Safety Assessment of Microbicide 2P23 on the Rectal and Vaginal Microbiota and Its Antiviral Activity on HIV Infection

Containment of the AIDS pandemic requires reducing HIV transmission. HIV infection is initiated by the fusion of the membrane between the virus and the cell membrane of the host. 2P23 is an effective HIV membrane fusion inhibitor that may be a good entry inhibitor microbicide candidate. This study evaluated the potential of using gel-formulated 2P23 as a topical microbicide to prevent sexual transmission of HIV in the rectum and vagina. Our data revealed that 2P23 formulated in gel is effective against HIV. There was no change in antiviral activity at 25°C for 4 months or 60°C for 1 week. In addition, we demonstrated that the 2P23 gel was stable and fully functional at pH 4.0–8.0 and under different concentrations of H2O2. Finally, the 2P23 gel exhibited no cytotoxicity or antimicrobial activity and did not induce inflammatory changes in the rectal or vaginal mucosal epithelium in New Zealand rabbits after 20 mg/day daily rectovaginal application for 14 consecutive days. Despite repeated tissue sampling and 2P23 gel treatment, the inflammatory cytokines and microbiota of the rectum and vagina remained stable. These results add to general knowledge on the in vivo evaluation of anti-HIV microbicide application concerning inflammatory cytokines and microbiota changes in the rectum and vagina. These findings suggest that the 2P23 gel is an excellent candidate for further development as a safe and effective pre-exposure prophylactic microbicide for the prevention of HIV transmission.

PSYCHOEDUCATION TO PREVENT THE SPREAD OF HIV AMONG MEN WHO HAVE SEX WITH MEN IN SURABAYA CITY

"Sexual transmission of HIV among Men who have Sex with Men (MSM) is believed to be one of the sources of the AIDS epidemic. Nowadays, governments, communities, and NGOs are taking action to prevent its spread by assisting and educating groups of MSM in their countries. This assistance involves experts in many fields of study, including psychology. In the field of psychology, psychoeducation is believed to be one of the ways to assist the MSM groups. In September to December 2019, the authors conducted a mentoring effort to the MSM community at the MSM community gathering location called Gang Pattaya, in the city of Surabaya, the second largest and densely populated city in Indonesia The existence of this community is disguised by the general public, but is well known by NGOs. Community members do MSM out of their liking, although some do it in exchange for money. However, safety factors, such as using condoms for MSM, are not a priority for this community. They do MSM whether they receive a reward or not, just out of a boost of pleasure. There is no attempt to find out the health of the partner once they are attracted to each other. In general, they do not know whether they are infected with HIV. Most of them feel healthy and since they do not show any symptoms, they think it is not necessary to get tested. In the mentoring process, we conduct psychoeducation, which begins with an approach to certain individuals so that they are comfortable with our presence, then increasing awareness of safer sex behavior for HIV prevention for groups in the form of counseling using the Theory of Reasoned Action (TRA) approach. Counseling is carried out in various forms including roleplay, games, and seminars. The number of participants was 11 people as agents of changes of the community, varying from 19 - 47 years old. Pretest related to knowledge of safer sex was carried out before conducting the intervention and post-test after the intervention. The normality test used is the Shapiro-Wilk analysis. Different tests on the data obtained were carried out using the non-parametric Wilcoxon Signed Ranks Test. None of the participants had lower post-test knowledge scores than the pre-test. Prestest and post test for safer sex behavior showed 2 participants with safer sex behavior did not change. Both belong to the senior group, while other participants have an improvement in their safer sex behavior. These findings suggest that intervention programs for MSM as an effort to reduce HIV transmission should pay attention to affective and cognitive coping strategies."

“Do I need to use condoms if I’m taking my meds?”

It has been conclusively proven that sexual transmission of HIV does not occur if the individual living with HIV is adherent to antiretroviral therapy and HIV replication is consistently maintained below a plasma level of 200 copies/mL. What remains to be defined is the frequency of viral load testing to provide assurance that HIV is suppressed and how long must it remain so until suppression can be considered durable. This is required in order to provide guidance for HIV pre-exposure prophylaxis (PrEP) use by a sexual partner who is not living with HIV. Based on currently published studies and until more data are presented, it seems prudent to recommend that sexual partners of individuals living with HIV who are highly adherent to treatment use PrEP for 6 months to 1 year following initiation of HIV treatment and that viral load testing be performed quarterly for at least the first 2 years in the partner living with HIV.

Amino Functionalized Micro-Mesoporous Hybrid Particles for the Sustained Release of the Antiretroviral Drug Tenofovir

The sustained release of an antiretroviral agent to women mucosa has been proved as an excellent strategy to reduce the sexual transmission of HIV. Hybrid micro-mesoporous particles have been synthesized and functionalized with a silane coupling agent followed by loading the antiretroviral tenofovir. It has been observed that the disposition of the silane molecule on the surface of the particles determines the interaction mechanism with the antiretroviral molecule loaded independently on the surface area of the particles. In this sense, available and free amino groups are required to achieve a smart pH-responsive material, a condition that is only achieved in those materials containing a silane chemisorbed monolayer. Moreover, the modulation of the release kinetics attributed to the presence of the silane monolayer covering the mesopores has been confirmed by fitting the releasing curves to the first order and Weibull models. The developed micro-mesoporous particles have been demonstrated to be excellent smart-release vehicles for antiviral agents and can be safely used in polymer mucoadhesive vaginal gels.

Acceptability of tenofovir gel as a vaginal microbicide among women in a phase I trial a mixed-methods study,

THE GLOBAL HIV EPIDEMIC increasingly affectswomen.1 For most, the only risk factor for becominginfected is the behavior of their male sexualpartners.1 Condoms often are unacceptableand insufficiently used,2–4 gender-based powerimbalances can make them difficult to negotiate,4–7 and religious beliefs, fertility needs, fear ofimplied infidelity, and preferences for sex withouta barrier are challenges to their acceptabilityand use. Women-initiated HIV prevention methodsare urgently needed, making the developmentof vaginal microbicides that reduce the likelihoodof sexual transmission of HIV a majorpublic health priority.First-generation vaginal microbicides will mostlikely be topical gels inserted into the vagina withan applicator. A variety of microbicides is currentlyunder development, and six have enteredlate-stage clinical trials.8–12 Initial product acceptabilityhas been assessed in clinical trials,13–16 surveysof product attributes among potentialusers17,18 and their partners,19 and studies that useover-the-counter (OTC) surrogates or placebo gelwith presumed similar formulation and applicationcharacteristics as eventual products.20–23 Acceptabilityassessments in early clinical trials areespecially important because their findings can influencefurther development of the product.Here, we report on acceptability data amongwomen participating in a phase I trial of tenofovirgel, a candidate microbicide that inhibits HIV reversetranscriptase. Details of the trial are reportedelsewhere,24 as is acceptability amongmale partners of trial participants.25 This was thefirst human trial of a topical antiretroviral thatspecifically inhibits a necessary replication stepin the HIV life cycle. Interest in this approach toHIV prevention has increased in recent yearssince efficacy trials of a topical surfactant(nonoxynyl-9) and a nonspecific inhibitor of HIVbinding (cellulose sulfate) indicated that thesetwo types of compounds were not protective andpotentially increased HIV transmission in womenwho had frequent sexual exposures to HIV. Severallarger-scale, expanded safety and proof-ofconcepttrials of tenofovir gel are now underway,based in part on the safety, tolerability, and acceptabilityof this microbicide demonstrated inthe study described in this paper.

The High Content of Fructose in Human Semen Competitively Inhibits Broad and Potent Antivirals That Target High-Mannose Glycans

ABSTRACT Semen is the primary transmission vehicle for various pathogenic viruses. Initial steps of transmission, including cell attachment and entry, likely occur in the presence of semen. However, the unstable nature of human seminal plasma and its toxic effects on cells in culture limit the ability to study in vitro virus infection and inhibition in this medium. We found that whole semen significantly reduces the potency of antibodies and microbicides that target glycans on the envelope glycoproteins (Envs) of HIV-1. The extraordinarily high concentration of the monosaccharide fructose in semen contributes significantly to the effect by competitively inhibiting the binding of ligands to α1,2-linked mannose residues on Env. Infection and inhibition in whole human seminal plasma are accurately mimicked by a stable synthetic simulant of seminal fluid that we formulated. Our findings indicate that, in addition to the protein content of biological secretions, their small-solute composition impacts the potency of antiviral microbicides and mucosal antibodies. IMPORTANCE Biological secretions allow viruses to spread between individuals. Each type of secretion has a unique composition of proteins, salts, and sugars, which can affect the infectivity potential of the virus and inhibition of this process. Here, we describe HIV-1 infection and inhibition in whole human seminal plasma and a synthetic simulant that we formulated. We discovered that the sugar fructose in semen decreases the activity of a broad and potent class of antiviral agents that target mannose sugars on the envelope protein of HIV-1. This effect of semen fructose likely reduces the efficacy of such inhibitors to prevent the sexual transmission of HIV-1. Our findings suggest that the preclinical evaluation of microbicides and vaccine-elicited antibodies will be improved by their in vitro assessment in synthetic formulations that simulate the effects of semen on HIV-1 infection and inhibition.

HIV infection among child population of the Republic of Bashkortostan

The aim of the study: to assess the incidence, prevalence, structure by sex and transmission routes of HIV infection among the child population of the Republic of Bashkortostan.A study of data on HIV infection among children 0—17 years in the republic for 2014—2018 was conducted.Results: the average incidence of HIV infection for 2014—2018 in the age group 0—14 years was 3.4 ± 0.4, 15—17 years — 8.7 ± 1.1, 0—17 years — 4.1 ± 0.4 per 100,000 child population of the corresponding age, the average prevalence of HIV infection at the age of 0—14 years — 26.6 ± 1.1, 15—17 years — 17.2 ± 3.1, 0—17 years — 25.2 ± 1.3 per 100,000 child population of the corresponding age. In 2018 compared to 2014 the incidence of HIV infection in the age group 0—14 years increased by 35.3%, 15—17 years — by 45.0%, 0—17 years — by 36.8%, the prevalence — in the age group 0—14 years increased by 27.4%, 15—17 years — 2.6 times, 0—17 years — by 38.3%. In 96.8% of HIV infections in children aged 0—14 years occurred as a result of perinatal transmission of the virus. Among children 0—14 years of age, 55.8% of cases were diagnosed with HIV infection at the age of 0—1 years. In 29.4% of children 0—14 years with perinatal transmission of HIV infection, the disease was detected at the age of 2 years and older. At the age of 15—17 years, sexual transmission of HIV infection prevailed — 90.9%, female adolescents accounted for 78.2%. In 21.8% of cases, HIV infection was detected in adolescents of the female sex during pregnancy follow-up, in 9.1% in the examination in connection with the consumption of drugs.