Low prevalence of primary mutations associated with drug resistance in antiviral-naive patients at therapy initiation.
OBJECTIVE
To assess the prevalence of mutations in the reverse-transcriptase (RT) and protease (PR) region in a cohort of chronically-infected HIV-positive patients requiring highly active antiretroviral therapy (HAART).


METHODS
The study included 347 patients enrolled in the Italian Cohort of Antiretroviral Naive patients (I.CO.NA) who had to initiate HAART. The whole PR-region, and amino acids 1-320 of RT-region were sequenced from plasma samples at baseline.


RESULTS
Median CD4-lymphocytes and HIV-RNA at baseline were 231 x 10(6) cells/l and 4.89 log(10) copies/ml; 307 of 347 (88.5%) patients carried no mutations in the RT region, whereas 40 (11.5%) carried one or more mutations associated with resistance to nucleoside-RT inhibitor (NRTI) (7.8%), or non-nucleoside-RTI (NNRTI) (4.9%), with four patients carrying mutations to both classes. Among mutations associated with high-level resistance to RTI, T215Y was found in only two patients, M184V in two cases, T69D and T215C in other two cases (one each), and K103N in only one patient, for a total of six patients (one carrying both T215Y and M184V) (1.7%). Seventy-six patients (21.9%) carried no mutations in the PR region, whereas 271 (78.1%) had one or more mutations. Primary mutations associated with substantial resistance to protease inhibitors were found in only five of 347 patients (1.4%) (M46V/L, I54V, V82A/I); all the other patients carried only secondary mutations (L10F/I/V, M36I, L63P, A71T/V, V77I).


CONCLUSIONS
Prevalence of mutations associated with high-level resistance to antiretroviral drugs is low in HIV-infected patients with long-term infection. This suggests no preclusion in principle to any antiretroviral drug at the time of decision of the first therapeutic regimen.
Perno
Carlo Federico
CF
IRCCS L. Spallanzani Hospital, Via Portuense 292, 00149 Rome, Italy. cf.perno@uniroma2.it
Cozzi-Lepri
Alessandro
A
Balotta
Claudia
C
Bertoli
Ada
A
Violin
Michela
M
Monno
Laura
L
Zauli
Tiziano
T
Montroni
Maria
M
Ippolito
Giuseppe
G
d'Arminio-Monforte
Antonella
A
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006679:HIV Seropositivity / Q000453:epidemiology / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D015995:Prevalence; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D019562:Viral Load
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors