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18th International HIV Drug Resistance WorkshopBasic Principles & Clinical ImplicationsJune 9–13 2009, Fort Myers, Florida, USA |
ANTIRETROVIRAL INTENSIFICATION DOES NOT REDUCE PERSISTENT HIV-1 VIREMIA ON THERAPY
Antivir Ther 2009; 14 Suppl 1:A12 (abstract no. 10)
J Dinoso1, J Jones2, D McMahon2, A Wiegand3, M Kearney3, J Spindler3, S Palmer3,4, S McNulty2, J Metcalf5, E Acosta6 , R Siliciano1, J Coffin3,7, J Mellors2 and F Maldarelli3
1Johns Hopkins University, Baltimore, MD, USA; 2University of Pittsburgh, Pittsburgh, PA, USA; 3HIV Drug Resistance Program, NCI, NIH, Frederick, MD, USA; 4Department of Virology, Swedish Institute for Infectious Disease Control, Karolinska Institute, Solna, Sweden; 5Laboratory of Immunoregulation, NIAID, Bethesda, MD, USA; 6University of Alabama, Birmingham, AL, USA; 7Tufts University School of Medicine, Boston, MA, USA
BACKGROUND: Combination antiretroviral therapy suppresses plasma HIV-1 RNA to <50 copies/ml for prolonged periods. Therapy is not curative, however, and persistent low-level viremia is detectable with sensitive assays. The source of residual viremia is uncertain, but production from long-lived, chronically infected cells or from ongoing, complete cycles of virus replication are likely possibilities. In order to investigate the source of persistent viremia, we conducted three drug intensification studies using NNRTI, PI and integrase inhibitor therapy.
METHODS: Participants (n=18) on combination antiretroviral therapy with NNRTI- or PI-based regimens, including 2 NRTIs and with stable HIV-1 RNA<50 copies/ ml plasma for >6 months were enrolled in intensification studies at three sites (University of Pittsburgh, Johns Hopkins and NIH), and residual viremia was determined using a sensitive HIV-1 RNA assay (single copy assay [SCA]). Thirteen participants underwent 4-week intensification with either efavirenz (n=2), lopinavir/r (n=2) or raltegravir (n=9); five participants underwent 8-week intensification with atazanavir. Plasma for HIV-1 quantification and drug level determination was obtained prior to, during and following the intensification period. A total of 257 single-copy determinations were performed. Data were analyzed using parametric statistics.
RESULTS: Enrolled patients (16 males and 2 females) had undergone combination antiretroviral therapy with suppressed viremia for 0.7–15 years. Median viral RNA levels prior to intensification were 1.7–2.7 copies/ml consistent with previous studies of low-level viremia. During intensification, median viremia ranged from 1.6 to 5.6 copies/ml. No significant decreases in viremia were noted in any of the 18 participants undergoing PI, NNRTI or raltegravir intensifications. Following intensification, HIV-1 viremia levels were 1.1–4.8 copies/ml in the three studies. CD4+ T-cell counts remained stable with no significant changes during or following intensification. Plasma drug determination studies revealed therapeutic levels of intensification agent were achieved in all patients. Drug intensification was well tolerated with no serious adverse events.
CONCLUSIONS: Intensification with antiretrovirals targeting RT, protease or integrase does not decrease the level of residual viremia. These results are inconsistent with the hypothesis that persistent viremia results from ongoing complete cycles of viral replication. New therapeutic approaches will be required to eliminate HIV-1 reservoirs. The speaker will review the state of the field and introduce the concepts to be covered by the other speakers in this session before addressing the topic that is summarized by the title below.
2009-06-09
10
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