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Decay of replication competent HIV-1 in resting CD4 T cells during prolonged antiretroviral treatment
Originally Published on September 1, 1999

B Ramratnam, L Zhang, S Bonhoeffer, A Hurley, M Stevens, DD Ho and M Markowitz.

Antiviral Therapy 1999; 4 (Supplement 1): Abstract 161

ABSTRACT:

Purpose: To determine the decay characteristics of replication-competent HIV-1 during antiretroviral treatment

Methods: Thirty-two HIV-1-infected individuals on combination antiretroviral treatment (3-4 drugs) were studies. Longitudinal quantitative microcultures of CD8 lymphocyte-depleted PBMC were performed over a 1-3 year period and the levels of replication-competent Hiv-1 were determined by the maximum likelihood method. Decay parameters including compartment half-life (t1/2) were determined by least squares linear regression. Monthly plasma HIV-1 RNA (Roche Ultra-Sensitive) measurements were performed.

Results: All patients experienced a 10-1,000-fold reduction in replication-competent HIV-1 during the first 3 months of treatment. Thereafter, levels of replication-competent HIV-1 decreased slowly in 25/32 individuals with an overall mean t1/2 of 49 weeks (range 17-194 weeks). No decay was observed in 7?32). Intermittent viraemia occurred in 17/25 with decay and 7/7 without decay. Individuals with intermittent viraemia had slower decay compared to individuals with plasma HIV-1 RNA consistently <50 copies/mL (t1/2 59 weeks versus 26 weeks, p+0.007).

Conclusion: (I) Replication competent HIV-1 in resting CD4 T cells decays with a t1/2 of approximately 6 months in individuals with HIV-1 RNA consistently <50 copies-mL. (ii) Apparently, slower decay occurs in individuals with intermittent viraemia probably due to replenishment of the pool. (iii) Intermittent viraemia is common during prolonged treatment.

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