HIV e IST

Abstract

Purpose: This narrative review addresses post-2020, specific, complex challenges for use of and adherence to pre-exposure prophylaxis (PrEP) for HIV prevention among out-of-treatment people who use drugs (PWUD) at syringe services programs (SSPs).

Recent findings: The COVID-19 pandemic and its associated changes to the provision of healthcare have significantly impacted HIV prevention, especially for PWUD. Through a synthesis of literature and clinical experience, we (1) characterize the operational changes imposed by the pandemic on SSPs that shaped the current HIV prevention landscape; (2) describe three levels of current challenges for PWUD, including consumer attitudes, non-medical and medical provider attitudes, and structural and scalability barriers; (3) characterize current models for PrEP in SSPs; and (4) offer practical recommendations for HIV prevention in harm reduction programs. PrEP is a highly effective prevention tool if taken as prescribed. It has been enthusiastically promoted by members of the research, public health and provider communities. Despite its efficacy, PWUD struggle to engage with the PrEP care continuum. We highlight opportunities to advance HIV prevention for PWUD by enhancing tailored, whole-person approaches that may set aside PrEP in favor of other risk reduction routes. For most PWUD who receive services at SSPs, PrEP is a single tool and not realistic until other social and structural determinants of health are addressed.

Keywords: HIV pre-exposure prophylaxis (PrEP); HIV prevention; Harm reduction; People who inject drugs; People who use drugs; Syringe services programs.

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Abstract

New human immunodeficiency virus (HIV) cases related to injection drug use (IDU) in the United States increased between 2016 and 2022. The uptake of preexposure prophylaxis (PrEP) is exceedingly low in persons who inject drugs (PWID) despite its efficacy to prevent HIV. There are multilevel barriers in the PrEP care cascade for PWID. We need a combination of effective HIV prevention strategies, including PrEP, treatment for substance use disorder, and syringe services programs (SSP) to reverse the trend. A major challenge is the lack of knowledge and skills in harm reduction practices and addiction care in the infectious disease (ID) workforce. ID clinicians could benefit from education in harm reduction and addiction, including taking on the responsibility of prescribing buprenorphine or navigating the resources for it. Addiction clinicians could benefit from education on PrEP and related program implementation knowledge. Both specialties need to comprehensively evaluate and address the risks for HIV acquisition in PWID. We should create integrated clinical programs between ID and addiction. We should improve HIV screening for hospitalized PWID. We should expand low-barrier integrated clinics with flexible hours, walk-in appointments, same-day PrEP starts, and collocated laboratory and pharmacy services. Other entities that could provide integrated care include substance detoxification and rehabilitation programs, SSPs, opioid treatment programs (OTP), community pharmacies, and mobile health clinics. Long-acting injectable PrEP for PWID is an attractive option for HIV prevention, but robust implementation programs are necessary for roll-out. We still need to address upstream barriers to care for PWID, including stigma and health disparities. We need to continue to advocate for policy changes and funding for SSPs and OTPs to provide comprehensive HIV prevention.

Keywords: HIV; MOUD; PWID; PrEP; SSP; addiction; harm reduction.

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Abstract

Background

Although harm reduction is highlighted as an effective intervention for alcohol and drug use, a funding gap for harm reduction interventions has been identified, mainly in low- and middle-income countries. In these countries, tensions between abstinence and harm reduction models have impaired the shift from punitive practices to evidence-based interventions committed to guaranteeing the human rights of people who use drugs. Since 2015, the Brazilian government has adopted a more punitive and abstinence-focused drug policy that jeopardizes the care of people who use alcohol and other drugs and the comprehension of the harm reduction workers’ perspective in relation to their practice. Therefore, this study aimed to comprehend the meanings constructed by Brazilian harm reduction workers regarding their practices with vulnerable populations amidst a context of political tension.

Methods

We conducted 15 in-depth semi-structured qualitative interviews with harm reduction workers employed in public health services for at least 6 months. Data were analyzed using thematic analysis.

Results

The thematic axis “The joy and pain of being a harm reduction worker in Brazil” was constructed and divided into four major themes: (1) Invisibility of harm reduction work; (2) Black, poor, and people who use drugs: identification with the service users; (3) Between advocacy and profession: harm reduction as a political act; (4) Small achievements matter. Despite the perceived invisibility of harm reduction workers in the public health and alcohol and drug fields, valuing small achievements and advocacy were important resources to deal with political tension and punitive strategies in Brazil. The findings also highlight the important role of harm reduction workers due to their personal characteristics and understanding of drug use behavior, which bring the target audience closer to actions within the public health system.

Conclusion

There is an urgent need to acknowledge harm reduction based on peer support as a professional category that deserves adequate financial support and workplace benefits. Additionally, expanding evidence-based harm reduction interventions and community-based voluntary drug use treatment centers should be prioritized by public policies to address the human rights violations experienced by people who use drugs.

Keywords: Harm reduction work, Qualitative research, Social vulnerability, Substance use, Marginalization

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Abstract

Background:Men who have sex with men (MSM) in Brazil remain disproportionately affected by HIV. We estimated the potential incidence reduction by five years with increased uptake of publicly-funded, daily, oral tenofovir/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis (PrEP) among MSM using the Cost Effectiveness of Preventing AIDS Complications microsimulation model. We used national data, local studies, and literature to inform model parameters for three cities: Rio de Janeiro, Salvador, and Manaus.

Results: In Rio de Janeiro, a PrEP intervention achieving 10% uptake within 60 months would decrease incidence by 2.3% whereas achieving 60% uptake within 24 months would decrease incidence by 29.7%; results were similar for Salvador and Manaus. In sensitivity analyses, decreasing mean age at PrEP initiation from 33 to 21 years increased incidence reduction by 34%; a discontinuation rate of 25% per year decreased it by 12%.

Conclusion: Targeting PrEP to young MSM and minimizing discontinuation could substantially increase PrEP’s impact.

Keywords: Pre-exposure prophylaxis (PrEP), HIV prevention, Men who have sex with men, Modeling, Latin America and the Caribbean, Key and vulnerable populations.

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Abstract

Background: HIV infection is considered a public health problem. One of its coping strategies is the promotion of general knowledge about HIV and reduction of stigma related to the virus. However, little is known about these two constructs among people living with HIV (PLHIV).

Objective: To assess the levels of knowledge and stigma among PLHIV, and to examine the relationship between knowledge, stigma, and their associated factors.

Methods: A cross-sectional study was conducted from September 2022 to September 2023 at a Medication Dispensing Unit in Vitória, Brazil. Eligible PLHIV patients completed sociodemographic questionnaires and two instruments: the HIV Knowledge Questionnaire (HIV-K-Q, 43 items) and the Short HIV Stigma scale (12 items across four domains). Knowledge scores were based on correct answers, while stigma scores were calculated per domain, with higher scores indicating higher stigma. Statistical analyses included Student’s t-test and Pearson’s correlation (p ≤ 0.05). Ethical approval was obtained.

Results: Among 104 participants, 79.3% answered most HIV-K-Q items correctly, indicating high knowledge levels. Stigma was highest in the domains “Disclosure concerns” (mean 12, sd 0.84) and “Concerns with public attitudes” (mean 11, sd 0,57). No correlation was found between knowledge and stigma. Men and those with higher education scored higher in knowledge. Rural residents reported higher stigma in “Disclosure concerns”, and women showed higher stigma in “Concern with public attitudes”.

Conclusion: Participants demonstrated high HIV knowledge, but stigma levels were concerning, particularly in disclosure and public attitude domains. This suggests stigma may negatively impact PLHIV’s lives, highlighting the need for targeted interventions.

Keywords: AIDS; Attitudes and practice in health; HIV; Knowledge; Social stigma.

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Abstract

Background: Tele-harm reduction (THR) is a telehealth-enhanced, peer-led, harm reduction intervention delivered within a trusted syringe services program (SSP) venue. The primary goal of THR is to facilitate linkage to care and rapid, enduring virologic suppression among people who inject drugs (PWID) with HIV. An SSP in Miami, Florida, developed THR to circumvent pervasive stigma within the traditional healthcare system.

Methods: During intervention development, we conducted in-depth interviews with PWID with HIV (n = 25) to identify barriers and facilitators to care via THR. We employed a general inductive approach to transcripts guided by iterative readings of the raw data to derive the concepts, themes, and interpretations of the THR intervention.

Results: Of the 25 PWID interviewed, 15 were in HIV care and adherent to medication; 4 were in HIV care but non-adherent; and 6 were not in care. Themes that emerged from the qualitative analysis included the trust and confidence PWID have with SSP clinicians as opposed to professionals within the traditional healthcare system. Several barriers to treatment were reported among PWID, including perceived and actual discrimination by friends and family, negative internalized behaviors, denial of HIV status, and fear of engaging in care. Facilitators to HIV care included empathy and respect by SSP staff, flexibility of telehealth location, and an overall destigmatizing approach.

Conclusion: PWID identified barriers and facilitators to receipt of HIV care through the THR intervention. Interviews helped inform THR intervention development, centered on PWID in the destigmatizing environment of an SSP.

Keywords: HIV; Harm reduction; PWID; Stigma; Syringe services program; Tele-harm reduction.

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Abstract

Purpose of review: This review summarizes available data for lenacapavir (LEN), a first-in-class agent that targets several functions of the HIV capsid in the viral cycle, including nuclear entry, viral assembly, and capsid formation.

Recent findings: LEN has been approved in the United States as both oral tablets and injectable solution for treatment in heavily treatment-experienced adults with multidrug-resistant HIV-1. The subcutaneous injections are administered every 26 weeks (6 months). In 2024, LEN was named the biggest science breakthrough for HIV prevention and is currently under review at the FDA.

Summary: LEN is a novel agent that can be administered subcutaneously every 6 months. Approved for treatment-experienced adults with multidrug-resistant HIV, lenacapavir may have additional uses including for HIV prevention.

Keywords: capsid inhibitor; lenacapavir; long acting antiretroviral; multidrug-resistant HIV; preexposure prophylaxis.

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Abstract

Human immunodeficiency virus type 1 (HIV-1) remains a global health challenge, affecting over 38 million people as of 2024. The recent FDA approval of lenacapavir (Yeztugo®) on 18 June 2025 marks a significant advance in prevention and treatment. Lenacapavir is the first-in-class, long-acting HIV-1 capsid inhibitor, administered twice yearly via subcutaneous injection for pre-exposure prophylaxis in adults and adolescents ≥35 kg. It targets the capsid protein, disrupting multiple stages of the viral lifecycle without cross-resistance to existing antiretrovirals. Clinical trials (CAPELLA, CALIBRATE) demonstrated robust efficacy, with up to 94% viral suppression when combined with active agents and sustained CD4+ gains. Its prolonged half-life, minimal drug-drug interactions, and convenient dosing improve adherence, privacy, and healthcare access – critical in high-incidence, resource-limited settings. Ongoing PURPOSE trials are evaluating its role in high-risk populations. Lenacapavir’s favorable safety profile and public health potential support its integration into evolving HIV management and prevention strategies, potentially accelerating progress toward epidemic control.

Keywords: HIV-1; PrEP; capsid inhibitor; lenacapavir; long-acting therapy.

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Background: Major advances in antiretroviral therapy (ART) have transformed HIV into a chronic condition, yet drug resistance, long-term toxicities, adherence challenges, and persistent viral reservoirs continue to drive innovation. 

Objectives: To map and synthesize recent developments in anti-HIV drugs and delivery platforms with a focus on (i) new molecules in clinical development and (ii) novel mechanisms of action, following a scoping review framework aligned with PRISMA-ScR. Sources: We interrogated PubMed, Embase.com, Web of Science, and Scopus (January 2020-September 2025) and screened abstracts from CROI, IAS/AIDS, IDWeek, and HIV Glasgow (2023-2025). 

Content: The evidence base underscores capsid inhibition (lenacapavir) for multidrug-resistant HIV and its expansion into prevention, long-acting intramuscular maintenance with cabotegravir/rilpivirine, maturation inhibitors (zabofiravir), and attachment inhibition with fostemsavir. Broadly neutralizing antibodies (bNAbs) can sustain ART-free suppression in selected individuals. Ultra-long-acting delivery systems are advancing toward translational evaluation. 

Summary: The pipeline is diversifying toward less frequent dosing, new targets, and combination strategies. Successful and ethical implementation will require resistance-informed selection, equitable access, and reimagined healthcare delivery models that accommodate long-acting technologies.

Keywords: HIV; antiretroviral therapy; broadly neutralizing antibodies; capsid inhibitor; implants; long-acting therapy; maturation inhibitor; nanoparticles; prevention; scoping review. 

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Abstract

Background: Antiretroviral therapy (ART) has improved the clinical management of HIV-1 infection. However, little is known about how the latest ART recommendations affect the heterogeneity of the HIV-1 reservoir size. 

Methods: We used a complete statistical approach to outline parameters underlying the diversity in HIV-1 reservoir size in a cohort of 892 people with HIV-1 (PWH) on suppressive ART for more than 3 years. Total HIV-1-DNA levels were measured in PBMCs using digital droplet PCR (ddPCR).

Results: We classified 179 (20%) participants as being low viral reservoir treated (LoViReT) (<50 HIV-1-DNA copies/106 PBMCs). Twenty variables were collected to explore their association with the LoViReT phenotype using machine learning approaches. LoViReT status was closely associated with higher nadir CD4, lower zenith pre-ART viral load, lower CD4 recovery, shorter time from diagnosis to undetectable viral load, and initiation of treatment with an integrase inhibitor-containing (InSTI-containing) regimen. Initiation of ART with any InSTI was also linked with a shorter time to undetectable viremia. Locally estimated scatterplot smoothing (LOESS) regression revealed a progressive reduction in the size of the HIV-1 reservoir in individuals who started ART after 2007. Similarly, a higher nadir CD4 and a shorter time to undetectable viremia were observed when treatment was initiated after that year.

Conclusion: Our findings demonstrate that the progressive implementation of earlier, universal treatment at diagnosis and the use of InSTIs affected the size of the HIV-1 reservoir. Our work shows that effective management of infection is the first step toward reducing the reservoir and brings us closer to achieving a cure.

Keywords: AIDS/HIV; Drug therapy; Medical statistics; Molecular pathology; Virology.

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