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Transmitted HIV Drug Resistance Persists & May Reduce Response to HAART
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"Evolution of resistance mutations acquired at time of primary infection: persistence in circulating and archived HIV strains"
Note from Jules Levin: as previous studies have also reported, this study reports the risk accompanying transmission of drug resistant HIV. The resistance can persist and may reduce response to HAART. Similar risks have been reported associated with superinfection, which is when a person already infected with HIV may get infected with a second virus from another HIV-infected person. This second virus may have drug resistance and may be more virulent. Studies suggest superinfection with a second virus may accelerate HIV progression.
ABSTRACT 48
Antiviral Therapy 2004; 9:S57.
J Ghosn1, I Pellegrin2, C Deveau3, J Galimand1, M Harzic4, C Tamalet5, JP Viard1, C Goujard6, L Meyer3, C Rouzioux1 and ML Chaix1
1 CHU Necker-Enfants Malades, EA MRT 3620, Paris; 2 CHU Pellegrin, Bordeaux; 3 Inserm U569, Le Kremlin-Bicêtre, France; 4 CH Le Chesnay, Versailles; 5 CHU La Timone, Marseille; and 6 CHU Bicêtre, Le Kremlin-Bicêtre, France
BACKGROUND: The recently reported transmission and persistence of drug-resistant HIV is a matter of concern for public policy.
OBJECTIVES: To analyse the evolution of resistance mutations acquired at primary HIV infection (PHI) in plasma and PBMC compartments.
METHODS: Ten patients (five treated) included in the French ANRS Primo cohort and harbouring HIV strains resistant to at least one antiretroviral drug at PHI, underwent longitudinal monitoring of viral loads and resistance genotype (bulk sequencing) in plasma and in PBMC [median follow-up 24 months (12--48)].
RESULTS: Baseline median plasma HIV-RNA and PBMC-HIV DNA loads were 4.3 log10 copies/ml (1.7--5.7) and 2.9 log10 copies/106 cells (1.8--3.7), respectively. For each patient, baseline genotypic resistance profile was identical in plasma HIV RNA and PBMC HIV DNA.
Of the five untreated patients (A to E), three, one and one, respectively, were identified with resistance to one (A:41L/210W/215C; B:41L/215Y; C:103N), two (D:41L/215Y/84V/90M) and three (E:41L/103N/210W/215Y/90M) antiretroviral classes. All resistance-associated mutations persisted in plasma and in PBMC throughout the follow-up (median M24), except for mutation 215Y that reverted to 215C in both plasma HIV RNA and PBMC HIV DNA at M12in patient B, and M24 in patient D and E.
Of the five patients receiving triple antiretroviral combination (F to J), one, two and two, respectively, were identified with resistance to one (F:46I), two (G:67N/69N/184V/215F/84V;H:41L/184V/215Y/84V) and three (I:67N/69N/70R/103N/151M/184V/215V/46I/82A;J:67N/69D/70R/181C/215F/54V/82A/90M) antiretroviral classes. Patients I and J achieved undetectable plasma HIV RNA at M6, with retention of archived drug-resistance mutations in PBMC HIV DNA for up to a median of 24-month follow-up.
Conversely, in the other three patients, decrease in plasma HIV RNA was slower, thus promoting the accumulation of additional drug-resistance mutations in plasma HIV RNA as soon as M6 in two of them (addition of 70R/101E/190S in patient G and 184V in patient F).
CONCLUSIONS: HIV-resistant variants acquired at time of PHI may establish themselves as the dominant viral population, and are archived in the latent cellular reservoir. The absence of genotypic changes in circulating and archived viruses in a drug-free environment further supports the concept of expansion of a monoclonal resistant population. In such patients, classicaltriple-combination may be sub-optimal, thus promoting the accumulation of drug-resistance mutations and jeopardizing the already limited therapeutic options.
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