Prevalence and risk factors for developing K65R mutations among HIV-1 infected patients who fail an initial regimen of fixed-dose combination of stavudine, lamivudine, and nevirapine.
BACKGROUND
A fixed-dose combination of stavudine, lamivudine, and nevirapine (d4T/3TC/NVP) is extensively used as initial antiretroviral regimen in developing countries. K65R mutations that occur after failing this regimen prevent the use of tenofovir, didanosine, and abcavir in the second-line regimen.


OBJECTIVE
To determine the prevalence and risk factors of K65R mutations after failing d4T/3TC/NVP.


METHODS
Genotypic resistance testing was conducted among HIV-1 infected patients who experienced virological failure with an initial regimen of d4T/3TC/NVP.


RESULTS
There were 122 patients who received antiretroviral therapy (ART) for a median (IQR) duration of 19 (13-27) months. Median (IQR) CD4 cell count and plasma HIV-1 RNA at virological failure was 174 (109-264) cells/mm(3) and 4.0 (3.7-4.6)log copies/mL, respectively. The prevalence of K65R mutations was 7%. Patients with K65R mutations had higher plasma HIV-1 RNA at virological failure compared to patients without K65R mutations (4.9log copies/mL vs. 4.0log copies/mL, p=0.001). By logistic regression analysis only plasma HIV-1 RNA at failure correlated with the occurrence of K65R mutations [OR 4.2 (95% CI, 1.5-11.2) per 0.5log copies/mL increment of HIV-1 RNA].


CONCLUSIONS
Seven percent of patients had K65R mutations after failing an initial d4T/3TC/NVP regimen. Tenofovir, didanosine, and abcavir cannot be used in second-line regimen for these patients. HIV-1 RNA at the time that virological failure was detected correlated with the occurrence of K65R mutations.
Sungkanuparph
Somnuek
S
Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama 6 Road, Bangkok 10400, Thailand. rasuy@mahidol.ac.th
Manosuthi
Weerawat
W
Kiertiburanakul
Sasisopin
S
Saekang
Nipa
N
Pairoj
Wantanit
W
Chantratita
Wasun
W
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics*; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D020125:Mutation, Missense; D019829:Nevirapine / Q000627:therapeutic use*; D015995:Prevalence; D012367:RNA, Viral / Q000097:blood; D012307:Risk Factors; D018119:Stavudine / Q000627:therapeutic use*; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine