Cellular proviral HIV-DNA decline and viral isolation in naïve subjects with <5000 copies/ml of HIV-RNA and >500 x 10(6)/l CD4 cells treated with highly active antiretroviral therapy

AIDS. 2000 Jan 7;14(1):23-9. doi: 10.1097/00002030-200001070-00003.

Abstract

Objective: To evaluate the decay rate of cellular proviral HIV-DNA and viral replication in patients receiving highly active antiretroviral therapy (HAART) in the very early phase of infection.

Methods: Thirty-four patients treated with HAART and retrospectively selected for progressive decline of plasma viraemia up to undetectable levels (< 20 copies/ml), were stratified according to CD4+ cell count and plasma viraemia at base line: > 500 x 10(6) cells/l with < 5000 copies/ml (group 1) or with > 5000 copies/ml (group 2), > 5000 copies/ml with 300-500 x 10(6) cells/l (group 3) or with < 300 x 10(6) cells/l (group 4). Plasma HIV-RNA and proviral HIV-DNA were analysed at baseline and after 1, 2, 3, 6, 9 and 12 months of treatment.

Results: After 1 year of treatment, a significant decrease of proviral DNA titre was observed in all patients and a decrease > 1 log was achieved in 24 of 29 subjects of the first three groups. The more pronounced decay of HIV-DNA (half-life 28 weeks) up to < 50 HIV-DNA copies/10(6) CD4+ cells was detected in patients of group 1. At the year's endpoint, five patients (four in group 1 and one in group 2) had < 20 HIV-DNA copies. However, HIV strains sensitive to antiretroviral drugs were isolated from peripheral lymphocytes of 16 out of 34 patients.

Conclusion: In patients with undetectable plasma viraemia after 1 year of HAART, the highest reduction of proviral DNA up to < 50 copies/10(6) CD4+ cells was obtained only in subjects in the early asymptomatic phase of infection. Nevertheless, a replication-competent virus can be detected in all phases of antiretroviral therapy.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • DNA, Viral / blood*
  • Didanosine / therapeutic use
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / growth & development*
  • HIV-1 / metabolism
  • Humans
  • Indinavir / therapeutic use
  • Male
  • Middle Aged
  • Prospective Studies
  • Proviruses / growth & development*
  • Proviruses / metabolism
  • RNA, Viral / blood*
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stavudine / therapeutic use
  • Viremia / drug therapy*

Substances

  • Anti-HIV Agents
  • DNA, Viral
  • HIV Protease Inhibitors
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Indinavir
  • Stavudine
  • Didanosine