Thirty Years with HIV Infection〞Nonprogression Is Still Puzzling: Lessons to Be Learned from Controllers and Long-Term Nonprogressors

作者：Julie C Gaardbo; Hans J Hartling; Jan Gerstoft; Susanne D Nielsen

来源：AIDS Research and Treatment, 2012, 2012: 1-14.

DOI：10.1155/2012/161584

In the early days of the HIV epidemic, it was observed that a minority of the infected patients did not progress to AIDS or death and maintained stable CD4+ cell counts. As the technique for measuring viral load became available it was evident that some of these nonprogressors in addition to preserved CD4+ cell counts had very low or even undetectable viral replication. They were therefore termed controllers, while those with viral replication were termed long-term nonprogressors (LTNPs). Genetics and virology play a role in nonprogression, but does not provide a full explanation. Therefore, host differences in the immunological response have been proposed. Moreover, the immunological response can be divided into an immune homeostasis resistant to HIV and an immune response leading to viral control. Thus, non-progression in LTNP and controllers may be due to different immunological mechanisms. Understanding the lack of disease progression and the different interactions between HIV and the immune system could ideally teach us how to develop a functional cure for HIV infection. Here we review immunological features of controllers and LTNP, highlighting differences and clinical implications. 1. Introduction Prior to the introduction of combination antiretroviral therapy (cART) it was observed that a minority of the individuals infected with Human Immunodeficiency Virus type 1 (HIV-1, from now on referred to as HIV) did not progress to Acquired Immunodeficiency Syndrome (AIDS) or death. This minority maintained normal CD4+ cell counts in the absence of treatment for several years〞in some cases for more than two decades (reviewed in [1]) and therefore the terminology Long-Term Nonprogressors (LTNP) was proposed. When the technique for measuring the viral load was introduced it became evident that some of these patients, who did not clinically progress, had low or even nondetectable viral replication. This phenomenon leads to the additive definition of the non progressor-phenotype referred to as controllers due to their ability to control viral replication in the absence of cART. Today, non-progressors are a collective name for controllers and LTNP who are clinically similar. Except for certain demands for the duration of the infection in LTNP, they are only to be differentiated according to control or not of viral replication, respectively. Understanding the mechanism for the lack of disease progression in controllers and LNTP could ideally teach us how to develop a functional cure for HIV infection, and for this reason these subpopulations of HIV-infected