Featured Literature
Preexposure Prophylaxis for HIV: Updated Recommendations from the 2024 International Antiviral Society-USA Panel. Available at: https://www.iasusa.org/2025/06/27/updated-recommendations-from-the-2024-international-antiviral-society-usa-panel/.
Interim Guideline on the Use of Twice-Yearly Lenacapavir for HIV Prevention: New York State Department of Health AIDS Institute Clinical Guidelines Program. Available at: https://www.hivguidelines.org/guideline/hiv-prep-len/?mycollection=pep-prep.
BASHH/BHIVA Guidelines on the Use of HIV Pre-exposure Prophylaxis (PrEP), 2025. Available at: https://bhiva.org/clinical-guideline/PrEP-guidelines/.
Guidelines on Lenacapavir for HIV Prevention and Testing Strategies for Long-acting Injectable Pre-exposure Prophylaxis (PrEP). Geneva: World Health Organization (WHO); 2025. Available at: https://www.who.int/publications/i/item/9789240111608.
Several groups (e.g., International Antiviral Society-USA, NYSDOH AIDS Institute, British Association for Sexual Health and HIV/British HIV Association, and World Health Organization) recently released updated PrEP recommendations. Although many of these were developed in response to the recent approval of lenacapavir, some also include newer data regarding oral PrEP. Of note, most groups recommend lab-based HIV antigen/antibody testing for lenacapavir initiation and continuation monitoring; WHO supports use of rapid diagnostic tests. HIV RNA (viral load) is not required but is recommended under certain circumstances, such as likely HIV exposure within the past 21 days, or concern for acute HIV in people not already taking and adherent to PrEP. Drug interaction potential should be carefully considered, since lenacapavir is a substrate and moderate inhibitor of CYP3A4 and a substrate of P-gp.
For people interested in oral PrEP options, IAS-USA now recommends TAF/FTC for prevention of HIV acquisition from vaginal exposures for people in whom TDF/FTC is contraindicated or undesirable. The BASHH/BHIVA updates outline several oral PrEP initiation and dosing strategies across multiple exposure types based on various PK/PD analyses and increasing confidence in recognizing PBMC drug levels as the relevant marker of protection. They also include sections on what to do in the event of missed doses, renal function assessment flowcharts, and suggestions for managing renal function changes while on PrEP.
Commentary
PrEP continues to be vastly underutilized in most communities – new products and innovative dosing strategies are greatly needed, and these updated guidelines will hopefully help address some outstanding questions and increase provider confidence and uptake across varied settings to increase PrEP access. Many clinical practices and HIV programs are likely adjusting their operations in anticipation of resource constraints, making simplification, integration, and task-shifting imperative as new PrEP options are implemented.
Featured Literature
Ring K, Elias A, Devonald M, Smuk M, Orkin C. Long-acting injectable cabotegravir and rilpivirine in observational cohort studies: a systematic review on virological failure, resistance and re-suppression outcomes in virally suppressed individuals living with HIV. HIV Med. 2025 Jun 13;1-22. doi:10.1111/hiv.70057.
The OUTCOMES Study is an evidence synthesis project involving ongoing systematic review of observational cohorts which describe virological outcomes among people transitioning to LA-CAB/RPV across different contexts (e.g., suppressed and non-suppressed). This article describes Phase 1 findings, which focused on people who are suppressed at time of LA-CAB/RPV initiation. Seventy-nine records met inclusion criteria for data extraction and analyses; for studies where virologic failure was not explicitly defined, investigators utilized another marker of VF (e.g., resistance or viral load exceeding a specified cut-off). Of the 79 studies, which comprised 13,899 individuals overall, 172 experienced VF events across 48 studies.
Genotypic data at VF were available for 28 studies, and out of the 80 VF events with available information, NNRTI DRMs were identified in 45 cases, INSTI DRMs in 40, and dual-class resistance in 33 (28 VF events had no evidence of resistance). The most prevalent NNRTI mutation was E138A/K (K101E/P/Q, K103K/R/N and Y181C/I were also noted), and the most prevalent INSTI mutations were Q148H/Q/K/R/S, E138A/E/K, G140G/S, L74L/M/I, T97T/A and R263K. Among 25 cohorts reporting post-VF regimens, PI-based combinations (31, 33.7%) were most commonly prescribed, followed by oral INSTI-based combinations (29, 31.5%). Twenty-seven percent (n=25) continued CAB/RPV after VF. Among 23 studies reporting re-suppression outcomes, re-suppression occurred in 87.8 percent (65/74).
Commentary
Despite heterogeneity in virologic failure definitions, HIVDR information at failure, post-VF ART management details and follow-up duration, this analysis provides some reassurance that VF has remained uncommon among virologically suppressed people switching to LA-CAB/RPV in routine practice. However, among people experiencing VF on LA-CAB/RPV, emergent NNRTI and/or INSTI resistance was observed in over half of cases with available information. Although PI-based regimens were most commonly used after VF, oral INSTI-based combinations were prescribed in almost a third of cases and LA-CAB/RPV was continued in over a quarter. Overall, the majority of people with VF on LA-CAB/RPV resuppressed, although it should be noted that follow-up duration varied widely, and almost all studies included were based in high-income countries.
Featured Literature
Han WM, Ryom L, Sabin CA, et al on behalf of the D:A:D and RESPOND Study Groups. Risk of cancer in people with HIV experiencing varying degrees of immune recovery with sustained virological suppression on antiretroviral treatment for more than 2 years: an international, multicentre, observational cohort. Clin Infect Dis. 2025 May 15: ciaf248. doi:10.1093/cid/ciaf248.
D:A:D and RESPOND collaborators combined longitudinal prospective data to assess whether poor immune recovery, despite virological suppression (VS) < 200 copies/mL, was independently predictive of cancer. Incident cases were centrally validated and reviewed by an external oncologist, and were grouped as AIDS-defining (ADC), non-AIDS-defining (NADC), infection-related, infection-unrelated, smoking-related, and/or obesity-related. Data from 48,343 participants achieving ≥ 2 years of VS were included: 74.4 percent were male, median age 43 years, median 7.4 years since HIV diagnosis, and median pre-ART CD4 nadir was 245 cells/µL.
Over 300,273 person years of follow-up, 3.9 percent of participants developed cancer corresponding to an overall incidence rate (IR) of 6.43/1000 PYFU. The most common were lung, anal, and prostate, followed by non-Hodgkin’s lymphoma and breast cancer. There were 258 ADC (0.5%) and 1675 NADC (3.5%) cases, corresponding to IRs of 0.86 and 5.58, respectively. There were 645 infection-related (IR 2.22) and 1,288 infection-unrelated (IR 4.29) cases reported. In multivariable analyses, higher time-updated CD4 was associated with a reduced risk of cancer development overall, with a linear trend by time-updated CD4 range: 350-499 cells/µL (aIRR 0.45), 500-749 cells/µL (aIRR 0.30), and ≥ 750 cells/µL (aIRR 0.26). Results were consistent for both ADC and NADC and for infection-related and unrelated cancers.
Commentary
Early and sustained antiretroviral therapy leading to durable virologic suppression remains the primary intervention for restoring immune function for people with HIV and reducing the development of certain cancers. However, D:A:D and RESPOND investigators observed that PWH with suboptimal immune recovery were still at increased risk of incident cancer across various categories despite ART-mediated virologic suppression. Authors highlight the ongoing importance of early screening/diagnosis with prompt ART initiation, as well as close attention to cancer screening especially for PWH with poor immune recovery.
Featured Literature
Reisner SL, Pletta DR, Mayer KH, et al. HIV seropositivity and viral non-suppression in transgender, non-binary, and gender-diverse people in primary care receiving gender-affirming hormone therapy in the USA between 2013 and 2019 (LEGACY): an observational, longitudinal, cohort study. Lancet HIV. 2025 Mar 17: S2352-3018(25)00004-9. doi:10.1016/S2352-3018(25)00004-9.
This analysis describes key HIV-related outcomes from the LEGACY study, which followed a diverse cohort of trans adults receiving primary care at two large, federally qualified health centers in the northeast U.S. Investigators assessed whether gender-affirming hormone therapy (GAHT) was associated with reduced rates of HIV seropositivity and viral non-suppression in the past 12 months. GAHT was delivered per established standards, and HIV testing was performed as clinically indicated per medical provider determination. De-identified health record data were extracted across seven years of follow-up.
Overall, rates of HIV seropositivity were 9.1 percent in 2013 and 6.9 percent in 2019, and viral non-suppression decreased: 22.4 percent of participants with HIV in 2013 were not suppressed compared to 15.7 percent in 2019. In multivariate analyses, participants with a current GAHT prescription had significantly lower risk of HIV seropositivity: factors associated with higher risk included being in an older age group; being a transgender woman or non-binary assigned male at birth; identifying as a racially or ethnically minoritized group; and having public or no insurance. Among participants with HIV, people with current GAHT prescription had significantly lower risk of viral non-suppression: associated factors included being in older age groups; being a transgender woman; and living at 100−199% FPL and 200–299% FPL (vs. 0–99% FPL).
Commentary
Gender-affirming hormone therapy can be effectively integrated within primary care settings, and results of this unique longitudinal study help affirm the role and necessity of gender-affirming hormone therapy (and low barrier access to such services) on key HIV outcomes, namely HIV seropositivity and viral non-suppression. Investigators highlight the importance of engagement in care to increase screening and identify new HIV infections among trans people and enhance viral suppression outcomes.
