Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection

• Published in: PloS one 2010-02, Vol.5 (2), p.e9390-e9390
• Main Authors: Archin, Nancie M, Cheema, Manzoor, Parker, Daniel, Wiegand, Ann, Bosch, Ronald J, Coffin, John M, Eron, Joseph, Cohen, Myron, Margolis, David M
• Format: Article
• Language: English
• Subjects: Acids; Acquired immune deficiency syndrome; AIDS; Amplification; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Antiretroviral Therapy, Highly Active; CD4 antigen; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes - virology; Controlled release; Depletion; Drug Administration Schedule; Drug resistance; Drug therapy; Drug Therapy, Combination; Enfuvirtide; Enzyme Inhibitors - therapeutic use; Health aspects; Highly active antiretroviral therapy; Histone deacetylase; Histone Deacetylase Inhibitors - therapeutic use; HIV; HIV Envelope Protein gp41 - therapeutic use; HIV Infections - blood; HIV Infections - drug therapy; HIV tests; HIV-1 - drug effects; HIV-1 - genetics; Human immunodeficiency virus; Humans; Infection; Infections; Infectious Diseases/HIV Infection and AIDS; Infectious Diseases/Viral Infections; Latency; Level (quantity); Lymphocytes T; Male; Males; Pathogenesis; Patient compliance; Patients; Peptide Fragments - therapeutic use; Prospective Studies; Pyrrolidinones - therapeutic use; Raltegravir Potassium; Ribonucleic acid; RNA; RNA, Viral - blood; T cells; Therapy; Treatment Outcome; Valproic acid; Valproic Acid - therapeutic use; Viremia; Viremia - prevention & control; Virology/Persistence and Latency; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0009390

Human immunodeficiency virus (HIV) infection that persists despite antiretroviral therapy (ART) is a daunting problem. Given the limited evidence that resting CD4+ T cell infection (RCI) is affected by the histone deacetylase (HDAC) inhibitor valproic acid (VPA), we measured the stability of RCI and residual viremia in patients who added VPA with or without raltegravir (RAL), or enfuvirtide (ENF) with or without VPA, to standard ART. Patients with plasma HIV RNA50%) was seen in six volunteers after the addition of RAL and VPA. In 4 of the 6 patients this lack of effect might be attributed to intermittent viremia, low VPA levels, or intermittent study therapy adherence. Overall, there was no effect of the addition of RAL or ENF on low-level viremia measured by SCA. The prospective addition of VPA and RAL, VPA and ENF, or ENF failed to progressively reduce the frequency of RCI, or ablate intermittent and low-level viremia. New approaches such as more potent HDAC inhibition, alone or in combination with intensified ART or other agents that may disrupt proviral latency must be pursued.