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Antiretroviral Drugs for Treatment and Prevention of HIV in Adults: 2024 Recommendations of the International Antiviral Society-USA Panel

Author/s: 
Rajesh T Gandhi, Raphael J Landovitz, Paul E Sax, Davey M Smith

Importance: New data and new antiretroviral drugs and formulations continue to become available for the prevention and management of HIV infection.

Objective: To provide updated recommendations for HIV treatment and clinical management and HIV prevention.

Methods: A panel of volunteer expert physician scientists were appointed to provide updated consensus recommendations for 2024. Relevant evidence in the literature since the last report was identified from PubMed and Embase searches (which initially yielded 3998 unique citations, of which 249 were considered relevant); from ongoing monitoring of the literature by the panel members; from data submitted by product manufacturers; and from studies presented at peer-reviewed scientific conferences between June 2022 and October 2024.

Findings: Antiretroviral therapy continues to be recommended for all individuals with HIV. For most people with HIV, initial regimens composed of an integrase strand transfer inhibitor (InSTI), specifically bictegravir or dolutegravir, with 2 (and in some cases 1) nucleoside or nucleotide reverse transcriptase inhibitors are recommended. Recommendations are made for those with particular clinical circumstances, such as pregnancy and active opportunistic diseases, as well as for those unable to take InSTIs. Regimens may need to be changed for virologic failure, adverse effects, convenience, or cost, among other reasons. Long-acting injectable therapy is available for those who prefer not to take daily oral medications and for people struggling with adherence to daily therapy. Recommendations are provided for laboratory monitoring, management of substance use disorders and weight changes, as well as use of statins for cardiovascular disease prevention. For HIV prevention, oral (daily or intermittent) and injectable long-acting medications are effective options for people at increased likelihood of HIV exposure. Further, new tools for maintaining health and well-being among people with HIV, such as doxycycline postexposure prophylaxis to avert sexually transmitted infection, and strategies to treat substance use disorders, are recommended. Disparities in HIV acquisition and care access are discussed and solutions proposed.

Conclusions: New approaches for treating and preventing HIV offer additional tools to help end the HIV epidemic, but achieving this goal depends on addressing disparities and inequities in access to care.

Keywords 
HIV Infections HIV sexually transmitted diseases

Preexposure Prophylaxis (PrEP) for HIV

Author/s: 
Matthew A Spinelli, Kenneth Ngure, Monica Gandhi

Preexposure prophylaxis (PrEP) involves use of antiviral medication for HIV prevention in HIV-negative adults or adolescents at risk for HIV through sex or injection drug use. The United Nations Programme on HIV/AIDS (UNAIDS) recently set a goal for 95% of people at risk of HIV (approximately 10 million people worldwide) to have access to and use PrEP in 2025, although only 3.5 million individuals at risk of HIV were receiving PrEP as of 2023. The UNAIDS 2024 global AIDS update reported no decrease in HIV incidence since 2021, with an estimated 1.3 million new infections reported globally in 2023.

Keywords 
prophylaxis Anti-HIV Agents HIV

Pre-exposure prophylaxis for HIV: effective and underused

Author/s: 
Hempel, A., Biondi, M. J., Baril, J., Tan, D. H. S.

Pre-exposure prophylaxis (PrEP) is a highly effective modality for HIV prevention that can be prescribed by generalists.

Pre-exposure prophylaxis should be offered to patients who are at high risk of HIV exposure, including gay, bisexual and other men who have sex with men (GBM), women reporting condomless intercourse with partners of confirmed or unknown transmissible HIV status and persons who inject drugs and share injection equipment.

Once daily PrEP (tenofovir disoproxil fumarate/emtricitabine [TDF/FTC] or tenofovir alafenamide fumarate/emtricitabine tablets) is approved by Health Canada.

On-demand TDF/FTC can be prescribed to gay, bisexual and other men who have sex with men and has similar efficacy.

The Canadian guideline details protocolized monitoring for PrEP follow-up including HIV screening, screening for sexually transmitted infection and renal monitoring.

Keywords 
Follow-Up Studies Substance Abuse, intravenous Canada sexually transmitted diseases Drug users

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

Author/s: 
Saag, Michael S., Gandhi, Rajesh T., Hoy, Jennifer F., Landovitz, Raphael J., Thompson, Melanie A., Sax, Paul E., Smith, Savey M., Benson, Constance A., Buchbinder, Susan P., Del Rio, Carlos, Eron Jr., Joseph J., Fätkenheuer, Gerd, Günthard, Huldrych F., Molina, Jean-Michel, Jacobsen, Donna M., Volberding, Paul A.

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.

Keywords 
antiretroviral drugs HIV disease COVID-19

Therapeutic use of cannabis and cannabinoids: an evidence mapping and appraisal of systematic reviews

Author/s: 
Montero-Oleas, N, Arevalo-Rodriguez, I, Nunez-Gonzalez, S, Viteri-Garcia, A, Simancas-Racines, D

Background

Although cannabis and cannabinoids are widely used with therapeutic purposes, their claimed efficacy is highly controversial. For this reason, medical cannabis use is a broad field of research that is rapidly expanding. Our objectives are to identify, characterize, appraise, and organize the current available evidence surrounding therapeutic use of cannabis and cannabinoids, using evidence maps.

Methods

We searched PubMed, EMBASE, The Cochrane Library and CINAHL, to identify systematic reviews (SRs) published from their inception up to December 2017. Two authors assessed eligibility and extracted data independently. We assessed methodological quality of the included SRs using the AMSTAR tool. To illustrate the extent of use of medical cannabis, we organized the results according to identified PICO questions using bubble plots corresponding to different clinical scenarios.

Results

A total of 44 SRs published between 2001 and 2017 were included in this evidence mapping with data from 158 individual studies. We extracted 96 PICO questions in the following medical conditions: multiple sclerosis, movement disorders (e.g. Tourette Syndrome, Parkinson Disease), psychiatry conditions, Alzheimer disease, epilepsy, acute and chronic pain, cancer, neuropathic pain, symptoms related to cancer (e.g. emesis and anorexia related with chemotherapy), rheumatic disorders, HIV-related symptoms, glaucoma, and COPD. The evidence about these conditions is heterogeneous regarding the conclusions and the quality of the individual primary studies. The quality of the SRs was moderate to high according to AMSTAR scores.

Conclusions

Evidence on medical uses of cannabis is broad. However, due to methodological limitations, conclusions were weak in most of the assessed comparisons. Evidence mapping methodology is useful to perform an overview of available research, since it is possible to systematically describe the extent and distribution of evidence, and to organize scattered data.

Keywords 
cannabis cannabinoids therapeutic use evidence mapping medical marijuana

Vaccines for International Travel

Author/s: 
Freedman, DO, Chen, LH

The pretravel management of the international traveler should be based on risk management principles. Prevention strategies and medical interventions should be based on the itinerary, preexisting health factors, and behaviors that are unique to the traveler. A structured approach to the patient interaction provides a general framework for an efficient consultation. Vaccine-preventable diseases play an important role in travel-related illnesses, and their impact is not restricted to exotic diseases in developing countries. Therefore, an immunization encounter before travel is an ideal time to update all age-appropriate immunizations as well as providing protection against diseases that pose additional risk to travelers that may be delineated by their destinations or activities. This review focuses on indications for each travel-related vaccine together with a structured synthesis and graphics that show the geographic distribution of major travel-related diseases and highlight particularly high-risk destinations and behaviors. Dosing, route of administration, need for boosters, and possible accelerated regimens for vaccines administered prior to travel are presented. Different underlying illnesses and medications produce different levels of immunocompromise, and there is much unknown in this discipline. Recommendations regarding vaccination of immunocompromised travelers have less of an evidence base than for other categories of travelers. The review presents a structured synthesis of issues pertinent to considerations for 5 special populations of traveler: child traveler, pregnant traveler, severely immunocompromised traveler, HIV-infected traveler, and traveler with other chronic underlying disease including asplenia, diabetes, and chronic liver disease.

Keywords 
vaccines travel international travel travel vaccine immunizations

Screening for HIV Infection: US Preventive Services Task Force Recommendation Statement.

Author/s: 
U. S. Preventive Services Task Force

IMPORTANCE:

Approximately 1.1 million persons in the United States are currently living with HIV, and more than 700 000 persons have died of AIDS since the first cases were reported in 1981. There were approximately 38 300 new diagnoses of HIV infection in 2017. The estimated prevalence of HIV infection among persons 13 years and older in the United States is 0.4%, and data from the Centers for Disease Control and Prevention show a significant increase in HIV diagnoses starting at age 15 years. An estimated 8700 women living with HIV give birth each year in the United States. HIV can be transmitted from mother to child during pregnancy, labor, delivery, and breastfeeding. The incidence of perinatal HIV infection in the United States peaked in 1992 and has declined significantly following the implementation of routine prenatal HIV screening and the use of effective therapies and precautions to prevent mother-to-child transmission.

OBJECTIVE:

To update the 2013 US Preventive Services Task Force (USPSTF) recommendation on screening for HIV infection in adolescents, adults, and pregnant women.

EVIDENCE REVIEW:

The USPSTF reviewed the evidence on the benefits and harms of screening for HIV infection in nonpregnant adolescents and adults, the yield of screening for HIV infection at different intervals, the effects of initiating antiretroviral therapy (ART) at a higher vs lower CD4 cell count, and the longer-term harms associated with currently recommended ART regimens. The USPSTF also reviewed the evidence on the benefits (specifically, reduced risk of mother-to-child transmission of HIV infection) and harms of screening for HIV infection in pregnant persons, the yield of repeat screening for HIV at different intervals during pregnancy, the effectiveness of currently recommended ART regimens for reducing mother-to-child transmission of HIV infection, and the harms of ART during pregnancy to the mother and infant.

FINDINGS:

The USPSTF found convincing evidence that currently recommended HIV tests are highly accurate in diagnosing HIV infection. The USPSTF found convincing evidence that identification and early treatment of HIV infection is of substantial benefit in reducing the risk of AIDS-related events or death. The USPSTF found convincing evidence that the use of ART is of substantial benefit in decreasing the risk of HIV transmission to uninfected sex partners. The USPSTF also found convincing evidence that identification and treatment of pregnant women living with HIV infection is of substantial benefit in reducing the rate of mother-to-child transmission. The USPSTF found adequate evidence that ART is associated with some harms, including neuropsychiatric, renal, and hepatic harms, and an increased risk of preterm birth in pregnant women. The USPSTF concludes with high certainty that the net benefit of screening for HIV infection in adolescents, adults, and pregnant women is substantial.

CONCLUSIONS AND RECOMMENDATION:

The USPSTF recommends screening for HIV infection in adolescents and adults aged 15 to 65 years. Younger adolescents and older adults who are at increased risk of infection should also be screened. (A recommendation) The USPSTF recommends screening for HIV infection in all pregnant persons, including those who present in labor or at delivery whose HIVstatus is unknown. (A recommendation).

Keywords 
HIV HIV prevention HIV screening

Preexposure Prophylaxis for the Prevention of HIV Infection: US Preventive Services Task Force Recommendation Statement

Author/s: 
US Preventive Services Task Force

Abstract

IMPORTANCE:

An estimated 1.1 million individuals in the United States are currently living with HIV, and more than 700 000 persons have died of AIDS since the first cases were reported in 1981. In 2017, there were 38 281 new diagnoses of HIV infection reported in the United States; 81% of these new diagnoses were among males and 19% were among females. Although treatable, HIV infection has no cure and has significant health consequences.

OBJECTIVE:

To issue a new US Preventive Services Task Force (USPSTF) recommendation on preexposure prophylaxis (PrEP) for the prevention of HIV infection.

EVIDENCE REVIEW:

The USPSTF reviewed the evidence on the benefits of PrEP for the prevention of HIV infection with oral tenofovir disoproxil fumarate monotherapy or combined tenofovir disoproxil fumarate and emtricitabine and whether the benefits vary by risk group, population subgroup, or regimen or dosing strategy; the diagnostic accuracy of risk assessment tools to identify persons at high risk of HIVacquisition; the rates of adherence to PrEP in primary care settings; the association between adherence and effectiveness of PrEP; and the harms of PrEP when used for HIV prevention.

FINDINGS:

The USPSTF found convincing evidence that PrEP is of substantial benefit in decreasing the risk of HIV infection in persons at high risk of HIV acquisition. The USPSTF also found convincing evidence that adherence to PrEP is highly associated with its efficacy in preventing the acquisition of HIV infection; thus, adherence to PrEP is central to realizing its benefit. The USPSTF found adequate evidence that PrEP is associated with small harms, including kidney and gastrointestinal adverse effects. The USPSTF concludes with high certainty that the magnitude of benefit of PrEP with oral tenofovir disoproxil fumarate-based therapy to reduce the risk of acquisition of HIV infection in persons at high risk is substantial.

CONCLUSIONS AND RECOMMENDATION:

The USPSTF recommends offering PrEP with effective antiretroviral therapy to persons at high risk of HIV acquisition. (A recommendation).

Keywords 
United States HIV HIV prevention

Management of Hepatitis C in 2019.

Author/s: 
Kristen, Naggie, Susanna

In the United States, hepatitis C virus (HCV) infection affects more than 2 million adults and is the leading cause of liver-related mortality. Therapies that eradicate HCV may prevent progression to cirrhosis, liver decompensation, hepatocellular carcinoma, need for liver transplant, and death. HCV eradication also appears to reduce the risk of extrahepatic diseases, including cryoglobulinemic vasculitis and cardiovascularevents. Direct-acting antivirals (DAAs), oral drugs that target multiple mechanisms of the HCV lifecycle, have been usedincombination since 2013. Because of their efficacy and safety, the use of DAAshas substantiall yimproved HCV treatment and made HCV eradication possible for most patients, including patients with HIV infection, severe renal and hepatic impairment, and history of organ transplantation. Individuals living with HCV should be treated to reduce liver-related and all-cause morbidity and mortality and to prevent HCV transmission...

Keywords 
Pregnancy U.S. hepatitis vaccination RNA HIV Genotype liver
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