ABSTRACT
OBJECTIVES: Antigen-induced activation and proliferation of HIV-1-infected cells is hypothesized to be a mechanism of HIV persistence during antiretroviral therapy. The objective of this study was to determine if proliferation of H1N1-specific HIV-infected cells could be detected following H1N1 vaccination. METHODS: This study utilized cryopreserved PBMC from a previously conducted trial of H1N1 vaccination in HIV-infected pregnant women. HIV-1 DNA concentrations and 437 HIV-1 C2V5 env DNA sequences were analyzed from ten pregnant women on effective antiretroviral therapy, before and 21 days after H1N1 influenza vaccination. RESULTS: HIV-1 DNA concentration did not change after vaccination (median pre- vs. post-vaccination: 95.77 vs. 41.28 copies/million PBMC, p = .37). Analyses of sequences did not detect evidence of HIV replication or proliferation of infected cells. CONCLUSIONS: Antigenic stimulation during effective ART did not have a detectable effect on the genetic makeup of the HIV-1 DNA reservoir. Longitudinal comparison of the amount and integration sites of HIV-1 in antigen-specific cells to chronic infections (such as herpesviruses) may be needed to definitively evaluate whether antigenic stimulation induces proliferation of HIV-1 infected cells.
Subject(s)
HIV Infections/immunology , HIV-1/isolation & purification , Influenza A Virus, H1N1 Subtype/immunology , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Pregnancy Complications, Infectious/immunology , Anti-HIV Agents/therapeutic use , Antigens, Viral , Antiretroviral Therapy, Highly Active/methods , Base Sequence , CD4 Lymphocyte Count , Female , HIV Infections/blood , HIV Infections/drug therapy , HIV-1/genetics , HIV-1/growth & development , Humans , Influenza Vaccines/administration & dosage , Influenza, Human/drug therapy , Influenza, Human/immunology , Leukocytes, Mononuclear , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/virology , Proviruses/isolation & purification , Sequence Analysis , Treatment Outcome , Virus ReplicationABSTRACT
Antiretroviral treatment (ART) of HIV infection suppresses viral replication. Yet if ART is stopped, virus reemerges because of the persistence of infected cells. We evaluated the contribution of infected-cell proliferation and sites of proviral integration to HIV persistence. A total of 534 HIV integration sites (IS) and 63 adjacent HIV env sequences were derived from three study participants over 11.3 to 12.7 years of ART. Each participant had identical viral sequences integrated at the same position in multiple cells, demonstrating infected-cell proliferation. Integrations were overrepresented in genes associated with cancer and favored in 12 genes across multiple participants. Over time on ART, a greater proportion of persisting proviruses were in proliferating cells. HIV integration into specific genes may promote proliferation of HIV-infected cells, slowing viral decay during ART.
