Genotypic HIV type-1 drug resistance among patients with immunological failure to first-line antiretroviral therapy in south India.
BACKGROUND
HIV type-1 (HIV-1) monitoring in resource-limited settings relies on clinical and immunological assessment. The objective of this study was to study the frequency and pattern of reverse transcriptase (RT) drug resistance among patients with immunological failure (IF) to first-line therapy.


METHODS
A cross-sectional study of 228 patients with IF was done, of which 126 were drug-naive (group A) when starting highly active antiretroviral therapy (HAART) and 102 were exposed to mono/dual therapy prior to HAART initiation (group B). A validated in-house genotyping method and Stanford interpretation was used. Means, sd, median and frequencies (as percentages) were used to indicate the patient characteristics in each group. The chi(2) test and Fisher's exact test were used to compare categorical variables as appropriate. All analyses were performed using SPSS software, version 13.0. P-values <0.05 were considered to be statistically significant.


RESULTS
RT drug resistance mutations were found in 92% and 96% of patients in groups A and B, respectively. Median (interquartile range) CD4(+) T-cell count at failure was 181 cells/microl (18-999) and time to failure was 40 months (2-100). M184V (80% versus 75%), thymidine analogue mutations (63% versus 74%), Y181C (39% versus 39%) and K103N (29% versus 39%) were predominant RT mutations in both groups. Extensive nucleoside reverse transcriptase inhibitor cross-resistance mutations were observed in 51% and 26% of patients in group B and A, respectively.


CONCLUSIONS
Alternative strategies for initial therapy and affordable viral load monitoring could reduce resistance accumulations and preserve available drugs for future options in resource-limited settings.
Vidya
Madhavan
M
YRG Centre for AIDS Research and Education, Chennai, India.
Saravanan
Shanmugam
S
Uma
Shanmugasundaram
S
Kumarasamy
Nagalingeswaran
N
Sunil
Solomon S
SS
Kantor
Rami
R
Katzenstein
David
D
Ramratnam
Bharat
B
Mayer
Kenneth H
KH
Suniti
Solomon
S
Balakrishnan
Pachamuthu
P
D000328:Adult; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D009154:Mutation; D015995:Prevalence; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D017211:Treatment Failure
D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors