Long-term Nonprogressive Disease Among Untreated HIV-Infected Individuals

Abstract

As of 2008, more than 33 million adults and children have been estimated to be living with human immunodeficiency virus (HIV). Among them are rare patients (<0.5%) who have remained clinically well without antiretroviral therapy after almost 20 years of infection. They maintain stable CD4 cell counts and suppressed HIV replication to levels comparable with those measured in patients receiving combination antiretroviral therapy. No known epidemiologic or behavioral factors are predictive of untreated, nonprogressive HIV infection; however, host genetics and immune response factors, most specifically HLA antigen class I-restricted HIV-specific CD8 T cells, appear to be primarily responsible for this remarkable phenotype in a majority of these individuals. These patients offer hope that durable control of HIV infection is possible and can provide important insight to inform the development of the next generation of HIV/AIDS vaccines and immune-based therapies. This article reviews clinical features of these unique patients and discusses them in the context of nonprogressors enrolled in other cohorts. Potential mechanisms underlying nonprogressive HIV infection and scientific discoveries, facilitated by the participation of these patients in clinical trials, of relevance to the design of an efficacious HIV/AIDS vaccine are also highlighted.

Elite Controllers and Long-term Nonprogressors: Models for HIV Vaccine Development?

“…However, this combined phenotype likely represents the most advantageous approach for vaccine development research in these groups since this combined phenotype has a greater number of desirable characteristics than the singular elite controller and LTNP phenotypes. Due to the stability and durability inherent in a combined definition, this combination elite controller/LTNP phenotype has also been proposed in the literature [50]. In particular, the trait of spontaneous virologic control demonstrated in elite controllers is of lesser value if HIV disease progression occurs despite a suppressed viral load.…”

CD8 + T Cell Breadth and Ex Vivo Virus Inhibition Capacity Distinguish between Viremic Controllers with and without Protective HLA Class I Alleles

“…Understanding the mechanisms of natural viral control in HIV infection is crucial for the identification of correlates of immune protection and for the design of an effective HIV vaccine. Previous studies have linked HIV control to a number of immunological factors, particularly HIVspecific CD8 ϩ cytotoxic T lymphocytes (CTLs), which have been demonstrated to play an important role (2)(3)(4)(5). However, virusspecific CD8 ϩ T cell immune responses are not equally effective in HIV control, as the majority of infected individuals progress to disease despite the presence of these cells.…”

Comparison of clinical and laboratory profile of Haart adherent and non-adherent HIV/AIDS patients in Calabar, Nigeria

“…Optimal adherence leads to suppression of viral replication, thus reducing likelihood for HIV mutations that could lead to drug resistant viral strains. Also, optimal adherence prevents further destruction of the cellular immune system with consequent increase in the level of CD4 cells and reduction in development of opportunistic infections (Migueles and Connors, 2010).…”