Even Individuals Considered as Long-Term Nonprogressors Show Biological Signs of Progression After 10 Years of Human Immunodeficiency Virus Infection

Abstract

Despite a decade of human immunodeficiency virus (HIV) seropositivity, a few individuals termed as long-term nonprogressors (LTNPs) maintain a stable CD4+ T-cell count for a period of time. The aim of this study was to establish, through the sequential determination of all known predictors of HIV disease, the proportion of such patients having stringent criteria of true long-term nonprogression. Among 249 individuals who were HIV-infected and prospectively followed up over a 10-year period (1985 to 1995), 12 having a CD4+ T-cell count greater than 500/μL (LTNP I group) and 9 having a CD4+ T-cell count less than 500 but stable over time (LTNP II group) after at least 10 years of infection without intervention of antiviral therapy, were studied over the entire follow-up period. The plasma HIV RNA copy number and the serum concentrations of p24 antigen, each anti-HIV antibody, neopterin, β-2-microglobulin, Immunoglobulin (Ig) G and IgA were determined every 18 months over the study period. Cellular and plasma viremias were cross-sectionaly assayed in all 21 patients. Only two patients had strictly no marker of progression over the follow-up period. They were the only ones who had, over the 10-year period, a viral copy number too low to be detected. The other patients had a viral copy number higher than 400/mL at at least one visit and increasing over the follow-up period, and they evidenced one or more markers of virological or immunological deterioration. Cellular viremia was positive in all patients but two, while plasma viremia was negative in all but one. The population of individuals termed as LTNPs is not virologically and immunologically homogeneous. The majority present biological signs of HIV disease progression. A new pattern of true LTNP can be drawn through stringent criteria based on the whole known predictors. This pattern appears to be rare in HIV-positive population.

Primary HIV-1 infection sets the stage for important B lymphocyte dysfunctions

“…The situation of the LTNP is far from straightforward. It is reported that LTNPs do have increased activation of the immune system (Franceschi et al 1997;Rodes et al 2004) and show biological signs of disease progression after 10 years of HIV infection (Lefrere et al 1997 and African green monkeys (Broussard et al 2001;Silvestri et al 2003). It has been shown that HIV-2 is more closely related to SIV than to HIV-1 and similar to SIV, the relatively milder course of infection may be explained by a lower degree of immune activation than HIV-1.…”

Non‐progression of HIV infection 20 years after diagnosis

“…Nonprogression of HIV infection is uncommon 1 ‐4 and, to our knowledge, nonprogression for more than 20 years’ duration has not been reported previously. We believe that this person re‐presents the tail of the Gaussian distribution in the natural history of HIV infection, rather than a distinct and exceptional subgroup.…”

“…Six years ago, we described a cohort of 21 blood donors whose HIV infections, which had been detected by routine screening of their donated blood, were characterized by long‐term nonprogression. We defined an HIV long‐tern nonprogressor (LTNP) as a person whose HIV infection was at least 10 years in duration, without HIV‐linked symptoms, and whose CD4+ cell count was greater than 500 per µL without antiretroviral therapy 1 . Most persons in the cohort have received antiretroviral therapy because of disease progression (decreasing CD4+ cell counts or increasing plasma HIV RNA load).…”

Cytotoxic T Lymphocyte Responses in HIV-1-Infected Long-Term Nonprogressors: Lessons for Vaccine Design

“…In the absence of antiviral therapy, AIDS develops typically within 5-7 years after infection, although very rapid disease progression in less than 2 years or virtually no disease progression for more than 25 years are observed as well (Figure 1) 1 . Individuals with a long-term nonprogressive HIV infection (long-term nonprogressors, LTNPs), defined by us as an asymptomatic HIV-1-positive follow-up of at least 9 years with stable CD4 counts above 400 cells in the ninth year of follow-up, comprise approximately 5% of the total HIV-1-infected population [2][3][4] . While LTNPs generally still have a low but detectable viral load, more recently a group of so-called "elite controllers" has been identified 5,6 .…”

“…While LTNPs generally still have a low but detectable viral load, more recently a group of so-called "elite controllers" has been identified 5,6 . These individuals have maintained HIV RNA levels below 50 copies/ml for at least 1 year in the absence of antiretroviral therapy and constitute less than 1% of the HIV-1 infected population [4][5][6][7] Several factors have been identified that influence the rate of HIV-1 disease progression [8][9][10][11][12] . Individuals infected with attenuated viruses, for instance HIV-1 variants with a deletion in the viral nef gene 13 , showed prolonged asymptomatic survival [13][14][15] , whereas a high viral load set point, which may relate to the replication potential of the virus, is highly predictive for accelerated disease progression 16 .…”