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.

The state of engagement in HIV care in the United States: from cascade to continuum to control.

The National HIV/AIDS Strategy and the promise of treatment as prevention have garnered considerable attention from the policy, practice, and scientific communities, with the treatment cascade becoming the sentinel image illustrating the domestic human immunodeficiency virus (HIV) epidemic. The cascade depicts prevalence estimates for sequential steps from HIV diagnosis through viral suppression, the most striking of which is that >50% of persons diagnosed with HIV are not in medical care. This heterogeneous group includes individuals not linked to medical care following HIV diagnosis and those entering care who are not retained, requiring reengagement from a range of community settings. This review synthesizes the state of engagement in HIV care in the United States, focusing on research, practice, and policy considerations. Included are conceptual frameworks, a review of health implications, measurement, monitoring, and evidence-based intervention approaches, and a look to the future in addressing the greatest challenge and opportunity facing our domestic HIV epidemic.

Transdermal penetration of vasoconstrictors--present understanding and assessment of the human epidermal flux and retention of free bases and ion-pairs.

PURPOSE: As reductions in dermal clearance increase the residence time of solutes in the skin and underlying tissues we compared the topical penetration of potentially useful vasoconstrictors (VCs) through human epidermis as both free bases and ion-pairs with salicylic acid (SA). METHODS: We determined the in vitro epidermal flux of ephedrine, naphazoline, oxymetazoline, phenylephrine, and xylometazoline applied as saturated solutions in propylene glycol:water (1:1) and of ephedrine, naphazoline and tetrahydrozoline as 10% solutions of 1:1 molar ratio ion-pairs with SA in liquid paraffin. RESULTS: As free bases, ephedrine had the highest maximal flux, Jmax = 77.4 +/- 11.7 microg/cm2/h, being 4-fold higher than tetrahydrozoline and xylometazoline, 6-fold higher than phenylephrine, 10-fold higher than naphazoline and 100-fold higher than oxymetazoline. Stepwise regression of solute physicochemical properties identified melting point as the most significant predictor of flux. As ion-pairs with SA, ephedrine and naphazoline had similar fluxes (11.5 +/- 2.3 and 12.0 +/- 1.6 microg/cm2/h respectively), whereas tetrahydrozoline was approximately 3-fold slower. Corresponding fluxes of SA from the ion-pairs were 18.6 +/- 0.6, 7.8+/- 0.8 and 1.1 +/- 0.1 respectively. Transdermal transport of VC's is discussed. CONCLUSIONS: Epidermal retention of VCs and SA did not correspond to their molar ratio on application and confirmed that following partitioning into the stratum corneum, ion-pairs separate and further penetration is governed by individual solute characteristics.