Rapid development of HIV elite control in a patient with acute infection

Abstract

Background Elite controllers (EC), a small subset of the HIV-positive population (< 1%), suppress HIV viremia below the limit of quantification of clinical viral load assays in the absence of antiretroviral therapy (ART). However, there is a paucity of longitudinal data detailing the viral and immune dynamics or HIV reservoir seeding during acute infection in individuals that go on to become Elite Controllers. Case presentation In this report, we describe a case of a 42 year old woman diagnosed during acute infection who rapidly and permanently suppressed her viremia in the absence of antiretroviral therapy (ART). Rapid antibody/antigen testing was either negative or equivocal during acute infection, despite subsequent viral load testing at that time point with 71,550 plasma HIV RNA copies/mL, making initial diagnosis challenging. The patient subsequently developed detectable anti-HIV antibodies and an increase in HIV-specific CD8+ T cell responses to overlapping subtype C HIV gag peptide; very low-level plasma viremia (0.84 RNA copies/mL) was detected by an ultrasensitive assay 2 years following infection. Subsequently, she was started on ART for multifocal furunculosis despite continued suppression of virus and stable CD4+ T cell counts. Following ART initiation, CD8+ T cell responses increased, but no HIV DNA or RNA was able to be isolated from large numbers of peripheral blood CD4+ T cells. Conclusion This case provides important information regarding the establishment of elite HIV control during acute infection and also demonstrates an increase in HIV-specific immune responses following ART despite undetectable peripheral blood cellular measures of HIV persistence. This case also highlights the challenges in diagnosing acute HIV infection without the use of viral load testing in this rare elite controller phenotype.

HIV proviral burden, genetic diversity, and dynamics in viremic controllers who subsequently initiated suppressive antiretroviral therapy

“…To do the former, we modified an existing mathematical model that assumes that, during untreated infection, HIV sequences enter the proviral pool at a rate proportional to their abundance in plasma, after which they are cleared at a constant rate (see methods and (23)). While the original approach modeled pre-ART viral load dynamics using typical parameterization appropriate for non-controllers (23), we used a piecewise linear function that merged each participant’s pVL data with acute phase dynamics drawn from the (limited) literature on HIV controllers (37–39) (see methods and Table S1 ). Figures 8A-D show the participants’ viral load histories incorporating these acute-phase dynamics, while Figures 8E-H show their proviral age distributions on ART, depicted as the proportion of distinct proviruses that dated to each year prior to ART (or, in the case of participant 3, to each year prior to their viremic episode after ART), as blue bars.…”

“…To recreate each participant’s in vivo plasma viral dynamics as realistically as possible, we merged each participant’s available pVL data to acute phase dynamics observed in viremic controllers (37) (because peak viremia was not captured in our participants’ measured viral load data). We also performed sensitivity analyses using peak viremia kinetics observed in elite controllers (38, 39). The acute-phase dynamics we used are shown in Table S1 .…”

Long-Term SARS-CoV-2-Specific Immune and Inflammatory Responses Across a Clinically Diverse Cohort of Individuals Recovering from COVID-19

“…We implemented an in-house ICS assay as previously described with minor modifications to be consistent with other published SARS-CoV-2-specific assays (Henrich et al 2017; Scully et al 2018; Morley et al 2019). Briefly, cells were rested overnight before stimulation.…”

Viral reservoirs in elite controllers of HIV-1 infection: Implications for HIV cure strategies

“…The high percentage of CD4+ T cells with clonally expanded provirus and/or with provirus integrated in intergenic sites or sites with heterochromation features is probably a consequence of elite control rather than a cause. There have been very few studies of ECs during primary infection, but it appears that many of these patients never develop the high levels of viremia that is often seen in CPs and control viral replication shortly after infection [ 19 , [67] , [68] , [69] ]. The mechanism of control is unclear but may be due to rapid expansion of HIV-specific CD8+ T cells.…”