Prospective Study of Acute HIV-1 Infection in Adults in East Africa and Thailand

Abstract

Background Acute human immunodeficiency virus type 1 (HIV-1) infection is a major contributor to transmission of HIV-1. An understanding of acute HIV-1 infection may be important in the development of treatment strategies to eradicate HIV-1 or achieve a functional cure. Methods We performed twice-weekly qualitative plasma HIV-1 RNA nucleic acid testing in 2276 volunteers who were at high risk for HIV-1 infection. For participants in whom acute HIV-1 infection was detected, clinical observations, quantitative measurements of plasma HIV-1 RNA levels (to assess viremia) and HIV antibodies, and results of immunophenotyping of lymphocytes were obtained twice weekly. Results Fifty of 112 volunteers with acute HIV-1 infection had two or more blood samples collected before HIV-1 antibodies were detected. The median peak viremia (6.7 log10 copies per milliliter) occurred 13 days after the first sample showed reactivity on nucleic acid testing. Reactivity on an enzyme immunoassay occurred at a median of 14 days. The nadir of viremia (4.3 log10 copies per milliliter) occurred at a median of 31 days and was nearly equivalent to the viral-load set point, the steady-state viremia that persists durably after resolution of acute viremia (median plasma HIV-1 RNA level, 4.4 log10 copies per milliliter). The peak viremia and downslope were correlated with the viral-load set point. Clinical manifestations of acute HIV-1 infection were most common just before and at the time of peak viremia. A median of one symptom of acute HIV-1 infection was recorded at a median of two study visits, and a median of one sign of acute HIV-1 infection was recorded at a median of three visits. Conclusions The viral-load set point occurred at a median of 31 days after the first detection of plasma viremia and correlated with peak viremia. Few symptoms and signs were observed during acute HIV-1 infection, and they were most common before peak viremia. (Funded by the Department of Defense and the National Institute of Allergy and Infectious Diseases.)

Envelope residue 375 substitutions in simian–human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques

“…In each case, we were successful in constructing SHIVs that replicated well in RMs with plasma viral load kinetics (Fig. 5) remarkably similar to acute and early chronic HIV-1 infection in humans (72,73). In other recent studies, we created a seventh SHIV, this one from a T/F HIV-1 subtype C virus Ce1176 (74), that is part of a widely used 12-member global neutralization panel developed by Montefiori, Seaman, and coworkers (71).…”

Very early antiretroviral therapy permits CD8 T cells to keep HIV reservoirs at bay

“…As the peak of viremia predicts viral set point, indicating that very early events are at play before CD8 T cells kick in (23). Innate immune response that occurs within hours induces production of type I interferons (IFNs), which regulate many immune pathways including the function of CD8 T cells.…”

Computational analysis of antibody dynamics identifies recent HIV-1 infection

“…The analysis includes the presence or absence of the response along with the magnitude and avidity of the antibody response when present. We evaluated plasma from 70 recent and 66 longstanding HIV-1 infections ("training panel") of multiple subtypes (A, AE, B, C) from the Center for HIV/AIDS Vaccine Immunology (CHAVI) 001 cohort (27), the US Military HIV Research Program (USMHRP) RV217 cohort (28), and the Consortium for the Development and Performance of HIV Incidence Assays (CEPHIA) repository (29), including specimens from 39 patients on antiretroviral therapy (Table 1). A recency cutoff of 9 months (270 days) was used to train the model for this analysis based upon initial characterization of candidate biomarkers using samples from the CEPHIA repository and CHAVI 001 acute infection cohorts (data not shown).…”

“…Sources included HIV-1 acute and chronic cohorts from CHAVI (CHAVI 001, CHAVI 008) (27,37), the US Military HIV Research Program (RV217) (28), and from the specimen repository created and maintained by CEPHIA, which has been previously described (6,12). EDSC was determined as described previously (6).…”