Zhang L, Ramratnam B, Tenner-Racz K, He Y, Vesanen M, Lewin S, Hurley A, Racz P, Perelson AS, Korber BT, Markowitz M, Ho DD; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 6th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 6th 1999 Chic Ill. 1999 Jan 31-Feb 4; 6th: 160 (abstract no. 495).
Aaron Diamond AIDS Research Center, The Rockefeller University, New York.
To study the effectiveness of combination antiretroviral therapy and the decay characteristics of lantently infected cells, we undertook a study in 8 highly selected patients whose plasma viremia had been undetectable for 2-3 years after commencing antiretroviral therapy (AZT/3TC plus 1 or 2 protease inhibitors). Proviral DNA sequences from patients' PBMC were analyzed and the sequence evolution was used as evidence for residual HIV-1 replication. In 6 cases, exclusive of hypermutated forms, there was no significant proviral sequence variation during the treatment period. However, sequence evolution indicative of ongoing HIV-1 replication was found in 2 patients, in the absence of drug-resistant viral genotypes. Extensive in situ studies performed on one of the latter cases not only provided additional evidence for persistent viral replication, but also localized the productively infected cells to the lymph node, tonsil and colon. These findings suggest that in some cases, treatment intensification may be necessary to achieve complete suppression of HIV-1 replication. Two independent approaches were also taken to estimate the decay rate of replication-competent HIV-1 harbored latently within resting memory CD4 lymphocytes. One was based on the decay in parental proviral sequences identified at the primary infection, and the other was a direct measurement of the latent reservoir using a limiting-dilution boosted culture technique. Both approaches yielded a decay half-life of approximately 6 months (7-10), suggesting that the elimination of this latent reservoir will require many years of effective antiretroviral treatment.
Publication Types:
Keywords:
- CD4-Positive T-Lymphocytes
- HIV-1
- Humans
- Lamivudine
- Zidovudine
Other ID:
UI: 102195264
From Meeting Abstracts