Resistance profiles after different periods of exposure to a first-line antiretroviral regimen in a Cameroonian cohort of HIV type-1-infected patients.
BACKGROUND
The lack of HIV type-1 (HIV-1) viral load (VL) monitoring in resource-limited settings might favour the accumulation of resistance mutations and thus hamper second-line treatment efficacy. We investigated the factors associated with resistance after the initiation of antiretroviral therapy (ART) in the absence of virological monitoring.


METHODS
Cross-sectional VL sampling of HIV-1-infected patients receiving first-line ART (nevirapine or efavirenz plus stavudine or zidovudine plus lamivudine) was carried out; those with a detectable VL were genotyped.


RESULTS
Of the 573 patients undergoing VL sampling, 84 were genotyped. The mean number of nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) mutations increased with the duration of ART exposure (P=0.02). Multivariable analysis showed that patients with a CD4+ T-cell count < or =50 cells/mm(3) at ART initiation (baseline) had a higher mean number of both NRTI and non-NRTI (NNRTI) mutations than those with a baseline CD4+ T-cell count >50 cells/mm(3) (2.10 versus 0.56; P<0.0001; and 1.65 versus 0.76; P=0.005, respectively). A baseline CD4+ T-cell count < or =50 cells/mm(3) predicted > or =1 NRTI mutation (adjusted odds ratio [AOR] 7.49, 95% confidence interval [CI] 2.20-32.14), > or =1 NNRTI mutation (AOR 4.25, 95% CI 1.36-15.48), > or =1 thymidine analogue mutation (AOR 8.45, 95% CI 2.16-40.16) and resistance to didanosine (AOR 6.36, 95% CI 1.49-32.29) and etravirine (AOR 4.72, 95% CI 1.53-15.70).


CONCLUSIONS
Without VL monitoring, the risk of drug resistance increases with the duration of ART and is associated with lower CD4+ T-cell counts at ART initiation. These data might help define strategies to preserve second-line treatment options in resource-limited settings.
Soria
Alessandro
A
Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy. a.soria@hsgerardo.org
Porten
Klaudia
K
Fampou-Toundji
Jean-Calvin
JC
Galli
Laura
L
Mougnutou
Rose
R
Buard
Vincent
V
Kfutwah
Anfumbom
A
Vessière
Aurelia
A
Rousset
Dominique
D
Teck
Roger
R
Calmy
Alexandra
A
Ciaffi
Laura
L
Lazzarin
Adriano
A
Gianotti
Nicola
N
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002163:Cameroon / Q000453:epidemiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019562:Viral Load
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors