Comment

Pre-exposure prophylaxis for HIV prevention: how to predict success

One dramatic advance in human immunodeficiency virus (HIV) prevention efforts has been the prescription of medications typically used for HIV treatment as prophylaxis against acquiring HIV. As a preventative agent, this practice is referred to as “preexposure prophylaxis” (PrEP). The U.S. Federal Drug Administration approved daily PrEP for adults at risk for HIV who do not consistently use condoms during sex with HIV-infected or unknown-status partners. In this paper, we describe a cognitive-behavioral therapy (CBT) PrEP adherence intervention developed for use in high-risk sexual-minority men in the United States, adapted from “Life-Steps,” an evidence-based CBT intervention to promote adherence to HIV treatment. Modules include creating a PrEP dosing schedule, adhering to daily PrEP, problem solving barriers to adherence, and sexual risk-reduction techniques. Supplemented with practical video vignettes, this novel intervention may help to enhance the clinical practice of health care providers in outpatient settings to increase PrEP adherence in sexual-minority men.

HIV transmission in men who have sex with men (MSM) in the UK has shown no sign of decreasing in the past decade. Additional prevention measures are needed. We aimed to estimate the effect of various potential interventions implemented individually and in combination on prevention of HIV infection.

We extended a deterministic partnership-based mathematical model for HIV transmission, informed by detailed behavioural and surveillance data, to assess the effect of seven different HIV interventions implemented in MSM (aged 15–64 years) in the UK during 2014–20, including increasing rates of HIV testing, test-and-treat programmes, pre-exposure prophylaxis (PrEP), and sexual behavioural changes. We did sensitivity analyses on risk compensation.

We predicted a baseline of 16 955 new infections (IQR 13 156–21 669) in MSM in the UK during 2014–20. At a coverage of ≤50%, testing twice a year outperformed all other interventions. Of all intervention combinations, only the combined effect of test and treat and annual HIV testing (61·8%, IQR 47·2–81·8, of total incidence) was greater than the sum of effects of the two interventions individually (32·6%, 23·7–46·0, and 23·9%, 16·5–33·3, respectively). Simultaneous PrEP, expansion of HIV testing, and initiation of test-and-treat programme in 25% of high-activity MSM could save 7399 (IQR 5587–9813) UK MSM from HIV infection (43·6%, IQR 32·9–57·9, of total incidence). An increase in unsafe sex or sexual partners to 50% or more could substantially reduce the effect of interventions, but is unlikely to negate the prevention benefit completely.

PrEP could prevent a large number of new HIV infections if other key strategies including HIV testing and treatment are simultaneously expanded and improved. Without PrEP, HIV incidence in MSM in the UK is unlikely to decrease substantially by the end of this decade.

Health Protection Agency (now Public Health England).

3-Iodo-4-(2′-methylcyclohexyloxy)-6-phenethylpyridin-2(1H)-ones, as effective non-nucleoside reverse transcriptase inhibitors, were synthesized and resolved with different configurations. Biological results revealed that the trans-racemate 2b exhibited more potent activity than the cis-isomers. Noticeably, the trans-(S,S)-enantiomer 2e turned out to be significantly more potent than its counterpart enantiomer 2d against wild-type and double-mutant strains with high selectivity indexes.

The trans-(S, S)-enantiomer 2e turned out to be significantly more potent than its enantiomer 2d against wild-type and mutant strains with high selectivity indexes.

A novel 2-pyridinone scaffold was rationally designed and synthesized based on the active anti-HIV agent 1 (LAM-trans) via an efficient method. The biological results revealed that some target compounds inhibited HIV-1 reverse transcriptase in the lower micromolar concentration range (IC₅₀ 0.089–0.68 μm). Notably, the most promising compound 25b exhibited extremely potent inhibitory activity against HIV-1 replication with an EC₅₀ value of 0.0563 μM and the viral selectivity index amounted to 3466.8. Molecular modeling studies were performed, and some SARs were rationalized.

Pre-exposure prophylaxis (PrEP) has been considered as one of the promising interventions for HIV infection as experiments on various groups and sites have reported its significant effectiveness. This study evaluates the effectiveness of Tenofovir gel, one of the widely used PrEPs for women, through a mathematical model. Our model has excellent agreement with the experimental data on the use of Tenofovir gel as a PrEP in South African women. Using our model, we estimate both male-to-female and female-to-male transmission rates with and without Tenofovir gel protection. Through these estimates we demonstrate that the use of Tenofovir gel as a PrEP can significantly reduce the reproduction numbers, new infections, and HIV prevalence in South Africa. Our results further show that the effectiveness of Tenofovir gel largely depends on the level of adherence to the gel and the proportion of women under gel coverage. Even though Tenofovir gel alone may not be able to eradicate the disease as indicated by our estimates of the reproduction numbers, together with other interventions, such as condom use, it can serve as a strong weapon to fight against HIV epidemics.