HIV DNA is a marker of HIV persistence that predicts HIV progression and remission, but its kinetics in early acute HIV infection (AHI) is poorly understood. We longitudinally measured the frequency of peripheral blood mononuclear cells harboring total and integrated HIV DNA in 19 untreated and 71 treated AHI participants, for whom 50 were in the earliest Fiebig I/II (HIV IgM-) stage, that is ≤2weeks from infection. Without antiretroviral therapy (ART), HIV DNA peaked at 2weeks after enrollment, reaching a set-point 2weeks later with little change thereafter. There was a marked divergence of HIV DNA values between the untreated and treated groups that occurred within the first 2weeks of ART and increased with time. ART reduced total HIV DNA levels by 20-fold after 2weeks and 316-fold after 3years. Therefore, very early ART offers the opportunity to significantly reduce the frequency of cells harboring HIV DNA.

Loss of gut mucosal integrity and an aberrant gut microbiota are proposed mechanisms contributing to chronic inflammation and increased morbidity and mortality during antiretroviral-treated HIV disease. Sexual practice has recently been uncovered as a major source of microbiota variation, potentially confounding prior observations of gut microbiota alterations among persons with HIV (PWH). To overcome this and other confounding factors, we examine a well-powered subset of AGEhIV Cohort participants comprising antiretroviral-treated PWH and seronegative controls matched for age, body-mass index, sex, and sexual practice. We report significant gut microbiota differences in PWH regardless of sex and sexual practice including Gammaproteobacteria enrichment, Lachnospiraceae and Ruminococcaceae depletion, and decreased alpha diversity. Men who have sex with men (MSM) exhibit a distinct microbiota signature characterized by Prevotella enrichment and increased alpha diversity, which is linked with receptive anal intercourse in both males and females. Finally, the HIV-associated microbiota signature correlates with inflammatory markers including suPAR, nadir CD4 count, and prevalence of age-associated noncommunicable comorbidities.

Purpose of review The long-lived viral reservoir is a major obstacle to achieving a cure for HIV. Therapeutic strategies, such as early antiretroviral therapy (ART), may be a prerequisite to achieving long-term control of viral replication upon ART withdrawal. Recent findings HIV persistence is established early in acute HIV infection (AHI) with infection in long-lived memory CD4⁺ T cells. Studies conducted in nonhuman primates have suggested that this could occur as early as 3 days postinfection; however, the timing in humans is uncertain. ART during AHI significantly restricts the HIV reservoirs as compared with later treatment. Early ART, particularly prior to the detection of HIV immunoglobulin M, may also reduce the contribution of the long-lived central memory CD4⁺ T cells to the total HIV reservoir, a profile observed in individuals who naturally control HIV without ART. Summary It is clear that early ART has a greater impact in limiting the HIV reservoirs than later treatment. However, latently infected long-lived memory CD4⁺ T cells persist in most early treated individuals. Therefore, additional interventions will likely be required to eliminate all cells capable of producing replication-competent virus but treatment in AHI may be the critical first step in containing the HIV reservoirs.

Background: We previously reported similar AIDS-free survival at 3 years in children who were >1 year old initiating antiretroviral therapy (ART) and randomized to early versus deferred ART in the Pediatric Randomized to Early versus Deferred Initiation in Cambodia and Thailand (PREDICT) study. We now report neurodevelopmental outcomes. Methods: Two hundred eighty-four HIV-infected Thai and Cambodian children aged 1–12 years with CD4 counts between 15% and 24% and no AIDS-defining illness were randomized to initiate ART at enrollment (“early,” n = 139) or when CD4 count became <15% or a Centers for Disease Control (CDC) category C event developed (“deferred,” n = 145). All underwent age-appropriate neurodevelopment testing including Beery Visual Motor Integration, Purdue Pegboard, Color Trails and Child Behavioral Checklist. Thai children (n = 170) also completed Wechsler Intelligence Scale (intelligence quotient) and Stanford Binet Memory test. We compared week 144 measures by randomized group and to HIV-uninfected children (n = 319). Results: At week 144, the median age was 9 years and 69 (48%) of the deferred arm children had initiated ART. The early arm had a higher CD4 (33% versus 24%, P < 0.001) and a greater percentage of children with viral suppression (91% versus 40%, P < 0.001). Neurodevelopmental scores did not differ by arm, and there were no differences in changes between arms across repeated assessments in time-varying multivariate models. HIV-infected children performed worse than uninfected children on intelligence quotient, Beery Visual Motor Integration, Binet memory and Child Behavioral Checklist. Conclusions: In HIV-infected children surviving beyond 1 year of age without ART, neurodevelopmental outcomes were similar with ART initiation at CD4 15%–24% versus <15%, but both groups performed worse than HIV-uninfected children. The window of opportunity for a positive effect of ART initiation on neurodevelopment may remain in infancy.

Objective: Understanding the extent to which early antiretroviral therapy (ART) can limit the establishment and persistence of the HIV reservoir is an important step to designing interventions aimed at achieving HIV cure. We measured the markers of HIV persistence and HIV-specific immunity in early treated children. Design: This is a cross-sectional study that enrolled 15 children older than 2 years of age who initiated ART before 6 months of age and had sustained viral suppression. Total and integrated HIV DNA, and 2-LTR circles in CD4⁺ T cells, HIV antibody response by fourth generation HIV enzyme immunoassay, and CD4⁺ and CD8⁺ T-cell responses to gag/env peptides by intracellular cytokine staining of CD4⁺ and CD8⁺ T cells were measured. Results: The median current age was 6.3 years and age at ART initiation was 17 weeks. The median duration of viral suppression was 6 years, and all had HIV RNA less than 50 copies/ml. The median CD4⁺ T cells was 44%. The median total HIV DNA was 132 copies/10⁶ CD4⁺ T cells (range 11–1804) and integrated HIV DNA was 17 copies/10⁶ CD4⁺ T cells (range 0–516), and no one had detectable 2-LTR circles. Nine of the 15 children (60%) had undetectable or extremely low integrated HIV DNA (<20 copies/10⁶ CD4⁺ T cells). All except one (93%) had undetectable HIV-specific CD4⁺/CD8⁺ cell responses and seven (47%) had nonreactive enzyme immunoassay. Conclusion: Early ART resulted in very low levels of markers of HIV persistence and undetectable HIV-specific immune responses in the majority of HIV-infected children who started ART before 6 months of age.