Primary HIV-1 resistance in recently and chronically infected individuals of the Italian Cohort Naive for Antiretrovirals.
The risk of acquiring HIV-1 drug resistance at time of infection has become a public health problem following the widespread use of antiretroviral drugs in developed countries. Although a number of studies have reported data regarding the prevalence of HIV-1 primary resistance in developed countries over the past years, limited knowledge is available regarding the proportion of mutations related to drug resistance in antiretroviral naive subjects with chronic HIV-1 disease. In this study, we evaluated the prevalence of mutations in the reverse-transcriptase (RT) and protease region both in a representative group of recently HIV-1 infected subjects (n=68) and a cohort of chronically-infected HIV-positive patients (n=347) enrolled in the Italian Cohort of Antiretroviral Naive patients (I.CO.NA.). In recently infected individuals, the overall prevalence of mutations for nucleoside RTI (NRTIs) was 10/68 (14.7%). The distribution of mutations by calendar year were 0, 1 in 1996, 9, 3 in 1997 and 1, 0 in 1998 for NRTIs and protease inhibitors (PIs) respectively. Thymidine associated mutations were identified in six subjects (8.8%), five of whom had one mutation [41L, 70K (n=2), 215Y] and one had two mutations (67N+219Q). Four subjects (5.9%) showed the changes associated with resistance to lamivudine (184V or 118I). No non nucleoside-RTI (NNRTI) mutations were present in the study period. Primary PIs mutations (two 46L and two 82I) were present in four subjects (5.9%). Of note, mutations related to resistance to more than one class of antiretrovirals were present in one (1.5%). Among patients with chronic infection a large proportion (88.5%) carried no mutations in RT region, 11.5% individuals carried one or more mutations associated with resistance to NRTI (7.8%), or NNRTI (4.9%), with 4 patients carrying mutations to both classes. Among mutations associated with high-level resistance to RTI, T215Y was found in only 2 patients, M184V in 2 cases, T69D in another case, and K103N in only 1 patient, for a total of 6 patients (one carrying both T215Y and M184V) (1.7%). Primary mutations associated with substantial resistance to PIs were found in only 5/347 patients (1.4%); all the other patients carried only secondary mutations. Prevalence of mutations associated with high-level resistance to antiretroviral drugs is stable in recently infected individuals and low in patients with established HIV infection. The potential impact of transmitted mutations on the response to first regimen in individuals carrying transmitted mutations needs to be assessed by prospective studies.
Violin
M
M
Institute of Infectious and Tropical Diseases, University of Milan, L Sacco Hospital, Italy.
Forbici
F
F
Cozzi-Lepri
A
A
Velleca
R
R
Bertoli
A
A
Riva
C
C
Giannella
S
S
Manconi
P E
PE
Lazzarin
A
A
Pasquinucci
S
S
Tacconi
L
L
Carnevale
G
G
Mazzotta
F
F
Bonazzi
L
L
Montroni
M
M
Chirianni
A
A
Capobianchi
M
M
Ippolito
G
G
Moroni
M
M
Perno
C F
CF
D'Arminio-Monforte
A
A
D000208:Acute Disease; D000328:Adult; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000494:pharmacology*; D000963:Antimetabolites / Q000494:pharmacology; D023241:Antiretroviral Therapy, Highly Active; D002908:Chronic Disease; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D006679:HIV Seropositivity; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009705:Nucleosides / Q000494:pharmacology; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D012307:Risk Factors
D019380:Anti-HIV Agents; D000963:Antimetabolites; D017320:HIV Protease Inhibitors; D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors