Clinical Outcomes of Elite Controllers, Viremic Controllers, and Long‐Term Nonprogressors in the US Department of Defense HIV Natural History Study

Abstract

Durable control of human immunodeficiency virus (HIV) replication and lack of disease progression in the absence of antiretroviral therapy were studied in a military cohort of 4586 subjects. We examined groups of elite controllers (ie, subjects with plasma HIV RNA levels of <50 copies/mL; prevalence, 0.55% [95% confidence interval {CI}, 0.35%-0.80%]), viremic controllers (ie, subjects with plasma HIV RNA levels of 50-2000 copies/mL; prevalence, 3.34% [95% CI, 2.83%-3.91%]), and subjects with a lack of disease progression (ie, long-term nonprogressors [LTNPs]) through 7 years of follow-up (LTNP7s; prevalence, 3.32% [95% CI, 2.70%-4.01%]) or 10 years of follow-up (LTNP10s; prevalence, 2.04% [95% CI, 1.52%-2.68%]). For elite and viremic controllers, spontaneous virologic control was established early and was typically observed when the initial viral load measurement was obtained within 1 year of estimated seroconversion. Elite controllers had favorable time to development of AIDS (P=.048), a CD4 cell count of 350 cells/microL (P= .009), and more-stable CD4 cell trends, compared with viremic controllers. LTNPs defined by 10-year versus 7-year criteria had a longer survival time (P=.001), even after adjustment for differing periods of invulnerability (P= .042). Definitions of controllers and LTNPs describe distinct populations whose differing clinical outcomes improve with the stringency of criteria, underscoring the need for comparability between study populations.

Post-treatment control of HIV infection

“…Our model offers a number of testable predictions: (i) There is a range of typical effector cell responses where PTC cannot be attained, no matter how small the viral reservoir. This regime describes most patients, because PTCs comprise 5-15% of the population (1) and elite controllers comprise <1% of the population (11,12). (ii) For individuals with responses in this regime, boosting their immune responses before termination of treatment may enhance the probability of post-treatment control.…”

“…1 do not appear to be ECs because they typically lacked protective HLA class I alleles-specifically, HLA-B*27 and B*57-that are generally overrepresented in ECs, as well as the strong HIV-specific immune responses found in most ECs (10). Further, ECs form only a fraction of a percent of the population (11,12), far less than the 5-15% of study patients found to be PTCs (1,2).…”

Correlating cellular and molecular signatures of mucosal immunity that distinguish HIV controllers from noncontrollers

“…1 These HIV controllers represent less than 5% of infected persons and are defined by their ability to maintain circulating virus loads at undetectable or very low levels. 2 Usually, but not always, controllers are also long-term nonprogressors, as defined by their ability to maintain normal CD4 ϩ T-cell counts and to remain clinically healthy for more than 10 years. 3,4 At the opposite end of the spectrum, HIV-infected noncontrollers have sustained high viral loads (Ͼ 10 000 copies/ mL) and usually experience disease progression, as defined by the loss of circulating CD4 ϩ T cells and the development of AIDS.…”

Immunovirological parameters and cytokines in HIV infection

“…A minority of individuals infected by HIV, denominated long term non-progressors (LTNP) remain healthy for more than 10 years without clinical evidence of disease progression 6,7 in the absence of combined antiretroviral therapy (cART). These cases, represented by approximately 5% to 15% of those infected 8 are characterized by stability or increase in CD4+ T count and strong response of cytotoxic T lymphocytes (CTL) against HIV, different to what occurs in TyP 9 .…”