Mo H, Lu L, King M, Louie M, Markowitz M, Rooney J, Dusak B, Brun S, Richards B, Leonard J, Kempf D, Ho D, Sun E, Molla A; Conference on Retroviruses and Opportunistic Infections.
9th Conf Retrovir Oppor Infect Feb 24 28 2002 Wash State Conv Trade Cent Seattle Wash Conf Retrovir Oppor Infect 9th 2002 Seattle Wash. 2002 Feb 24-28; 9: abstract no. 488-M.
Abbott Labs., Abbott Park, IL
BACKGROUND: The persistence of latently infected CD4+ cells represents a major barrier to virus eradication in patients on combination antiviral therapy. The half-life for decay of this latent pool of infected CD4+ T cells was estimated to be approximately 6 months in one study and 44 months in another. In this study, we examined whether a new 4-drug combination might be more potent than common combination regimens in leading to a faster decay of the latent pool of infected cells.METHODS: PBMC samples were collected at baseline and every 3 months during therapy from 8 patients whose plasma viremia levels were suppressed to undetectable levels for at least 9 months while treated with lopinavir/ritonavir, efavirenz, tenofovir DF, and lamivudine. HIV unspliced (US) mRNA and proviral DNA were quantified using a sensitive real-time PCR assay (5-30 copies/reaction).RESULTS: A substantial reduction in cell-associated US mRNA was observed in all 8 subjects. After 3 months of therapy, the median concentration of HIV US mRNA dropped sharply from 3.6 log copies/10(6) PBMC at baseline to 2.1 log copies/10(6) PBMC. At month 6 and thereafter, all subjects except one had undetectable US mRNA. The decline in cell-associated US mRNA occurred concordantly with the reduction of plasma HIV RNA. Similarly, the median concentration of proviral DNA dropped from 4.2 log copies/10(6) PBMC at baseline to 3.7 and 3.4 log copies/10(6) PBMC at months 3 and 9, respectively. The rate of decline of US mRNA in this study appears to be faster than that observed previously with standard HAART (average decrease of 1.3 log copies/10(6) PBMC after 16 months of treatment with less than 0.4 log copies/10(6) PBMC decline in the first 10 months), although the decline rate of proviral DNA was similar to that previously observed. Conclusion: Initial results from this pilot study of a novel 4-drug antiretroviral regimen suggest that it may be possible to reduce the pool of latently infected CD4+ cells to a greater degree over a shorter period of time than that reported for other HAART treatment regimens.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Antiretroviral Therapy, Highly Active
- CD4-Positive T-Lymphocytes
- DNA
- DNA, Viral
- HIV Infections
- HIV Seropositivity
- Humans
- Lamivudine
- RNA, Messenger
- Ritonavir
- Viremia
Other ID:
UI: 102264073
From Meeting Abstracts