OBJECTIVE:The objective of this study is to review the efficacy and safety of doravirine/islatravir for the treatment of HIV-1 infection. DATA SOURCES:A literature search was conducted in PubMed and Google Scholar (January 2016-June 2026) using the search terms doravirine or MK-1439 and islatravir or MK-8591. Other resources included abstracts presented at recent conferences and the prescribing information. STUDY SELECTION AND DATA EXTRACTION:All English-language studies assessing the efficacy and safety of doravirine/islatravir for the treatment of HIV-1 infection were included. DATA SYNTHESIS:Doravirine is an established second-generation nonnucleoside reverse transcriptase inhibitor. Islatravir is a new nucleoside reverse transcriptase inhibitor that uniquely interferes with translocation and is highly active against HIV-1. Doravirine/islatravir once daily was shown to be safe and effective in three phase 3 clinical trials, using a lower dose of islatravir (0.25 mg), after a higher dose (0.75 mg) was shown in earlier trials to reduce total lymphocyte and CD4+ T-cell counts. The FDA approved this combination for the treatment of HIV-1 infection in adults who are virologically suppressed on stable antiretroviral therapy with no history of virologic treatment failure and no known resistance to doravirine.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:Doravirine/islatravir is the first integrase strand transfer inhibitor-free 2-drug regimen indicated for the treatment of HIV-1 infection. The combination could be useful for patients who want to simplify their regimen and those who cannot receive an integrase inhibitor. CONCLUSIONS:Doravirine/islatravir is safe and effective as a 2-drug regimen for the treatment of HIV-1 infection.

OBJECTIVE:To review the efficacy and safety of lenacapavir for the prevention of HIV-1 infection. DATA SOURCES:Clinical trials and review articles were obtained through August 2025 using search terms lenacapavir, GS-CA1, GS-6207, capsid inhibitor, preexposure prophylaxis, and PrEP. STUDY SELECTION AND DATA EXTRACTION:All relevant articles, trials, and abstracts in the English language were included. DATA SYNTHESIS:Lenacapavir uses a novel mechanism for HIV prevention administered through subcutaneous injection. In a counterfactual design, lenacapavir arms demonstrated superior efficacy for prevention against a background HIV incidence rate across a variety of populations and gender identities. Adverse events commonly reported include injection-site reactions, which may include nodules, pain, or swelling at the injection site.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:The extended dosing frequency of lenacapavir may uniquely serve patients at risk of HIV acquisition who are unable or unwilling to take oral prevention medications. The mechanism of action for lenacapavir is not duplicative of other medications used in first-line antiretroviral regimens and thus may not risk resistance to regularly used classes if resistance occurs. Lenacapavir is a moderate cytochrome P450 inhibitor and thus may have interactions with other medications; however, neither renal nor hepatic dose adjustments are required. CONCLUSIONS:Lenacapavir provides a long-acting injectable option for people seeking a pharmacologic prevention agent against HIV-1. Despite injection-site reactions being relatively common, these did not present a barrier to treatment continuation among trial participants.

Five long-acting (LA) antiretrovirals (ARVs) are currently available in a limited number of countries worldwide for HIV-1 prevention or treatment-cabotegravir, rilpivirine, lenacapavir, ibalizumab, and dapivirine. Implementing use of LA ARVs into routine clinical practice requires significant changes to the current framework of HIV-1 prevention, treatment, and service provision. Given the novelty, complexity, and interdisciplinary requirements needed to safely and optimally utilize LA ARVs, consensus recommendations on the use of LA ARVs will assist clinicians in optimizing use of these agents. The purpose of these recommendations is to provide guidance for the clinical use of LA ARVs for HIV-1 treatment and prevention. In addition, future areas of research are also identified and discussed.

Abstract This chapter opens with a discussion about classes and mechanisms of antiretroviral agents. The mechanisms of action of the traditional versus newer antiretroviral classes is reviewed as well as the five major categories of antiretroviral agents. Key characteristics and findings of recent clinical trials from the US Department of Health and Human Services recommended regimens are reported. The topics of pharmacokinetics, pharmacodynamics, and pharmacogenomics are reviewed for the reader. Long-acting intramuscular (LAI) cabotegravir and rilpivirine are a novel, two-drug regimen containing an integrase strand transfer inhibitor and nonnucleoside reverse transcriptase inhibitor (NNRTI), respectively, that can be administered to PWH virologically suppressed on an oral ARV regimen. The combination of these LAI ARVs is approved to be administered every month or every two months. The chapter concludes with the topics of ARV dosing, coformulations, clinical trial design, and access programs to medicines in clinical trial development.

Abstract This chapter discusses the issues determining the relative priority of initiating and/or maintaining antiretroviral therapy in the context of hospitalized people with HIV with significant comorbid conditions as well as the continuity of care after discharge from the impatient setting. The chapter defines the antiretroviral stewardship and allows the learner to understand its potential benefit in implementation. It describes important consideration in the preoperative, perioperative, and postoperative care of people with HIV. An updated link to a reference table of available antiretroviral therapy (ART) formulations is provided. New ART agents since the last publication are incorporated in the chapter, and an additional resource regarding known absorption sites of ARVs, as well as pharmacokinetic effects of bariatric surgery on ARV, is provided. Lastly, the chapter describes the pharmacologic complications that may result from bariatric surgery.

Objective: To review the efficacy, safety, and role of lenacapavir (LEN) in the treatment of HIV-1 infection. Data Sources: A literature search was performed using PubMed and Google Scholar (through March 2023) with the search term LEN and GS-6207. Other resources included abstracts presented at recent conferences, the manufacturer's Web site, and prescribing information. Study Selection and Data Extraction: All relevant articles, trial updates, and conference abstracts in the English language were included. Data Synthesis: Lenacapavir represents a new class of antiretrovirals (ARVs) with a novel mechanism of action as a capsid inhibitor and a unique twice-a-year subcutaneous administration schedule. Lenacapavir when combined with other ARVs has proven to benefit heavily treatment-experienced (HTE) patients with HIV-1 infection in achieving viral suppression and immune restoration. Relevance to Patient Care and Clinical Practice in Comparison With Existing Drugs: Lenacapavir is a new treatment option that patients who are HTE can consider adding as part of an ARV regimen. Conclusions: Lenacapavir is an effective and well-tolerated option for HTE patients which is a valuable addition to the arsenal of ARVs.

Although decreasing in prevalence, heavily treatment-experienced (HTE) persons with limited options for HIV treatment present unique complexities, even amongst experienced providers, as there is no single approach to successful management. HTE patients are described as those having two or less antiretroviral (ARV) classes available for use with limited fully active ARV agents within each class. A detailed understanding of the underlying processes that caused previous treatment failures, diagnostics to define resistance, resistance mechanisms and ARV pharmacology should all function in tandem to determine the next steps of clinical care. This narrative review provides an overview of the clinician approach to care, including diagnostics, approaches to regimen creation, relevant resources, and a broad array of both currently available and upcoming ARVs that may be used in regimens for HTE patients.

Abstract This chapter discusses the issues involved in determining the relative priority of initiating and/or maintaining antiretroviral therapy in hospitalized people with HIV with significant comorbid conditions as well as the continuity of care after discharge from the inpatient setting. It defines antiretroviral stewardship and allows the learner to understand its potential benefit in implementation. Important consideration in the preoperative care of people with HIV are described. Lastly, the chapter covers the pharmacologic complications that may result from bariatric surgery.

Objective To review the efficacy and safety of fostemsavir (FTR) for the treatment of multidrug-resistant HIV-1 infection in heavily treatment-experienced adults who are failing their current antiretroviral regimen. Data Sources Clinical trials and review articles were obtained through PubMed (2015 to July 2020) using the search termsfostemsavir, BMS-663068, andGSK3684934. Study Selection and Data Extraction All relevant articles, trials, and abstracts in the English language were included. Data Synthesis FTR demonstrates a novel mechanism of action, preventing virus attachment to the host CD4 receptor. FTR extended-release 600-mg tablets every 12 hours orally has proven beneficial in obtaining viral suppression for heavily treatment-experienced patients with multidrug-resistant infection refractory to other agents, as indicated in phase 3 trials. Treatment courses were evaluated to 96 weeks with significant viral load reductions noted within the first 24 weeks. Adverse events commonly reported include nausea, vomiting, diarrhea, fatigue, and headache. Serious events and fatality were not attributed to FTR and occurred because of advancement of HIV or other acute infection. Relevance to Patient Care and Clinical Practice FTR presents a new treatment option for patients with multidrug resistance and intolerability to other medications. The favorable adverse effect profile of FTR alongside the limited drug interaction profile makes it a viable option in a salvage regimen. Conclusions FTR provides an alternative agent when composing a regimen for patients with multidrug-resistant HIV-1 infection. It is generally well tolerated, with few significant interactions, and neither renal nor hepatic dose adjustments are required.

Limited data exist regarding the use of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) in patients who are unable to swallow tablets. This case series describes HCV treatment in patients requiring tablet manipulation, providing evidence for safety and effectiveness of HCV DAA tablet manipulation.

Abstract This chapter provides an overview of what antiretroviral therapy (ART) is and the current treatment guidelines according to the US Department of Health and Human Services and the International Antiviral Society-USA. Important criteria in selecting an initial treatment regimen are discussed as well as when to switch or simplify the regimen. Factors to consider when selecting an antiretroviral regimen and other information involving ART is presented to the reader via tables.

BACKGROUND:People living with human immunodeficiency virus (HIV) may have numerous risk factors for acquiring coronavirus disease 2019 (COVID-19) and developing severe outcomes, but current data are conflicting.METHODS:Health-care providers enrolled consecutively, by nonrandom sampling, people living with HIV (PWH) with lab-confirmed COVID-19, diagnosed at their facilities between 1 April and 1 July 2020. Deidentified data were entered into an electronic Research Electronic Data Capture (REDCap) system. The primary endpoint was a severe outcome, defined as a composite endpoint of intensive care unit (ICU) admission, mechanical ventilation, or death. The secondary outcome was the need for hospitalization.RESULTS:There were 286 patients included; the mean age was 51.4 years (standard deviation, 14.4), 25.9% were female, and 75.4% were African American or Hispanic. Most patients (94.3%) were on antiretroviral therapy, 88.7% had HIV virologic suppression, and 80.8% had comorbidities. Within 30 days of testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 164 (57.3%) patients were hospitalized, and 47 (16.5%) required ICU admission. Mortality rates were 9.4% (27/286) overall, 16.5% (27/164) among those hospitalized, and 51.5% (24/47) among those admitted to an ICU. The primary composite endpoint occurred in 17.5% (50/286) of all patients and 30.5% (50/164) of hospitalized patients. Older age, chronic lung disease, and hypertension were associated with severe outcomes. A lower CD4 count (<200 cells/mm3) was associated with the primary and secondary endpoints. There were no associations between the ART regimen or lack of viral suppression and the predefined outcomes.CONCLUSIONS:Severe clinical outcomes occurred commonly in PWH with COVID-19. The risks for poor outcomes were higher in those with comorbidities and lower CD4 cell counts, despite HIV viral suppression.CLINICAL TRIALS REGISTRATION:NCT04333953.

Patient acceptance of long-acting injectable antiretroviral (LAI-ARV) HIV-1 regimens will determine uptake. Although previous literature reports high satisfaction, these data stem from clinical trials subject to selection bias. This cross-sectional survey from the HIV practices of an urban academic medical center assessed perceptions and preferences using Likert scales toward overall acceptability, proposed frequencies, injection-site reaction durations, and distribution venue. 59% of surveys were completed resulting 202 respondents. 60% were male, 72% black, and the median age was 49 (IQR 36-58). 93% reported a once daily tablet frequency, 69% reported single tablet regimens, and 59% reported missing zero doses in the prior 30 days. Patients self-categorized as likely (57%) or unlikely (43%) to accept LAI-ARV. Both decreasing frequencies between injections and durations of injection-site reactions resulted higher acceptability scores. 57% of respondents preferred receiving an injectable from their clinician’s office over other potential options. These data demonstrate positive LAI-ARV acceptance potential.

Introduction: Hepatitis C virus (HCV), the leading cause of advanced liver disease, has enormous economic burden. Identification of patients at risk of treatment failure could lead to interventions that improve cure rates. Objectives: Our goal was to develop and evaluate a prediction model for HCV treatment failure. Methods: We analyzed HCV patients initiating direct-acting antiviral therapy at four United States institutions. Treatment failure was determined by lack of sustained virologic response (SVR) 12 weeks after treatment completion. From 20 patient-level variables collected before treatment initiation, we identified a subset associated with treatment failure in bivariate analyses. In a derivation set, separate predictive models were developed from 100 bootstrap samples using logistic regression. From the 100 models, variables were ranked by frequency of selection as predictors to create four final candidate models, using cutoffs of ≥80%, ≥50%, ≥40%, and all variables. In a validation set, predictive performance was compared across models using area under the receiver operating characteristic curve. Results: In 1,253 HCV patients, overall SVR rate was 86.1% (95% CI = 84.1%, 88.0%). The AUCs of the four final candidate models were: ≥80% = 0.576; ≥50% = 0.605; ≥40% = 0.684; all = 0.681. The best performing model (≥40%) had significantly better predictive ability than the ≥50% (p = 0.03) and ≥80% models (p = 0.02). Strongest predictors of treatment failure were older age, history of hepatocellular carcinoma, and private (vs. government) insurance. Conclusion: This study highlighted baseline factors associated with HCV treatment failure. Treatment failure prediction may facilitate development of data-driven clinical tools to identify patients who would benefit from interventions to improve SVR rates.

Two-drug antiretroviral (ARV) regimens to achieve and maintain HIV viral suppression may lead to decreases in associated drug interactions, adverse events, and pill burden. Dolutegravir-lamivudine (DTG-3TC) has been established as safe and effective in treatment naïve and experienced adults. Further research is warranted to assess insertion into real-world practice. This descriptive retrospective cohort consisted of all patients at an academic medical center HIV practice with a confirmed order of DTG-3TC between April 2019 and March 2020. Patients who were not linked to care by the site’s practices were excluded. The primary endpoint was number of patients initiated on DTG-3TC to determine uptake. Secondary endpoints included demographics and viral outcomes. Descriptive measures of central tendencies and variability were used for analysis. DTG-3TC was initiated in 49 patients. Sixty-nine percent were male (34/49), 90% carried publicly funded insurance (44/49), median age at DTG-3TC initiation was 55 years (IQR 46-60), and mean years since HIV diagnosis was 14 (SD ±8). The largest racial/ethnic category represented was Black (45%, 22/49). Forty-seven patients with a mean CD4 of 753 cells/mm3 (±413) and viral load of 88.2 copies/mL (±525) were switched from alternative regimens, mostly containing an integrase inhibitor (41/47, 87%), and with the primary rationale of medication modernization (27/47, 58%) followed by avoidance of adverse drug reactions (15/47, 32%). From 42 assessed patients, 62% had previous ARV exposure length of over 10 years. No patients were found to have significant resistance mutations to the involved agents. After initiation, 6% (3/49) of patients reported side effects. Among switch patients with follow up lab values, median CD4 (n=20) and viral load (n=21) deltas were -10 cells/mm3 (-59-67) and 0 copies/mL (0-0) respectively. Overall median length of therapy through April 1, 2020 was 110 days (71-156). Initial implementation of DTG-3TC was successful in a northeast academic HIV practice primarily among virally suppressed treatment switch patients with long exposures to ARV and time since diagnosis. No clinically relevant change in CD4 or Viral Loads were immediately seen. David E. Koren, PharmD, BCPS, AAHIVP, Gilead Sciences (Advisor or Review Panel member)Janssen Pharmaceuticals (Advisor or Review Panel member)Thera Technologies (Advisor or Review Panel member)

Persons living with human immunodeficiency virus (HIV) and others receiving antiretrovirals are at risk for medication errors during hospitalization and at transitions of care. These errors may result in adverse effects or viral resistance, limiting future treatment options. A range of interventions is described in the literature to decrease the occurrence or duration of medication errors, including review of electronic health records, clinical checklists at care transitions, and daily review of medication lists. To reduce the risk of medication-related errors, antiretroviral stewardship programs (ARVSPs) are needed to enhance patient safety. This call to action, endorsed by the Infectious Diseases Society of America, the HIV Medicine Association, and the American Academy of HIV Medicine, is modeled upon the success of antimicrobial stewardship programs now mandated by the Joint Commission. Herein, we propose definitions of ARVSPs, suggest resources for ARVSP leadership, and provide a summary of published, successful strategies for ARVSP that healthcare facilities may use to develop locally appropriate programs.