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Intrahost viral sequence diversity can be evaluated over multiple genomic regions using next-generation sequencing (NGS) and scaled to population-level diversity to identify recent human immunodeficiency virus type 1 infection. Using Primer-ID NGS, we sequenced the reverse transcriptase (RT) and env V1-V3 regions from persons with known infection dates, and assessed the mean (π) and first quintile of pairwise diversity distributions over time. The receiver operating characteristic area under the curve (AUC) of RT and V1-V3 combined showed excellent discrimination of recent infection <9 months: using π (only single transmitted variants: AUC, 0.98; threshold <1.03%; sensitivity, 97%; specificity, 89%) and the first quintile (including all variants: AUC, 0.90; threshold <0.60%; sensitivity, 91%; specificity, 92%).

Objective Estimate association between postpartum antiretroviral adherence and breastmilk HIV-1 transmission Design Prospective cohort study Methods Mother-infant pairs were randomized after delivery to immediately begin receiving 28 weeks of either triple maternal antiretrovirals (zidovudine, lamivudine, and either nevirapine, nelfinavir, or lopinavir-ritonavir) or daily infant nevirapine as part of the Breastfeeding, Antiretrovirals, and Nutrition study. Associations between postpartum antiretroviral adherence and rate of breastmilk HIV-1 transmission were estimated using Cox models. We measured adherence over four postpartum time intervals using pill count, suspension bottle weight, and maternal self-report. Adherence was categorized and lagged by one interval. Missing adherence measures were multiply imputed. Infant HIV-1 infection was determined by DNA PCR every 2-6 weeks. The primary endpoint was infant HIV-1 infection by 38 weeks of age among infants alive and uninfected at 5 weeks. Results Analyses included 1479 mother-infant pairs and 45 transmission events. Using pill count and bottle weight information, 22-40% of mother-infant pairs at any given interval were <90% adherent. Having ≥90% adherence was associated with a 52% (95% CI 3-76%) relative reduction in the rate of breastmilk HIV-1 transmission, compared with having <90% adherence when controlling for study arm, breastfeeding status, and maternal characteristics. Complete case analysis rendered similar results (n=501; relative reduction 59%, 95% CI 6-82%). Conclusion Non-adherence to extended postpartum ART regimens in ‘real world’ settings is likely to be higher than that seen in BAN. Identifying mothers with difficulty adhering to antiretrovirals, and developing effective adherence interventions, will help maximize benefits of ARV provision throughout breastfeeding.

Purpose of Review Acute and early HIV (AHI) is a pivotal time during HIV infection, yet there remain major shortfalls in diagnosis, linkage to care, and antiretroviral therapy (ART) initiation during AHI. We introduce an AHI-specific cascade, review recent evidence pertaining to the unique challenges of AHI, and discuss strategies for improving individual and public health outcomes. Recent Findings Presentation during AHI is common. Expanding use of 4th generation testing and pooled nucleic acid amplification testing (NAT) has led to improved AHI detection in resource-wealthy settings. Technologies capable of AHI diagnosis are rare in resource-limited settings; further development of point-of-care devices and utilization of targeted screening is needed. Rapid ART initiation during AHI limits reservoir seeding, preserves immunity, and prevents transmission. Reporting of AHI cascade outcomes is limited, but new evidence suggests that impressive rates of diagnosis, linkage to care, rapid ART initiation, and viral suppression can be achieved. Summary With advancements in AHI diagnostics and strong evidence for the therapeutic and prevention benefits of ART initiated during AHI, improving AHI cascade outcomes is both crucial and feasible. HIV guidelines should recommend diagnostic algorithms capable of detecting AHI and prescribe rapid, universal ART initiation during AHI.

Background/Aims Retaining patients in prevention of mother-to-child transmission of HIV studies can be challenging in resource limited settings, where high lost to follow-up (LTFU) rates have been reported. In this paper, we describe the effectiveness of methods used to encourage retention in the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study and analyze factors associated with LTFU in the study. Methods The BAN clinical trial was designed to evaluate the efficacy of 3 different mother-to-child HIV transmission prevention strategies. Lower than expected participant retention prompted enhanced efforts to reduce LTFU during the conduct of the trial. Following study completion, we employed regression modeling to determine predictors of perfect attendance and variables associated with being LTFU. Results During the study, intensive tracing efforts were initiated after the first 1686 mother-infant pairs had been enrolled, and 327 pairs were missing. Sixty of these pairs were located and had complete data obtained. Among the 683 participants enrolling after initiation of intensive tracing efforts, the LTFU rate was 3.4%. At study's end, 290 (12.2%) of the 2369 mother-infant pairs were LTFU. Among successfully traced missing pairs, relocation was common and three were deceased. Log-binomial regression modeling revealed higher maternal hemoglobin and older maternal age to be significant predictors of perfect attendance. These factors and the presence of food insecurity were also significantly associated with lower rates of LTFU. Conclusions In this large HIV prevention trial, intensive tracing efforts centered on reaching study participants at their homes succeeded in finding a substantial proportion of LTFU participants, and were very effective in preventing further LTFU during the remainder of the trial. The association between food insecurity and lower rates of LTFU is likely related to the study's provision of nutritional support, including a family maize supplement, which may have contributed to patient retention.

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