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BackgroundHIV-1 set point viral load (SPVL) is a highly variable trait that influences disease progression and transmission risk. Men who are exclusively insertive (EI) during anal intercourse require more sexual contacts to become infected than exclusively receptive (ER) men. Thus, we hypothesize that EIs are more likely to acquire their viruses from highly infectious partners (i.e., with high SPVLs) and to have higher SPVLs than infected ERs.MethodsWe used a one-generation Bernoulli model, a dynamic network model, and data from the Multicenter AIDS Cohort Study (MACS) to examine whether and under what circumstances MSM differ in SPVL by sexual role.ResultsBoth models predicted higher SPVLs in EIs than role versatile (RV) or ER men, but only in scenarios where longer-term relationships predominated. ER and RV men displayed similar SPVLs. EI men remained far less likely than ER men to become infected, however. When the MACS data were limited by some estimates of lower sex partner counts (a proxy for longer relationships), EI men had higher SPVLs; these differences were clinically relevant (>0.3 log10 copies/mL) and statistically significant (p

: Introduction: Long‐acting injectable cabotegravir (CAB‐LA) demonstrated superiority to daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre‐exposure prophylaxis (PrEP) in the HPTN 083/084 trials. We compared the potential impact of expanding PrEP coverage by offering CAB‐LA to men who have sex with men (MSM) in Atlanta (US), Montreal (Canada) and the Netherlands, settings with different HIV epidemics. Methods: Three risk‐stratified HIV transmission models were independently parameterized and calibrated to local data. In Atlanta, Montreal and the Netherlands, the models, respectively, estimated mean TDF/FTC coverage starting at 29%, 7% and 4% in 2022, and projected HIV incidence per 100 person‐years (PY), respectively, decreasing from 2.06 to 1.62, 0.08 to 0.03 and 0.07 to 0.001 by 2042. Expansion of PrEP coverage was simulated by recruiting new CAB‐LA users and by switching different proportions of TDF/FTC users to CAB‐LA. Population effectiveness and efficiency of PrEP expansions were evaluated over 20 years in comparison to baseline scenarios with TDF/FTC only. Results: Increasing PrEP coverage by 11 percentage points (pp) from 29% to 40% by 2032 was expected to avert a median 36% of new HIV acquisitions in Atlanta. Substantially larger increases (by 33 or 26 pp) in PrEP coverage (to 40% or 30%) were needed to achieve comparable reductions in Montreal and the Netherlands, respectively. A median 17 additional PYs on PrEP were needed to prevent one acquisition in Atlanta with 40% PrEP coverage, compared to 1000+ in Montreal and 4000+ in the Netherlands. Reaching 50% PrEP coverage by 2032 by recruiting CAB‐LA users among PrEP‐eligible MSM could avert >45% of new HIV acquisitions in all settings. Achieving targeted coverage 5 years earlier increased the impact by 5–10 pp. In the Atlanta model, PrEP expansions achieving 40% and 50% coverage reduced differences in PrEP access between PrEP‐indicated White and Black MSM from 23 to 9 pp and 4 pp, respectively. Conclusions: Achieving high PrEP coverage by offering CAB‐LA can impact the HIV epidemic substantially if rolled out without delays. These PrEP expansions may be efficient in settings with high HIV incidence (like Atlanta) but not in settings with low HIV incidence (like Montreal and the Netherlands)., INTRODUCTION Two clinical studies (HPTN 083 and HPTN 084) have shown that long‐acting injectable cabotegravir (CAB‐LA) pre‐exposure prophylaxis (PrEP) given every 8 weeks is highly efficacious at preventing HIV among [...]

Pathogens face a tradeoff with respect to virulence; while more virulent strains often have higher per-contact transmission rates, they are also more likely to kill their hosts earlier. Because virulence is a heritable trait, there is concern that a disease-modifying vaccine, which reduces the disease severity of an infected vaccinee without changing the underlying pathogen genotype, may result in the evolution of higher pathogen virulence. We explored the potential for such virulence evolution with a disease-modifying HIV-1 vaccine in an agent-based stochastic epidemic model of HIV in United States men who have sex with men (MSM). In the model, vaccinated agents received no protection against infection, but experienced lower viral loads and slower disease progression. We compared the genotypic set point viral load (SPVL), a measure of HIV virulence, in populations given vaccines that varied in the degree of SPVL reduction they induce. Sensitivity analyses were conducted under varying vaccine coverage scenarios. With continual vaccination rollout under ideal circumstances of 90 % coverage over thirty years, the genotypic SPVL of vaccinated individuals evolved to become greater than the genotypic SPVL of unvaccinated individuals. This virulence evolution in turn diminished the public health benefit of the vaccine, and in some scenarios resulted in an accelerated epidemic. These findings demonstrate the complexity of viral evolution and have important implications for the design and development of HIV vaccines. [ABSTRACT FROM AUTHOR]

Background: Daily and on-demand pre-exposure prophylaxis (PrEP) are effective at preventing HIV acquisition among men who have sex with men (MSM), but only daily PrEP is approved in the US. On-demand PrEP may improve uptake and adherence. We identify sub-groups of MSM who would benefit from on-demand PrEP and determine effectiveness achieved if individuals used their optimal regimens., Methods: Using data from the HPTN 067 study (study period 2012-2014), we created an individual-based stochastic model of HIV risk in two synthetic MSM populations with parameters separately estimated using data from Harlem, US, and Bangkok, Thailand. Agents were assigned daily and on-demand PrEP for six months each. Two personalized PrEP assignments: optimal, based on improved predicted effectiveness and reduced pill burden, and adherence-based, using daily PrEP adherence, were simulated for another six months., Findings: Simulated on-demand PrEP was optimal for approximately one-third of MSM. It was assigned mainly to those with low daily PrEP adherence (88% (Harlem), 95% (Bangkok) of MSM with daily PrEP adherence <40%). Mean effectiveness was slightly higher in the full synthetic population with optimal PrEP assignment compared to universal daily PrEP. Among MSM for whom on-demand PrEP was optimal, mean effectiveness improved by 18 (Harlem) and 7 percentage points (Bangkok). Comparable predicted effectiveness was achieved if on-demand PrEP was assigned to the population with daily PrEP adherence <50%. There was no advantage in assigning on-demand PrEP by sex act frequency., Interpretation: On-demand PrEP could benefit many MSM by increasing effectiveness or decreasing pill burden with similar effectiveness. On-demand PrEP may be an effective alternative to daily PrEP for individuals with difficulty taking daily PrEP consistently. Results were similar for Harlem and Bangkok, indicating that these conclusions were robust in populations with different overall adherence levels and may inform future public-health policies., Funding: US NIH grant UM1 AI068617., Competing Interests: DJD declares support from the 10.13039/100000060National Institute for Allergy and Infectious Diseases (NIAID) and lecture honoraria from 10.13039/100006920University of Pennsylvania. MCB declares grants or contracts from MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the 10.13039/501100000265UK Medical Research Council (MRC) and the 10.13039/501100020171UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 program supported by the European Union. JH declares grants or contracts from the 10.13039/100000002National Institute of Health (NIH). The remaining authors declare no competing interests., (© 2022 The Author(s).)