The Challenge of Finding a Cure for HIV Infection

Abstract

Although combination therapy for HIV infection represents a triumph for modern medicine, chronic suppressive therapy is required to contain persistent infection in reservoirs such as latently infected CD4+ lymphocytes and cells of the macrophage-monocyte lineage. Despite its success, chronic suppressive therapy is limited by its cost, the requirement of lifelong adherence, and the unknown effects of long-term treatment. This review discusses our current understanding of suppressive antiretroviral therapy, the latent viral reservoir, and the needs for and challenges of attacking this reservoir to achieve a cure.

Viral epigenomes in human tumorigenesis

“…Several models have been proposed to explain proviral silencing (Mok and Lever, 2007;Han et al, 2008;Duverger et al, 2009;Richman et al, 2009). Although DNA methylation of the HIV 5 0 -LTR is known to suppress viral gene expression (Bednarik et al, 1990), more complex processes have been discovered that govern this transcriptional feature.…”

“…Recent studies have shed more light on these complex silencing mechanisms (Duverger et al, 2009;Richman et al, 2009). A new mechanism regulating viral gene expression has emerged, explaining the lack of associations between the gene silencing and histone modifications or DNA methylation found in many cases.…”

“…Finally, the role of endogenous miRNAs that may impede provirus transcription or translation (Richman et al, 2009) is worth noting, although more research is needed to determine the complex genetic and epigenetic mechanisms by which this virus may finally induce cancer.…”

The good and evil of complement activation in HIV-1 infection

“…These formidable scientific challenges may be related to the high genetic variability of the virus, the lack of immune correlates of protection, limitations of the existing animal models and logistical problems associated with the conduction of multiple clinical trials. [97][98][99] Thus, a safe, globally effective, and affordable HIV-1 vaccine still seems far away.…”

Single-Molecule Threshold of HIV Fate Decision

“…HAART treatment allows patients to suppress the disease to levels that are below the standard detection limit. Yet, whereas these patients show no symptoms or detectable viral load, they carry latent viruses at <1 in 10^6 CD4þ T-cells (5). A lapse in HAART treatment can cause resurgence of the disease and, therefore, the costly therapy must continue for the lifetime of the patient, a challenge in developing countries.…”