015751:Genes, pol / Q000187:drug effects / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D010802:Phylogeny; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019562:Viral Load
D018894:Reverse Transcriptase Inhibitors