Reservoirs of Human Immunodeficiency Virus Type 1: The Main Obstacles to Viral Eradication

Abstract

Highly active antiretroviral therapy (HAART) has led to profound decreases in morbidity and mortality rates in human immunodeficiency virus type 1 (HIV-1)-infected persons, at least in the developed world. Many infected persons have plasma levels of HIV-1 RNA that are less than the limits of detection of most clinical assays as a result of combination antiretroviral therapy. Nonetheless, HIV-1 has not been eradicated by HAART. This has been shown to be because of latent HIV-1 replication-competent provirus in resting CD4+ T lymphocytes, cryptic viral replication below the limits of detection of most clinical assays, and, possibly, the presence of viral sanctuary sites. An understanding of these reservoirs for HIV-1 in the setting of virally suppressive HAART will be critical for the development of new approaches to induce HIV-1 remissions and for the exploration of the possibility of viral eradication in the future.

Dynamics of Viral and Proviral Loads of FelineImmunodeficiency Virus within the Feline Central Nervous System duringthe Acute Phase following IntravenousInfection

“…Studies of asymptomatic HIV-1-infected patients who die some years after seroconversion either show exceptionally low proviral loads within brain tissue, consistent with levels expected from the presence of blood vessel viral loads, or may show evidence of true low-grade infections (3,5). With the increasing sensitivity of virus detection methods, it has been suggested that viral loads become dramatically reduced or regionalized and that the CNS functions as a reservoir for latent infection during the asymptomatic phase of infection (6,18,59). This obviously has major implications in the design of therapies to prevent or modify lentiviral CNS infections, since it would suggest that the acute stages of infection may be the most significant period in viral infection of the brain.…”

“…The lentivirus infections of macaques and domestic cats are excellent models for HIV infection of humans (28,47), with early infection of the brain documented in both animal groups (7,8,16,58). The dissection of the early virus-host interactions in such models may assist the development of therapies to modulate lentivirally induced CNS infection and help to investigate to what extent CNS tissue harbors reservoirs of latently infected cells, which are an important challenge when formulating lentiviral therapeutic strategies (6,59). While FIV viral and proviral loads within peripheral blood have been determined by several PCR-based methods (10,41,43,44,54,58,62), viral loads within FIV-, simian immunodeficiency virus (SIV)-, or HIV-infected brains have been determined by visual quantification of infected cells using in situ hybridization or immunocytochemical techniques (2,7,8) and to a limited extent by PCR technologies (18,58).…”

Comparison of Transcriptional Profiles Between CD4+ and CD8+ T Cells in HIV Type 1-Infected Patients

“…23 We hypothesized that finding the difference in mutual DEGs between CD4 + and CD8 + T cells at different stages of infection would provide further insight into the mechanisms and explain why CD4…”

Discovering Regulated Networks During Hiv-1 Latency and Reactivation

“…Recently, highly active anti-retroviral therapy (HAART) has led to a dramatic decrease in morbidity and mortality due to HIV and, when successful, results in undetectable levels of HIV-1 RNA in blood plasma. This stage of latency represents a period of proviral integration with little to no viral replication [1]. HIV-1 persists in a small reservoir of latently infected resting memory CD4+ T cells, which shows minimal decay even in patients on HAART and can persist for the lifetime of the patient [2,3].…”