Cavert W, Staskus K, Zupancic M, Wietgrefe S, Notermans D, Danner S, Henry K, Mills R, Haase AT; 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: 207 (abstract no. LB9).
University of Minnesota, Minneapolis, MN.
We employed computerized quantitative image analysis coupled with ISH (AT Haase, et al, Science, 274:985, 1996) to evaluate serial uni-or bilateral tonsil biopsies from ten previously antiretroviral-naive, HIV-1 seropositive adults (median absolute CD4+ count=194/mm(3)) treated for six months with ritonavir, zidovudine and lamivudine. Participants constituted a LT substudy of open-label protocol NUCB 2019. The man pretreatment follicular dendritic cell (FDC) associated HIV-1 RNA load was 1.5x10(8) copies/gram, while the mean frequency of actively productive(greater than or equal to 20 RNA copies/cell) monoculear cells (MNCs)/gram was 2.3x10(5) cells/gram LT. Subsequent biopsies were measured at 2, 22 and 180 days on therapy. We observed an initial quicker-than-expected turnover in the FDC-associated pool along with a rapid initial decrease in the MNC frequency. After 6 months of therapy, the mean change in the FDC-associated virus pool was greater than or equal to - 3.8 log(10), while the MNC frequency decreased greater than or equal to 2.2 log(10). At 180 days a heterogeneous residuum of HIV-1 RNA was detectable in most patients, with some showing HIV-1 RNA in the RDC pool while others showed persistent low-copy-number/cell CD4+ MNCs. At 6 months, one patient had no HIV-1 RNA detectable by exhaustive ISH (estimated MNC lower detection limit of less than 300 cells/gram for cells with greater than 1 copy/cell) or by a sensitive nested RT-PCR LT homogenization assay. However, LT from all ten subjects had residual proviral DNA detected at six months. This cohort remains under active investigation. Conclusions: By quantitative ISH, six months of triple combination therapy (a protease inhibitor and two NRET inhibitors) reduces HIV-1 viral load by orders of magnitude in both major LT cellular compartments. Between individuals the viral RNA residue varies as to the dominant cellular reservoir. In one subject LT RNA was undetectable, but proviral DNA persisted in all.
Publication Types:
Keywords:
- Adult
- Humans
- In Situ Hybridization
- Lamivudine
- Lymphoid Tissue
- Lymphotoxin-alpha
- Male
- RNA, Viral
- Ritonavir
- Zidovudine
- drug therapy
Other ID:
UI: 102223030
From Meeting Abstracts