Tivecommons.org/ publicdomain/zero/1.0/) applies to the data made available in
Tivecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Weber et al. AIDS Res Ther (2017) 14:Page 2 ofBackground Infection with human immunodeficiency virus type 1 (HIV-1)–in the absence of antiretroviral therapy– usually follows a well-defined path of virological and immunological ONO-4059 biological activity changes; however, progression rates to advanced AIDS vary significantly among infected individuals [1, 2]. Based on plasma HIV-1 RNA (viral) load, CD4+ T-cell counts, and symptomatic or asymptomatic HIV-1 infection adult patients have been classified into four groups: (i) rapid progressors (RP), (ii) typical progressors (TP), and two groups of long-term non-progressors (LTNP) namely (iii) elite controllers and (iv) viremic controllers [3, 4]. Among the latter, a rare subgroup of HIV-1-infected individuals has been described who do not seem to progress to AIDS, maintaining high CD4+ T-cell counts despite high levels of viremia (i.e., over 2000 HIV-1 copies RNA/ml of plasma) for many years, also called viremic non-progressors (VNPs) [5?]. Multiple studies have tried to associate these differences in HIV-1 disease progression with PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28300835 a multitude of host (HIV-1-specific immune response and genetic markers) and viral factors [9?3]. Among the immunological factors, strong HIV-1-specific cytotoxic T cell (CTL) responses have been shown to control HIV-1 infection right after transmission, perhaps determining viral set point in chronic stages of infection, which may help reduce the rate of HIV-1 disease progression [14, 15]. Similarly, a series of host genetic factors that seem to influence HIV-1 progression rates have been well described, including human leukocyte antigen (HLA) class I alleles such as HLA-B*27 and HLA-B*57 [16, 17] and a 32 bp deletion in the CCR5 chemokine receptor gene [18?2]. On the other hand, the impact of restriction cellular factors like APOBEC3, TRIM5, tetherin, and SAMHD1 on HIV-1 progression is still debated [10, 23]. Altogether, it has been long recognized that immune activation is one of the major contributors to HIV-1 disease and pathogenesis [6, 24?7]. Viral factors–such as impaired HIV-1 replicative fitness–have been associated with slow or limited HIV-1 disease progression [11, 28?1], particularly in patients infected with heavily mutated drug resistant viruses [28, 30, 32?5]. High fitness of transmitted HIV-1 has been related to rapid disease progression [36], while some individuals carrying viruses with decreased replication capacity during acute/early infection have been classified as HIV controllers [37]. Although isolating replication competent HIV-1 strains from elite controllers has been difficult, two studies failed to identify any major defect on the replication ability of these viruses [38, 39]. In contrast, recombinant viruses constructed with HIV-1 gag, pol, and/or env genes from elite controllers exhibited reduced replication capacity compared to recombinantviruses constructed from typical progressors [40?2]. On the other hand, very limited information about the replicative fitness of viruses infecting viremic non-progressor individuals is PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/29069523 currently available [6, 43]. If a decrease in HIV-1 replicative fitness is associated with slower/no disease progression, what is causing the virus to have this reduced replication capacity–in the absence of drug resistance mutations–in a certain number of non-progressor patients? To date, no common pattern or polymorphism.