Importance Antiretroviral therapy (ART) is the cornerstone of prevention and management of HIV infection. Objective To evaluate new data and treatments and incorporate this information into updated recommendations for initiating therapy, monitoring individuals starting therapy, changing regimens, and preventing HIV infection for individuals at risk. Evidence Review New evidence collected since the International Antiviral Society–USA 2016 recommendations via monthly PubMed and EMBASE literature searches up to April 2018; data presented at peer-reviewed scientific conferences. A volunteer panel of experts in HIV research and patient care considered these data and updated previous recommendations. Findings ART is recommended for virtually all HIV-infected individuals, as soon as possible after HIV diagnosis. Immediate initiation (eg, rapid start), if clinically appropriate, requires adequate staffing, specialized services, and careful selection of medical therapy. An integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is generally recommended for initial therapy, with unique patient circumstances (eg, concomitant diseases and conditions, potential for pregnancy, cost) guiding the treatment choice. CD4 cell count, HIV RNA level, genotype, and other laboratory tests for general health and co-infections are recommended at specified points before and during ART. If a regimen switch is indicated, treatment history, tolerability, adherence, and drug resistance history should first be assessed; 2 or 3 active drugs are recommended for a new regimen. HIV testing is recommended at least once for anyone who has ever been sexually active and more often for individuals at ongoing risk for infection. Preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine and appropriate monitoring is recommended for individuals at risk for HIV. Conclusions and Relevance Advances in HIV prevention and treatment with antiretroviral drugs continue to improve clinical management and outcomes for individuals at risk for and living with HIV.

/pdf/antiretroviral-drugs-for-treatment-and-prevention-of-hiv-1glh5twgkc.pdf

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2018 Recommendations of the International Antiviral Society–USA Panel

Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380–1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial

Background:Recent attention has focused on the question of how quickly antiretroviral therapy (ART) should be started once HIV diagnosis is confirmed. We assessed whether rapid ART initiation improves patient outcomes.Methods:We searched five databases from inception up to August 2017. Rapid ART ini

/pdf/benefits-and-risks-of-rapid-initiation-of-antiretroviral-16pb6zdpf6.pdf

Benefits and risks of rapid initiation of antiretroviral therapy.

Author(s): Henrich, Timothy J; Hatano, Hiroyu; Bacon, Oliver; Hogan, Louise E; Rutishauser, Rachel; Hill, Alison; Kearney, Mary F; Anderson, Elizabeth M; Buchbinder, Susan P; Cohen, Stephanie E; Abdel-Mohsen, Mohamed; Pohlmeyer, Christopher W; Fromentin, Remi; Hoh, Rebecca; Liu, Albert Y; McCune, Joseph M; Spindler, Jonathan; Metcalf-Pate, Kelly; Hobbs, Kristen S; Thanh, Cassandra; Gibson, Erica A; Kuritzkes, Daniel R; Siliciano, Robert F; Price, Richard W; Richman, Douglas D; Chomont, Nicolas; Siliciano, Janet D; Mellors, John W; Yukl, Steven A; Blankson, Joel N; Liegler, Teri; Deeks, Steven G | Abstract: BackgroundIt is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 days (Participant B; 31-year-old male) after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI) following 32 weeks of continuous ART.Methods and findingsColorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF), plasma, and very large numbers of peripheral blood mononuclear cells (PBMCs) were obtained longitudinally from both participants and were studied for HIV persistence in several laboratories using molecular and culture-based detection methods, including a murine viral outgrowth assay (mVOA). Both participants initiated PrEP with tenofovir/emtricitabine during very early Fiebig stage I (detectable plasma HIV-1 RNA, antibody negative) followed by 4-drug ART intensification. Following peak viral loads, both participants experienced full suppression of HIV-1 plasma viremia. Over the following 2 years, no further HIV could be detected in blood or tissue from PrEP Participant A despite extensive sampling from ileum, rectum, lymph nodes, bone marrow, CSF, circulating CD4+ T cell subsets, and plasma. No HIV was detected from tissues obtained from PrEP Participant B, but low-level HIV RNA or DNA was intermittently detected from various CD4+ T cell subsets. Over 500 million CD4+ T cells were assayed from both participants in a humanized mouse outgrowth assay. Three of 8 mice infused with CD4+ T cells from PrEP Participant B developed viremia (50 million input cells/surviving mouse), but only 1 of 10 mice infused with CD4+ T cells from PrEP Participant A (53 million input cells/mouse) experienced very low level viremia (201 copies/mL); sequence confirmation was unsuccessful. PrEP Participant A stopped ART and remained aviremic for 7.4 months, rebounding with HIV RNA of 36 copies/mL that rose to 59,805 copies/mL 6 days later. ART was restarted promptly. Rebound plasma HIV sequences were identical to those obtained during acute infection by single-genome sequencing. Mathematical modeling predicted that the latent reservoir size was approximately 200 cells prior to ATI and that only around 1% of individuals with a similar HIV burden may achieve lifelong ART-free remission. Furthermore, we observed that lymphocytes expressing the tumor marker CD30 increased in frequency weeks to months prior to detectable HIV-1 RNA in plasma. This study was limited by the small sample size, which was a result of the rarity of individuals presenting during hyperacute infection.ConclusionsWe report HIV relapse despite initiation of ART at one of the earliest stages of acute HIV infection possible. Near complete or complete loss of detectable HIV in blood and tissues did not lead to indefinite ART-free HIV remission. However, the small numbers of latently infected cells in individuals treated during hyperacute infection may be associated with prolonged ART-free remission.

/pdf/hiv-1-persistence-following-extremely-early-initiation-of-12fw391ldv.pdf

HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART) during acute HIV-1 infection: An observational study

These guidelines are intended as an update to those published in the Southern African Journal of HIV Medicine in 2014 and the update on when to initiate antiretroviral therapy in 2015. Since the release of the previous guidelines, the scale-up of antiretroviral therapy (ART) in southern Africa has continued. New antiretroviral drugs have become available with improved efficacy, safety and robustness. The guidelines are intended for countries in the southern African region, which vary between lower and middle income.

/pdf/adult-antiretroviral-therapy-guidelines-2017-d6lp33u9rp.pdf

Adult antiretroviral therapy guidelines 2017

Background Antiretroviral therapy (ART) is typically begun weeks after HIV diagnosis. We assessed the acceptability, feasibility, safety, and efficacy of initiating ART on the same day as diagnosis. Methods We studied a clinic-based cohort consisting of consecutive patients who were referred with new HIV diagnosis between June 2013 and December 2014. A subset of patients with acute or recent infection ( Results Among 86 patients, 39 were eligible and managed on the RAPID protocol. Thirty-seven (94.9%) of 39 in RAPID began ART within 24 hours. Minor toxicity with the initial regimen occurred in 2 (5.1%) of intervention patients versus none in the nonintervention group. Loss to follow-up was similar in intervention (10.3%) and nonintervention patients (14.9%) during the study. Time to virologic suppression ( Conclusions Treatment for HIV infection can be started on the day of diagnosis without impacting the safety or acceptability of ART. Same-day ART may shorten the time to virologic suppression.

/pdf/the-effect-of-same-day-observed-initiation-of-antiretroviral-44gwkczrfo.pdf

The Effect of Same-Day Observed Initiation of Antiretroviral Therapy on HIV Viral Load and Treatment Outcomes in a US Public Health Setting

Immune checkpoint inhibitor (ICI) therapies are now first-line therapy for many advanced malignancies in adults, with emerging use in children. With increasing ICI use, prompt recognition and optimal management of ICI-associated immune-related adverse events (IRAEs) are critical. Nearly 60% of ICI-treated adults develop IRAEs, which commonly manifest as autoimmune skin, gastrointestinal, and endocrine disease and can be life-threatening. The incidence, presentation, and disease course of spontaneous autoimmune diseases differ between adults and children, but the pattern of pediatric IRAEs is currently unclear. We report a case of a pediatric patient presenting with new onset autoimmune diabetes mellitus and diabetic ketoacidosis during ICI treatment of fibrolamellar hepatocellular carcinoma (FLC). Distinct from spontaneous type 1 diabetes mellitus (T1DM), this patient progressed rapidly and was negative for known β cell autoantibodies. Additionally, the patient was positive for 21-hydroxylase autoantibodies, suggesting development of concomitant adrenal autoimmunity. Current guidelines for the management of IRAEs in adults may not be appropriate for the management of pediatric patients, who may have different autoimmune risks in a developmental context.

Aditi Dasgupta

Papers

The Effect of Same-Day Observed Initiation of Antiretroviral Therapy on HIV Viral Load and Treatment Outcomes in a US Public Health Setting

Polyendocrine Autoimmunity and Diabetic Ketoacidosis Following Anti-PD-1 and Interferon α.