Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppi J, Taylor H, Chadwick K, Margolick J, Zeiger M, Barditch-Crovo P, Siliciano RF; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 4th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 4th 1997 Wash DC. 1997 Jan 22-26; 4th: 135 (abstract no. 383).
Johns Hopkins University, Baltimore, MD.
Advances in anti-retroviral therapy have raised the possibility that in some individuals HIV-1 infection might be eradicated. Combinations of anti-retroviral agents can reduce circulating free virus to undetectable levels in some individuals. However, latently infected cells carrying integrated or unintegrated provirus provide a reservoir in which the virus can persist in the presence of these drugs. We have therefore analyzed the total body load of latently infected cells using novel molecular and cellular assays. Our results indicate that the fraction of latently infected CD4+ T cells carrying integrated HIV-1 DNA is extremely low (less than 0.01%), is not different in blood and lymph nodes, and remains at a stable steady state with declining CD4 counts. An average of 25% of the integrated provirus is replication-competent. The dominant form of provirus, present in 200 fold higher copy number than integrated HIV-1 DNA, is a full length, unintegrated species that is not blunt ended. Total body loads of resting and activated CD4+ T cells with integrated provirus were 6.7 x 10(6) and 1.2 x 10(7) cells, respectively. Virus load in lymph node and alveolar macrophages was also determined. The frequency of lymph node macrophages with integrated provirus was less than 0.1%, with even lower frequencies in macrophages in the lung. These results indicate that HIV-1 infection persists and progresses even though only minute fractions of the susceptible cell populations are stably infected. The surprisingly small size of the latent reservoir offers hope for virus eradication and immune reconstitution.
Publication Types:
Keywords:
- Anti-HIV Agents
- Anti-Retroviral Agents
- Antigens, CD4
- CD4 Lymphocyte Count
- HIV Infections
- HIV Protease Inhibitors
- HIV-1
- Lymph Nodes
- Proviruses
- immunology
Other ID:
UI: 102223277
From Meeting Abstracts