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HIV-1 resistant strains acquired at the time of primary infection massively fuel the cellular reservoir and persist for lengthy periods of time.
AIDS. 2006 Jan 09; 20(2):159-70.AIDS

Abstract

OBJECTIVE

Characterization of the early establishment of the viral reservoir in patients acquiring resistant strains at primary HIV-1 infection (PHI), and longitudinal analysis of resistance mutations in circulating virions and intracellular HIV strains.

PATIENTS AND METHODS

Drug-resistance was compared between HIV RNA and peripheral blood mononuclear cell (PBMC)-HIV DNA at the time of PHI in 44 patients enrolled in the Primo Cohort and harbouring plasma HIV-1 resistant to at least one antiretroviral drug. Longitudinal monitoring of viral load and resistance genotype was performed in plasma-HIV RNA and PBMC HIV DNA for at least 24 months in a subset of 10 patients. Phylogenetic analysis of HIV DNA protease gene clones was used to explore the diversity of quasi-species at baseline.

RESULTS

Baseline resistance profile was identical in paired HIV RNA and PBMC HIV DNA for all 44 patients. All resistance-associated mutations persisted in plasma and PBMC over 2 years in the five untreated patients. Of the five patients started on empirical HAART, two achieved undetectable HIV RNA at month 6, with long-term persistence of archived drug-resistance mutations in PBMC HIV DNA. Virological failure was observed in the other three patients, resulting in the accumulation of additional drug-resistance mutations in HIV RNA and HIV DNA for two of them. Phylogenetic analysis of HIV DNA clones showed highly homogenous and exclusively resistant quasi-species in the cellular reservoir at baseline.

CONCLUSION

HIV resistant strains acquired at the time of PHI massively fuel the cellular reservoir, and their prolonged persistence is supported by the early expansion of a dominant homogenous and resistant viral population. Results in treated patients showed that classical empirical triple-combination may be suboptimal.

Authors+Show Affiliations

Laboratoire de Virologie, CHU Necker Enfants Malades, Université René Descartes Paris, France. jade.ghosn@psl.ap-hop-paris.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16511408

Citation

Ghosn, Jade, et al. "HIV-1 Resistant Strains Acquired at the Time of Primary Infection Massively Fuel the Cellular Reservoir and Persist for Lengthy Periods of Time." AIDS (London, England), vol. 20, no. 2, 2006, pp. 159-70.
Ghosn J, Pellegrin I, Goujard C, et al. HIV-1 resistant strains acquired at the time of primary infection massively fuel the cellular reservoir and persist for lengthy periods of time. AIDS. 2006;20(2):159-70.
Ghosn, J., Pellegrin, I., Goujard, C., Deveau, C., Viard, J. P., Galimand, J., Harzic, M., Tamalet, C., Meyer, L., Rouzioux, C., & Chaix, M. L. (2006). HIV-1 resistant strains acquired at the time of primary infection massively fuel the cellular reservoir and persist for lengthy periods of time. AIDS (London, England), 20(2), 159-70.
Ghosn J, et al. HIV-1 Resistant Strains Acquired at the Time of Primary Infection Massively Fuel the Cellular Reservoir and Persist for Lengthy Periods of Time. AIDS. 2006 Jan 9;20(2):159-70. PubMed PMID: 16511408.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HIV-1 resistant strains acquired at the time of primary infection massively fuel the cellular reservoir and persist for lengthy periods of time. AU - Ghosn,Jade, AU - Pellegrin,Isabelle, AU - Goujard,Cécile, AU - Deveau,Christiane, AU - Viard,Jean-Paul, AU - Galimand,Julie, AU - Harzic,Martine, AU - Tamalet,Catherine, AU - Meyer,Laurence, AU - Rouzioux,Christine, AU - Chaix,Marie-Laure, AU - ,, PY - 2006/3/3/pubmed PY - 2006/12/9/medline PY - 2006/3/3/entrez SP - 159 EP - 70 JF - AIDS (London, England) JO - AIDS VL - 20 IS - 2 N2 - OBJECTIVE: Characterization of the early establishment of the viral reservoir in patients acquiring resistant strains at primary HIV-1 infection (PHI), and longitudinal analysis of resistance mutations in circulating virions and intracellular HIV strains. PATIENTS AND METHODS: Drug-resistance was compared between HIV RNA and peripheral blood mononuclear cell (PBMC)-HIV DNA at the time of PHI in 44 patients enrolled in the Primo Cohort and harbouring plasma HIV-1 resistant to at least one antiretroviral drug. Longitudinal monitoring of viral load and resistance genotype was performed in plasma-HIV RNA and PBMC HIV DNA for at least 24 months in a subset of 10 patients. Phylogenetic analysis of HIV DNA protease gene clones was used to explore the diversity of quasi-species at baseline. RESULTS: Baseline resistance profile was identical in paired HIV RNA and PBMC HIV DNA for all 44 patients. All resistance-associated mutations persisted in plasma and PBMC over 2 years in the five untreated patients. Of the five patients started on empirical HAART, two achieved undetectable HIV RNA at month 6, with long-term persistence of archived drug-resistance mutations in PBMC HIV DNA. Virological failure was observed in the other three patients, resulting in the accumulation of additional drug-resistance mutations in HIV RNA and HIV DNA for two of them. Phylogenetic analysis of HIV DNA clones showed highly homogenous and exclusively resistant quasi-species in the cellular reservoir at baseline. CONCLUSION: HIV resistant strains acquired at the time of PHI massively fuel the cellular reservoir, and their prolonged persistence is supported by the early expansion of a dominant homogenous and resistant viral population. Results in treated patients showed that classical empirical triple-combination may be suboptimal. SN - 0269-9370 UR - https://www.unboundmedicine.com/medline/citation/16511408/HIV_1_resistant_strains_acquired_at_the_time_of_primary_infection_massively_fuel_the_cellular_reservoir_and_persist_for_lengthy_periods_of_time_ L2 - https://doi.org/10.1097/01.aids.0000199820.47703.a0 DB - PRIME DP - Unbound Medicine ER -