Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2020 Recommendations of the International Antiviral Society-USA Panel.

Importance: Data on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices. Objective: To evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV. Evidence Review: New evidence was collected since the previous International Antiviral (formerly AIDS) Society-USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations. Findings: From 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic. Conclusion and Relevance: Advances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.

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

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.

HIV Treatment and Prevention: An Overview of Recommendations From the IAS-USA Antiretroviral Guidelines Panel.

Updated recommendations from the IAS-USA Antiretroviral Guidelines Panel on antiretroviral therapy for the treatment and prevention of HIV infection in adults were published in the Journal of the American Medical Association in 2016. The updated, evidence-based recommendations address when to initiate antiretroviral therapy, recommended initial antiretroviral regimens, including integrase strand transfer inhibitor (InSTI)-based regimens, recommended regimens for persons in whom an InSTI is not an option, and special treatment considerations. The interface between antiretroviral therapy and opportunistic infections, when and how to switch antiretroviral therapy, laboratory monitoring, engagement in care, adherence to antiretroviral therapy, and use of antiretroviral therapy as HIV prevention are also discussed, as well as future directions in HIV treatment. This article summarizes an IAS-USA continuing education webinar presented by Paul A. Volberding, MD, in August 2016.

A Conversation Among the IAS-USA Board of Directors: Hot Topics and Emerging Data in HIV Research and Care.

The IAS-USA volunteer Board of Directors met in October 2016 for its annual meeting. For the second year, the Board conducted a live, hour-long, interactive, roundtable webinar covering current questions and issues in HIV research, prevention, and care. Important highlights from the Board's discussion, which was moderated by Paul A. Volberding, MD, are included below. Members of the IAS-USA volunteer Board of Directors are Constance A. Benson, MD; Judith S. Currier, MD; Carlos del Rio, MD; Joel E. Gallant, MD, MPH; Roy M. Gulick, MD, MPH; Jeanne M. Marrazzo, MD, MPH; Douglas D. Richman, MD; Michael S. Saag, MD; Robert T. Schooley, MD; and Paul A. Volberding, MD.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society-USA Panel.

IMPORTANCE: New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. OBJECTIVE: To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. EVIDENCE REVIEW: A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. FINDINGS: Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure. CONCLUSIONS AND RELEVANCE: Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults.

Health impact of human rights testimony: harming the most vulnerable?

BACKGROUND: Current legal efforts to document human rights violations typically include interviews in which survivors are asked to provide detailed descriptions of their traumatic experiences during a single meeting. Research on similar interview techniques used as part of a mental health treatment (eg, debriefing) has raised concerns that they might worsen mental health-more than doubling the risk of post-traumatic stress disorder in some studies. While controversy over the mental health impact of debriefing continues, debriefing treatments have been discontinued in most clinics nearly 2 decades ago. The purpose of this article is to promote the development and integration of preventative measures to limit potential mental health damage associated with legal endeavours to address human rights violations and international crimes. METHODS AND FINDINGS: Given the recent growth of the field of global mental health and its current capacity to provide feasible, acceptable, effective care in low-resource settings, we propose a research agenda to identify the mental health impact of current human rights legal practices and test a model of scalable medicolegal care that minimises risk by integrating mental health monitoring and applying up-to-date models of trauma treatment, including multiple meeting sessions, as indicated. CONCLUSIONS: As the fields of global health, human rights law, international criminal law and transitional justice increasingly overlap in their efforts to assist communities affected by grave violence, we propose that synchronising efforts may offer important opportunities to improve mental health for survivors.

Building Networks for Global Clinical Research: The Basics.

Over the last several decades, interest in global health across all fields of medicine, including orthopaedic surgery, has grown markedly. Cross-national collaborations are an effective means of conducting high-quality clinical research and offer many advantages over single-center investigations. Successful collaboration requires a well-designed research protocol, development of an effective team structure, and the funding to ensure the project is sustained to completion. Equally important, investigators must consider the social, linguistic, and cultural context in which the study is being undertaken. Although randomized clinical trials are the highest level of evidence, study designs may have to be adapted to accommodate available resources, expertise, and local contextual factors. With appropriate planning, these collaborative endeavors can generate changes in clinical practice and positively impact health policy.

Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel.

IMPORTANCE: New data and antiretroviral regimens expand treatment choices in resource-rich settings and warrant an update of recommendations to treat adults infected with human immunodeficiency virus (HIV). OBJECTIVE: To provide updated treatment recommendations for adults with HIV, emphasizing when to start treatment; what treatment to start; the use of laboratory monitoring tools; and managing treatment failure, switches, and simplification. DATA SOURCES, STUDY SELECTION, AND DATA SYNTHESIS: An International Antiviral Society-USA panel of experts in HIV research and patient care considered previous data and reviewed new data since the 2012 update with literature searches in PubMed and EMBASE through June 2014. Recommendations and ratings were based on the quality of evidence and consensus. RESULTS: Antiretroviral therapy is recommended for all adults with HIV infection. Evidence for benefits of treatment and quality of available data increase at lower CD4 cell counts. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (NRTIs; abacavir/lamivudine or tenofovir disoproxil fumarate/emtricitabine) and a third single or boosted drug, which should be an integrase strand transfer inhibitor (dolutegravir, elvitegravir, or raltegravir), a nonnucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine) or a boosted protease inhibitor (darunavir or atazanavir). Alternative regimens are available. Boosted protease inhibitor monotherapy is generally not recommended, but NRTI-sparing approaches may be considered. New guidance for optimal timing of monitoring of laboratory parameters is provided. Suspected treatment failure warrants rapid confirmation, performance of resistance testing while the patient is receiving the failing regimen, and evaluation of reasons for failure before consideration of switching therapy. Regimen switches for adverse effects, convenience, or to reduce costs should not jeopardize antiretroviral potency. CONCLUSIONS AND RELEVANCE: After confirmed diagnosis of HIV infection, antiretroviral therapy should be initiated in all individuals who are willing and ready to start treatment. Regimens should be selected or changed based on resistance test results with consideration of dosing frequency, pill burden, adverse toxic effect profiles, comorbidities, and drug interactions.

Highlights of the 2014 International AIDS Conference: update from down under.

The 20th International AIDS Conference held in Melbourne, Australia, from July 20 through July 25, 2014, provided much new data on nucleoside analogue reverse transcriptase inhibitor-sparing antiretroviral therapy, potential consequences of switching suppressive antiretroviral regimen, antiretroviral treatment with integrase strand transfer inhibitors, effects of antiretroviral therapy on HIV-associated neurocognitive impairment, and hepatitis C virus (HCV) treatment in HIV/HCV-coinfected individuals. This article summarizes an IAS-USA continuing education webinar presented by Paul A. Volberding, MD, in August 2014, in which he focused on a few select highlights from the Conference.

Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel.

CONTEXT: New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected adults in resource-rich settings. OBJECTIVE: To provide current recommendations for the treatment of adult HIV infection with ART and use of laboratory-monitoring tools. Guidelines include when to start therapy and with what drugs, monitoring for response and toxic effects, special considerations in therapy, and managing antiretroviral failure. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Data that had been published or presented in abstract form at scientific conferences in the past 2 years were systematically searched and reviewed by an International Antiviral Society-USA panel. The panel reviewed available evidence and formed recommendations by full panel consensus. DATA SYNTHESIS: Treatment is recommended for all adults with HIV infection; the strength of the recommendation and the quality of the evidence increase with decreasing CD4 cell count and the presence of certain concurrent conditions. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir). Alternatives in each class are recommended for patients with or at risk of certain concurrent conditions. CD4 cell count and HIV-1 RNA level should be monitored, as should engagement in care, ART adherence, HIV drug resistance, and quality-of-care indicators. Reasons for regimen switching include virologic, immunologic, or clinical failure and drug toxicity or intolerance. Confirmed treatment failure should be addressed promptly and multiple factors considered. CONCLUSION: New recommendations for HIV patient care include offering ART to all patients regardless of CD4 cell count, changes in therapeutic options, and modifications in the timing and choice of ART in the setting of opportunistic illnesses such as cryptococcal disease and tuberculosis.

Clinician attitudes about commercial support of continuing medical education: results of a detailed survey.

BACKGROUND: Pharmaceutical and medical device company funding supports up to 60% of accredited continuing medical education (CME) costs in the United States. Some have proposed measures to limit the size, scope, and potential influence of commercial support for CME activities. We sought to determine whether participants at CME activities perceive that commercial support introduces bias, whether this is affected by the amount or type of support, and whether they would be willing to accept higher fees or fewer amenities to decrease the need for such funding. METHODS: We delivered a structured questionnaire to 1347 participants at a series of 5 live CME activities about the impact of commercial support on bias and their willingness to pay additional amounts to eliminate the need for commercial support. RESULTS: Of the 770 respondents (a 57% response rate), most (88%) believed that commercial support introduces bias, with greater amounts of support introducing greater risk of bias. Only 15%, however, supported elimination of commercial support from CME activities, and less than half (42%) were willing to pay increased registration fees to decrease or eliminate commercial support. Participants who perceived bias from commercial support more frequently agreed to increase registration fees to decrease such support (2- to 3-fold odds ratio). Participants greatly underestimated the costs of ancillary activities, such as food, as well as the degree of support actually provided by commercial funding. CONCLUSION: Although the medical professionals responding to this survey were concerned about bias introduced from commercial funding of CME, many were not willing to pay higher fees to offset or eliminate such funding sources.

Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel.

CONTEXT: Recent data regarding the consequences of untreated human immunodeficiency virus (HIV) infection and the expansion of treatment choices for antiretroviral-naive and antiretroviral-experienced patients warrant an update of the International AIDS Society-USA guidelines for the use of antiretroviral therapy in adults with HIV infection. OBJECTIVES: To provide updated recommendations for management of HIV-infected adults, using antiretroviral drugs and laboratory monitoring tools available in the international, developed-world setting. This report provides guidelines for when to initiate antiretroviral therapy, selection of appropriate initial regimens, patient monitoring, when to change therapy, and what regimens to use when changing. DATA SOURCES AND STUDY SELECTION: A panel with expertise in HIV research and clinical care reviewed relevant data published or presented at selected scientific conferences since the last panel report through April 2010. Data were identified through a PubMed search, review of scientific conference abstracts, and requests to antiretroviral drug manufacturers for updated clinical trials and adverse event data. DATA EXTRACTION AND SYNTHESIS: New evidence was reviewed by the panel. Recommendations were drafted by section writing committees and reviewed and edited by the entire panel. The quality and strength of the evidence were rated and recommendations were made by full panel consensus. CONCLUSIONS: Patient readiness for treatment should be confirmed before initiation of antiretroviral treatment. Therapy is recommended for asymptomatic patients with a CD4 cell count < or = 500/microL, for all symptomatic patients, and those with specific conditions and comorbidities. Therapy should be considered for asymptomatic patients with CD4 cell count > 500/microL. Components of the initial and subsequent regimens must be individualized, particularly in the context of concurrent conditions. Patients receiving antiretroviral treatment should be monitored regularly; treatment failure should be detected and managed early, with the goal of therapy, even in heavily pretreated patients, being HIV-1 RNA suppression below commercially available assay quantification limits.

Antiretroviral therapy and management of HIV infection.

Antiretroviral therapy of HIV infection has changed a uniformly fatal into a potentially chronic disease. There are now 17 drugs in common use for HIV treatment. Patients who can access and adhere to combination therapy should be able to achieve durable, potentially lifelong suppression of HIV replication. Despite the unquestioned success of antiretroviral therapy, limitations persist. Treatment success needs strict lifelong drug adherence. Although the widely used drugs are generally well tolerated, most have some short-term toxic effects and all have the potential for both known and unknown long-term toxic effects. Drug and administration costs limit treatment in resource-poor regions, and are a growing concern even in resource rich settings. Finally, complete or near complete control of viral replication does not fully restore health. Long-term treated patients who are on an otherwise effective regimen often show persistent immune dysfunction and have higher than expected risk for various non-AIDS-related complications, including heart, bone, liver, kidney, and neurocognitive diseases.

Long-term clinical consequences of acute kidney injury in the HIV-infected.

To evaluate the long-term consequences of acute kidney injury (AKI) in human immunodeficiency virus (HIV)-infected persons, we studied 17,325 patients in a national HIV registry during their first hospitalization. We determined the association of AKI with risk for heart failure, cardiovascular events, end-stage renal disease (ESRD), and mortality beginning 90 days after discharge. Based on AKI Network criteria, 2453 had stage 1; 273 had stage 2 or 3; and 334 had dialysis-requiring AKI. Over a mean follow-up period of 5.7 years, 333 had heart failure, 673 had cardiovascular diseases (CVDs), 348 developed ESRD, and 8405 deaths occurred. In multivariable-adjusted analyses, AKI stage 1 was associated with death and ESRD, but not heart failure or other CVD. Dialysis-requiring AKI had much stronger and significant associations with increased risk for long-term ESRD, and death in addition to heart failure and cardiovascular events. When AKI was reclassified to account for recovery, stage 1 with recovery was still associated with death, but not ESRD. Thus, in this national sample of HIV-infected persons, we found the clinical repercussions of AKI appear to extend beyond the hospital setting contributing to excess cardiovascular risks, ESRD, and mortality. Additionally, AKI affected almost one of six patients with HIV who survived at least 90 days following discharge.