Short-Course Raltegravir Intensification Does Not Reduce Persistent Low-Level Viremia in Patients with HIV-1 Suppression during Receipt of Combination Antiretroviral Therapy

• Published in: Clinical infectious diseases Vol. 50; no. 6; pp. 912 - 919
• Main Authors: McMahon, D., Jones, J., Wiegand, A., Gange, S. J., Kearney, M., Palmer, S., McNulty, S., Metcalf, J. A., Acosta, E., Rehm, C., Coffin, J. M., Mellors, J. W., Maldarelli, F.
• Format: Journal Article
• Language: English
• Published: Oxford The University of Chicago Press 15.03.2010; University of Chicago Press; Oxford University Press
• Subjects: Adult; Aged; Anti-HIV Agents - administration & dosage; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Antiretroviral Therapy, Highly Active - methods; Antiretrovirals; Antiviral agents; Antivirals; Biological and medical sciences; Chromatography; Drug therapy; Female; Half lives; HIV; HIV 1; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - isolation & purification; HIV/AIDS; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infections; Infectious diseases; Male; Mass spectrometry; Medical sciences; Middle Aged; Patients; Pharmacology. Drug treatments; Protease inhibitors; Pyrrolidinones - administration & dosage; Raltegravir Potassium; RNA; RNA, Viral - blood; T lymphocytes; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Viremia; Viruses; Human; Immunopathology; Antiretroviral agent; Drug combination; HIV-1 virus; Viremia; Retroviridae; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Chemotherapy; Integrase inhibitor; Treatment; Viral disease; Antiviral; Combined treatment; Human immunodeficiency virus; Raltegravir
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1086/650749

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 ( im;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 (Pµ.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.