Using Primer-ID Deep Sequencing to Detect Recent Human Immunodeficiency Virus Type 1 Infection.

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%).

Reducing lost to follow-up in a large clinical trial of prevention of mother-to-child transmission of HIV: the Breastfeeding, Antiretrovirals and Nutrition study experience.

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 rates have been reported. In this article, we describe the effectiveness of methods used to encourage retention in the Breastfeeding, Antiretrovirals, and Nutrition study and analyze factors associated with lost to follow-up in the study. METHODS: The Breastfeeding, Antiretrovirals, and Nutrition clinical trial was designed to evaluate the efficacy of three different mother-to-child HIV transmission prevention strategies. Lower than expected participant retention prompted enhanced efforts to reduce lost to follow-up during the conduct of the trial. Following study completion, we employed regression modeling to determine predictors of perfect attendance and variables associated with being lost to follow-up. RESULTS: During the study, intensive tracing efforts were initiated after the first 1686 mother-infant pairs had been enrolled, and 327 pairs were missing. Of these pairs, 60 were located and had complete data obtained. Among the 683 participants enrolling after initiation of intensive tracing efforts, the lost to follow-up rate was 3.4%. At study's end, 290 (12.2%) of the 2369 mother-infant pairs were lost to follow-up. 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 lost to follow-up. CONCLUSION: In this large HIV prevention trial, intensive tracing efforts centered on reaching study participants at their homes succeeded in finding a substantial proportion of lost to follow-up participants and were very effective in preventing further lost to follow-up during the remainder of the trial. The association between food insecurity and lower rates of lost to follow-up is likely related to the study's provision of nutritional support, including a family maize supplement, which may have contributed to patient retention.

The HIV treatment cascade in acutely infected people: informing global guidelines.

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 fourth-generation testing and pooled nucleic acid amplification testing 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.

Antiretroviral therapy: when to start.

In this article, the scientific evidence and professional guidelines regarding the timing of antiretroviral therapy initiation are reviewed, with discussion of the increasingly persuasive evidence in favor of starting treatment early in the course of human immunodeficiency virus disease.