Acute human immunodeficiency virus (HIV) infection (AHI) can be defined as the time from HIV acquisition until seroconversion. Incident HIV infection is less well defined but comprises the time from the acquisition of HIV (acute infection) through seroconversion (early or primary HIV infection) and the following months until infection has been well established, as characterized by a stable HIV viral load (viral load set point) and evolution of antibodies with increased concentration and affinity for HIV antigens. During AHI, a viral latent pool reservoir develops, the immune system suffers irreparable damage, and the infected (often unsuspecting) host may be most contagious. It has proved very difficult to find individuals with AHI either in longitudinal cohorts of subjects at high risk for acquiring the virus or through cross-sectional screening, and the opportunity for diagnosis is generally missed during this phase. We review the technical strategies for identifying individuals with acute or incident HIV infection. We conclude that further technical advances are essential to allow more widespread detection of patients with AHI and to affect HIV treatment outcomes and transmission prevention.

Background: In the Coronavirus Efficacy (COVE) trial, estimated mRNA-1273 vaccine efficacy against coronavirus disease-19 (COVID-19) was 94%. SARS-CoV-2 antibody measurements were assessed as correlates of COVID-19 risk and as correlates of protection. Methods: Through case-cohort sampling, participants were selected for measurement of four serum antibody markers at Day 1 (first dose), Day 29 (second dose), and Day 57: IgG binding antibodies (bAbs) to Spike, bAbs to Spike receptor-binding domain (RBD), and 50% and 80% inhibitory dilution pseudovirus neutralizing antibody titers calibrated to the WHO International Standard (cID50 and cID80). Participants with no evidence of previous SARS-CoV-2 infection were included. Cox regression assessed in vaccine recipients the association of each Day 29 or 57 serologic marker with COVID-19 through 126 or 100 days of follow-up, respectively, adjusting for risk factors. Results: Day 57 Spike IgG, RBD IgG, cID50, and cID80 neutralization levels were each inversely correlated with risk of COVID-19: hazard ratios 0.66 (95% CI 0.50, 0.88; p=0.005); 0.57 (0.40, 0.82; p=0.002); 0.41 (0.26, 0.65; p<0.001); 0.35 (0.20, 0.60; p<0.001) per 10-fold increase in marker level, respectively, multiplicity adjusted P-values 0.003-0.010. Results were similar for Day 29 markers (multiplicity adjusted P-values <0.001-0.003). For vaccine recipients with Day 57 reciprocal cID50 neutralization titers that were undetectable (<2.42), 100, or 1000, respectively, cumulative incidence of COVID-19 through 100 days post Day 57 was 0.030 (0.010, 0.093), 0.0056 (0.0039, 0.0080), and 0.0023 (0.0013, 0.0036). For vaccine recipients at these titer levels, respectively, vaccine efficacy was 50.8% (-51.2, 83.0%), 90.7% (86.7, 93.6%), and 96.1% (94.0, 97.8%). Causal mediation analysis estimated that the proportion of vaccine efficacy mediated through Day 29 cID50 titer was 68.5% (58.5, 78.4%). Conclusions: Binding and neutralizing antibodies correlated with COVID-19 risk and vaccine efficacy and likely have utility in predicting mRNA-1273 vaccine efficacy against COVID-19. Trial registration number: COVE ClinicalTrials.gov number, NCT04470427

Enhancement of HIV-specific immunity is likely required to eliminate latent HIV infection. Here, we have developed an immunotherapeutic modality aimed to improve T cell-mediated clearance of HIV-1-infected cells. Specifically, we employed Dual-Affinity Re-Targeting (DART) proteins, which are bispecific, antibody-based molecules that can bind 2 distinct cell-surface molecules simultaneously. We designed DARTs with a monovalent HIV-1 envelope-binding (Env-binding) arm that was derived from broadly binding, antibody-dependent cellular cytotoxicity-mediating antibodies known to bind to HIV-infected target cells coupled to a monovalent CD3 binding arm designed to engage cytolytic effector T cells (referred to as HIVxCD3 DARTs). Thus, these DARTs redirected polyclonal T cells to specifically engage with and kill Env-expressing cells, including CD4+ T cells infected with different HIV-1 subtypes, thereby obviating the requirement for HIV-specific immunity. Using lymphocytes from patients on suppressive antiretroviral therapy (ART), we demonstrated that DARTs mediate CD8+ T cell clearance of CD4+ T cells that are superinfected with the HIV-1 strain JR-CSF or infected with autologous reservoir viruses isolated from HIV-infected-patient resting CD4+ T cells. Moreover, DARTs mediated CD8+ T cell clearance of HIV from resting CD4+ T cell cultures following induction of latent virus expression. Combined with HIV latency reversing agents, HIVxCD3 DARTs have the potential to be effective immunotherapeutic agents to clear latent HIV-1 reservoirs in HIV-infected individuals.

Antiretroviral agents (ART) have the potential to prevent HIV transmission by reducing the concentration of HIV in blood and genital secretions. Indeed, mathematical models with favorable assumptions suggest the potential of ART to stop the spread of HIV. Empirical results from ecological and population based studies, and several short term observational studies involving HIV discordant heterosexual couples suggest that ART reduces HIV transmission. A multinational randomized controlled trial (NIH NPTN052) also examining the reliability and durability of ART as prevention in HIV discordant couples is underway. The latter and other studies also consider sexual risk taking behavior, and transmission of HIV resistant variants when ART is used as prevention. Early HIV detection and treatment (“test and treat”) are being considered as an important prevention strategy. In this article, we review the data supporting the use of ART to prevent HIV transmission, and critically examine the public health implications of this strategy.

Objective To compare patient retention at three stages of pre-antiretroviral (ART) care and two stages of post-ART care to identify when greatest attrition occurs. Design An observational cohort study. Methods We reviewed files of all adult, non-pregnant individuals testing HIV-positive January 1 – June 30, 2010, at a primary health clinic in Johannesburg, South Africa (N=842). We classified retention in pre-ART stage 1 (HIV diagnosis to CD4 results notification in ≤3 months), pre-ART stage 2 (initially ineligible for ART with repeat CD4 test ≤1 year of prior CD4), pre-ART stage 3 (initiating ART ≤3 months after first eligible CD4 result), as well as at 0–6 and 6–12 months post-ART. Results Retention among all patients during pre-ART stage 1 was 69.8% (95%CI 66.7–72.9%). For patients initially ART-ineligible (n=221), 57.4% (95%CI 49.5–65.0%) returned for a repeat CD4 during pre-ART stage 2. Among those ART-eligible (n=589), 73.5% (95%CI 69.0–77.6%) were retained during pre-ART stage 3. Retention increased with time on ART, from 80.2% (95%CI 75.3–84.5%) at 6 months to 95.3% (95%CI 91.7–97.6%) between 6–12 months. Cumulative retention from diagnosis to 12 months on ART was 36.9% (95%CI 33.0–41.1%) for those ART-eligible and 43.0% (95%CI 36.4–49.8%) from diagnosis to repeat CD4 testing within one year among those ART-ineligible. Conclusions Patient attrition in the first year following HIV diagnosis was greatest prior to ART initiation: over 25% at each of three pre-ART stages. As countries expand HIV testing and ART programs, success will depend on linkage to care, especially prior to ART eligibility and initiation.