Identification of a Reservoir for HIV-1 in Patients on Highly Active Antiretroviral Therapy

Abstract

The hypothesis that quiescent CD4+ T lymphocytes carrying proviral DNA provide a reservoir for human immunodeficiency virus-type 1 (HIV-1) in patients on highly active antiretroviral therapy (HAART) was examined. In a study of 22 patients successfully treated with HAART for up to 30 months, replication-competent virus was routinely recovered from resting CD4+ T lymphocytes. The frequency of resting CD4+ T cells harboring latent HIV-1 was low, 0.2 to 16.4 per 10(6) cells, and, in cross-sectional analysis, did not decrease with increasing time on therapy. The recovered viruses generally did not show mutations associated with resistance to the relevant antiretroviral drugs. This reservoir of nonevolving latent virus in resting CD4+ T cells should be considered in deciding whether to terminate treatment in patients who respond to HAART.

Inhibition of HIV-1 replication by novel lentiviral vectors expressing transdominant Rev and HIV-1 env antisense

“…Unlike MoMLV, lentiviral vectors can effectively transduce both dividing and non-dividing cells such as resting T cells, macrophages or dendritic cells, 9,10 which may play an important role in the maintenance of HIV-1 infection. 11,12 In addition to the effect provided by the expression of an anti-HIV gene, these vectors can inhibit HIV-1 replication by sequestering the HIV-1 regulatory proteins Tat and Rev, by interfering with reverse transcription and/or by competing for packaging into HIV-1 encoded virions, facilitating the spread of the vector to unprotected cells in vivo. [13][14][15][16] Transdominant negative mutants of Rev (TdRev) are one of the best inhibitory anti-HIV genes.…”

Viral surface glycoproteins, gp120 and gp41, as potential drug targets against HIV-1: Brief overview one quarter of a century past the approval of zidovudine, the first anti-retroviral drug

“…However HAART is complicated by the continuing emergence of drug-resistant strains of HIV and toxicities associated with the anti-retroviral agents [64,65]. Furthermore, since the combination HAART regimens are unable to eradicate HIV infection, lifelong therapy is required to avoid disease progression [66,67]. Together, these factors necessitate the continual development of new inhibitors that can be used against resistant viruses.…”

Update on the laboratory diagnosis and monitoring of HIV infection

“…Do relative changes in proviral DNA levels precede changes of viral RNA levels post HAART induction? Therefore, one of the current challenges in the HIV disease management is to detect the presence of low level proviral DNA in latently-infected CD4+ lymphocytes and other reservoirs, especially because these hidden reservoirs can replenish and revive viral infection upon activation [17][18][19]. Thus, a highly reproducible and accurate assay to quantify proviral DNA would enable a more in-depth evaluation of the efficacy of antiviral therapies.…”