Abstract | BACKGROUND:
Combination antiretroviral therapy suppresses but does not eradicate human immunodeficiency virus type 1 (HIV-1) in infected persons, and low-level viremia can be detected despite years of suppressive antiretroviral therapy. Short-course (28-day) intensification of standard antiretroviral combination therapy is a useful approach to determine whether complete rounds of HIV-1 replication in rapidly cycling cells contribute to persistent viremia. We investigated whether intensification with the integrase inhibitor raltegravir decreases plasma HIV-1 RNA levels in patients receiving suppressive antiretroviral therapy. METHODS: Subjects (n = 10) with long-term HIV-1 suppression receiving combination antiretroviral regimens had their regimens intensified for 4 weeks with raltegravir. Plasma HIV-1 RNA level was determined before, during, and after the 4-week intensification period, using a sensitive assay (limit of detection, 0.2 copies of HIV-1 RNA/mL of plasma). A 4-week intensification course was chosen to investigate potential HIV-1 replication in cells with relatively short (approximately 1-14-day) half-lives. RESULTS: There was no evidence in any subject of a decline in HIV-1 RNA level during the period of raltegravir intensification or of rebound after discontinuation. Median levels of HIV-1 RNA before (0.17 log10 copies/mL), during (0.04 log10 copies/mL), and after (0.04 log10 copies/mL) raltegravir intensification were not significantly different (P > .1 for all comparisons in parametric analyses). High-performance liquid chromatography and mass spectroscopy experiments confirmed that therapeutic levels of raltegravir were achieved in plasma during intensification. CONCLUSIONS: Intensification of antiretroviral therapy with a potent HIV-1 integrase inhibitor did not decrease persistent viremia in subjects receiving suppressive regimens, indicating that rapidly cycling cells infected with HIV-1 were not present. Eradication of HIV-1 from infected persons will require new therapeutic approaches. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00618371.
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Authors | D McMahon, J Jones, A Wiegand, S J Gange, M Kearney, S Palmer, S McNulty, J A Metcalf, E Acosta, C Rehm, J M Coffin, J W Mellors, F Maldarelli |
Journal | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
(Clin Infect Dis)
Vol. 50
Issue 6
Pg. 912-9
(Mar 15 2010)
ISSN: 1537-6591 [Electronic] United States |
PMID | 20156060
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-HIV Agents
- Pyrrolidinones
- RNA, Viral
- Raltegravir Potassium
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Topics |
- Adult
- Aged
- Anti-HIV Agents
(administration & dosage)
- Antiretroviral Therapy, Highly Active
(methods)
- Female
- HIV Infections
(drug therapy, virology)
- HIV-1
(isolation & purification)
- Humans
- Male
- Middle Aged
- Pyrrolidinones
(administration & dosage)
- RNA, Viral
(blood)
- Raltegravir Potassium
- Viral Load
- Viremia
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