Reservoirs of HIV Replication After Successful Combined Antiretroviral Treatment

Abstract

Sustained reduction of viral replication can be achieved in HIV infected patients after treatment with combinations of drugs (HAART) that inhibit the viral reverse transcriptase, and protease enzymes. However, replication competent virus can still be recovered from latently infected resting memory CD4+ T-cell lymphocytes. Moreover, "covert" virus replication has been demonstrated in patients who experienced reductions in plasma viremia to levels below the limit of detection of the most sensitive PCR assays. In most studies, preferential attention has been given to latent resting CD4+ T-lymphocytes as a source of HIV persistence. However, insufficient suppression of HIV replication could also lead to viral re-emergence after HAART interruption. In addition to CD4+ T- lymphocytes, other host cells such as long-lived resident macrophages or recently infected blood monocytes could also contribute to maintain persistent HIV replication after HAART. Establishing the origin of re-emerging HIV in patients under HAART upon treatment interruption is important to design optimal treatment schemes. Therapeutic strategies aimed at reducing the number of latently infected cells involve immune activation with IL-2, or other stimulatory factors, in the presence of antiretroviral drugs. Elimination of replication-competent virus would require intensification of HAART, or the use of antiretroviral drugs achieving an effective concentration at the site of HIV replication. In this review the mechanisms of HIV persistence and the methods that can be used to distinguish latent from covert HIV replication in different cell types will be discussed.

Short Communication: Human Blood Dendritic Cells Are Infected Separately from Monocytes in HIV Type 1 Patients

“…Human immunodeficiency virus-1 (HIV-1) interacts with monocytes via CD4 and chemokine receptors, 1 but alternative receptors such as fibronectin 2 and membrane glycolipids 3 can contribute to the binding process. Even though treatment with highly active antiretroviral therapy (HAART) can result in sustained periods of undetectable viral loads, replication-competent HIV-1 can still be isolated from peripheral blood monocytes, [4][5][6] however, most likely not from their most common form, CD14 þ monocytes. 7 HIV-1 can readily be isolated from differentiated cells.…”

Administration of Fludarabine-Loaded Autologous Red Blood Cells in Simian Immunodeficiency Virus-Infected Sooty Mangabeys Depletes pSTAT-1-Expressing Macrophages and Delays the Rebound of Viremia after Suspension of Antiretroviral Therapy

“…Infected M/M persist throughout the course of disease as long-term stable reservoirs able to produce large amounts of virions and to disseminate them in other cells and tissues (6,22,24,33). As such, persistence of active viral replication in M/M despite prolonged antiretroviral treatment represents a major obstacle to HIV eradication (8,25,34) It should also be noted that currently available drugs have poor antiviral activity against the M/M compartment (1). Collectively, these considerations define the rationale for designing therapeutic approaches aimed at eliminating, or at least reducing, the levels of active HIV replication in M/M in HIV-infected patients.…”

Evaluation of the safety and pharmacokinetic profile of the broad spectrum antiviral lectin Griffithsin.

“…One complicating factor in disease management is that once HIV-1 is systemically established, viral reservoirs appear to make systemic eradication of the virus impossible [98][99][100][101]. Viral reservoirs are believed to be the latent infection of long lived memory cells.…”

“…Viral reservoirs are believed to be the latent infection of long lived memory cells. However, it is also possible that a low level viremia intermittently continues or a combination of both of those factors [98][99][100][101][102]. The practical effect of this latent infection is seen through the fact that shortly after discontinuing HAART, viral load levels rebound in the majority of patients.…”