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.

HIV antibody screening remains indispensable for ensuring viral safety of blood components despite NAT implementation

“…HIV infection status had been ascertained by two positive results with an ELISA and a confirmed HIV-1 + Western blot assay. In this cohort of HIV + donors, we focused on subjects subsequently recognized as long-term nonprogressors (defined as individuals belonging to CDC A stage and maintaining a stable CD4 + T-cell count despite at least a decade of seropositivity 13,14 ). Subjects presenting, on several consecutive samples, a viral load lower than 400 copies per mL (as determined in a previous study 13 ) in the absence of any therapy for HIV infection were selected for the study.…”

“…In this cohort of HIV + donors, we focused on subjects subsequently recognized as long-term nonprogressors (defined as individuals belonging to CDC A stage and maintaining a stable CD4 + T-cell count despite at least a decade of seropositivity 13,14 ). Subjects presenting, on several consecutive samples, a viral load lower than 400 copies per mL (as determined in a previous study 13 ) in the absence of any therapy for HIV infection were selected for the study. HIV viral loads were tested once more with a licensed HIV test (Amplicor HIV-1 Monitor test, Version 1.5 [ultrasensitive], Roche Diagnostics Systems, Branchburg, NJ) with an unfrozen aliquot.…”

Immune activation and antibody responses in non‐progressing elite controller individuals infected with HIV‐1

“…Since the early 1990s, cohort studies have identified a small percentage ($5-10%) of HIV-1-infected people, called long-term non-progressors, who remain asymptomatic and maintain a relative high CD4 þ T-cell count (>500 cells/ml) for >8-10 years without antiviral therapy [Buchbinder and Vittinghoff, 1999]. Despite the absence of clinical symptoms for many years, most of those individuals display many hallmarks of HIV-1 infection including: low but persistent viral replication [Lefrere et al, 1997;Barker et al, 1998;Rodes et al, 2004], rapidly evolving viral quasispecies [Wolinsky et al, 1996;Delwart et al, 1997;Shioda et al, 1997], and evidence of chronic immune activation [Lifson et al, 1991;Sheppard et al, 1993;Ferbas et al, 1995;Lefrere et al, 1997;Barker et al, 1998;Zaunders et al, 1999]. After prolonged infection, many long-term non-progressors had evidence of immunologic damage and suffered a transition from the non-progressor to the progressor state, suggesting that most of them are actually slow progressors rather than true non-progressor patients [Lefrere et al, 1997;Learmont et al, 1999;Rodes et al, 2004].…”

Comparison of the Biological Basis for Non-HIV Transmission to HIV-Exposed Seronegative Individuals, Disease Non-Progression in HIV Long-Term Non-Progressors and Elite Controllers

“…With the introduction of virologic testing, it was discovered that most LTNPs had low to moderate levels of viremia. Subsequent follow-up studies revealed that many LTNPs experienced progressively increasing viral loads and declining CD4+ T-cell counts [ 16 , 17 , 18 , 19 ]. The recognition of LTNPs’ ability to resist disease progression and remain free of symptoms for prolonged periods occurred approximately ten years into the HIV-1 pandemic.…”