Sexual Transmission Of Human Immunodeficiency Virus Research Articles

Prevention and infection control of HIV infection and AIDS

Background: Although the global incidence of human immunodeficiency virus (HIV) has decreased significantly since modern antiretroviral therapy (ART), new HIV infections steadily occur, in the Republic of Korea. Based on the understanding of the risk factors for HIV infection, combined strategic behavioral and biomedical interventions should be implemented to reduce HIV infection. This paper reviews the strategies for the prevention of HIV infection.Current Concepts: While the consistent use of latex condoms is effective for the prevention of HIV transmission, consistent use of condoms is low among sexually active individuals. ART can be initiated, after exposure, to prevent HIV infection (post-exposure prophylaxis) after occupational or sexual exposure, injection drug use, and other nonoccupational exposures to HIV. There is a negligible risk of sexual transmission of HIV when the HIV-infected sexual partner has durably suppressed viral replication with ART. Antiretroviral agents have been shown to be highly effective when administered prophylactically to HIV-uninfected but at-risk individuals (preexposure prophylaxis). A high-risk group, such as men who have sex with men, is required to be included in health insurance care benefits for pre-exposure prophylaxis, in addition to the current partners of HIV-infected individuals, to ensure its efficacy.Discussion and Conclusion: HIV-related deaths are rapidly decreasing, but new HIV infections continue to occur. In an environment where a cure or the development of vaccines is unlikely, a multifaceted and proactive approach is required to minimize new HIV infections.

Risk of sexual transmission of HIV in the context of viral load suppression.

In 2018, the Public Health Agency of Canada (PHAC) published a systematic review to calculate the risk of sexual transmission of human immunodeficiency virus (HIV) in the context of antiretroviral therapy (ART). In 2022, PHAC commissioned the Canadian Agency for Drugs and Technologies in Health (CADTH) to conduct a rapid review of evidence published since 2017. We undertook a meta-analysis of relevant studies from these two reviews. Studies from the rapid review that adequately assessed exposure (HIV viral load) and outcome (HIV seroconversion) were included and assessed for risk of bias (RoB) and certainty of evidence. Results were pooled to estimate the risk of HIV transmission per 100 person-years. Three studies from the rapid review were eligible for inclusion and one was excluded after RoB assessment. In the remaining studies examining risk among people living with HIV who take ART and maintain a suppressed viral load (fewer than 200 copies/mL, measured every 4-6 months), no sexual transmissions of HIV were observed. The pooled incidence estimate based on these studies, and one from the 2018 PHAC review, was zero transmissions/100 person-years (95% CI: 0.00-0.10). No studies in the rapid review provided data on the risk of sexual transmission of HIV in situations of varying levels of viral load. This update highlights the consistency of evidence since the 2018 PHAC review. There remains no evidence of HIV transmission to sexual partners when a person living with HIV is on ART and maintains a suppressed viral load.

Genetic network analysis of human immunodeficiency virus sexual transmission in rural Southwest China after the expansion of antiretroviral therapy: A population-based study.

This study is used to analyze the genetic network of HIV sexual transmission in rural areas of Southwest China after expanding antiretroviral therapy (ART) and to investigate the factors associated with HIV sexual transmission through the genetic network. This was a longitudinal genetic network study in Guangxi, China. The baseline survey and follow-up study were conducted among patients with HIV in 2015, and among those newly diagnosed from 2016 to 2018, respectively. A generalized estimating equation model was employed to explore the factors associated with HIV transmission through the genetic linkage between newly diagnosed patients with HIV (2016-2018) and those at baseline (2015-2017), respectively. Of 3,259 identified HIV patient sequences, 2,714 patients were at baseline, and 545 were newly diagnosed patients with HIV at follow-up. A total of 8,691 baseline objectives were observed by repeated measurement analysis. The prevention efficacy in HIV transmission for treated HIV patients was 33% [adjusted odds ratio (AOR): 0.67, 95% confidence interval (CI): 0.48-0.93]. Stratified analyses indicated the prevention efficacy in HIV transmission for treated HIV patients with a viral load (VL) of <50 copies/ml and those treated for 4 years with a VL of <50 copies/ml to be 41 [AOR: 0.59, 95% CI: 0.43-0.82] and 65% [AOR: 0.35, 95% CI: 0.24-0.50], respectively. No significant reduction in HIV transmission occurred among treated HIV patients with VL missing or treated HIV patients on dropout. Some factors were associated with HIV transmission, including over 50 years old, men, Zhuang and other nationalities, with less than secondary schooling, working as a farmer, and heterosexual transmission. This study reveals the role of ART in reducing HIV transmission, and those older male farmers with less than secondary schooling are at high risk of HIV infection at a population level. Improvements to ART efficacy for patients with HIV and precision intervention on high-risk individuals during the expansion of ART are urgently required.

Medical Care for Tuberculosis-HIV-Coinfected Patients in Russia with Respect to a Changeable Patients' Structure.

To date, tuberculosis (TB) remains the primary cause of mortality in human immunodeficiency virus (HIV) patients in Russia. Since the beginning of 2000, a sharp change in the HIV patients’ structure, to the main known risk factors for HIV infection has taken place in Russia. The transmission of HIV through injectable drug use has begun to decline significantly, giving way to the prevalence of sexual HIV transmission today. These changes may require adjustments to organizational approaches to anti-TB care and the treatment of HIV-positive patients. Our study is aimed at identifying changes in TB-HIV coinfection patients’ structures in 2019 compared to 2000. Based on the results obtained, our goal was to point out the parameters that need to be taken into account when developing approaches to improve the organization of TB control care for people with HIV infection. We have carried out a cross-sectional, retrospective, epidemiological study using government TB registry data from four regions in two federal districts of Russia in 2019. The case histories of 2265 patients from two regions with high HIV prevalence, which are part of the Siberian Federal District of Russia, and 89 patient histories from two regions of low HIV prevalence, which are part of the Central Federal District of Russia, were analyzed. We found that parenteral transmission (69.4%) remains the primary route of HIV transmission among the TB-HIV coinfected. The unemployed of working age without disability account for 80.2% of all coinfected people, while the formerly incarcerated account for 53.7% and the homeless account for 4.1%. Those with primary multidrug-resistant TB (MDR-TB) comprise 56.2% of HIV-TB patients. When comparing the incidence of coinfection with HIV among TB patients, statistically significant differences were obtained. Thus, the chances of coinfection increased by 4.33 times among people with active TB (95% CI: 2.31; 8.12), by 2.97 times among people with MDR-TB (95% CI: 1.66; 5.32), by 5.2 times in people with advanced processes in the lungs, including destruction, (95% CI: 2.78; 9.7), as well as by 10.3 times in the case of death within the first year after the TB diagnosis (95% CI: 2.99; 35.5). The absence of data for the presence of TB during preventive examination was accompanied by a decrease in the chances of detecting coinfection (OR 0.36; 95% CI: 0.2; 0.64). We have identified the probable causes of the high incidence of TB among HIV-infected: HIV-patient social maladaptation usually results in delayed medical care, leading to TB treatment regimen violations. Furthermore, self-administration of drugs triggers MDR-TB within this group. Healthcare providers should clearly explain to patients the critical importance of immediately seeking medical care when initial TB symptoms appear.

Preventing the sexual transmission of HIV

There are a number of measures that are available to reduce the sexual transmission and acquisition of the human immunodeficiency virus (HIV). These include: antiretroviral (ARV) therapy in those living with HIV to achieve an undetectable viral load, which eliminates the sexual transmission of HIV, and is a concept known as ‘Undetectable = Untransmittable’ (‘U=U’); Pre-Exposure Prophylaxis (PrEP) and Post-Exposure Prophylaxis (PEP) to HIV, which provide protection against the sexual acquisition of HIV; and advice for HIV-negative women who wish to conceive with a male partner living with HIV.

Development of pH-sensitive vaginal films based on methacrylate copolymers for topical HIV-1 pre-exposure prophylaxis

Interest is growing in “smart” vaginal microbicides as a strategy to protect women from sexual transmission of human immunodeficiency virus (HIV). The concept is based on the development of products featuring low drug release in acidic media such as vaginal fluid but switch to a fast release profile when the medium becomes neutral or slightly alkaline. This mimics the surge in pH occurring in the vagina after sexual intercourse due to the seminal fluid. Semen is the main vehicle for HIV-1, and increasing antiretroviral drug levels in the vagina upon ejaculation may contribute to enhanced protection against viral sexual transmission. This work explores the use of different pharmaceutical-grade methacrylic acid-based polymers (EudragitⓇ RL, RS, L and S) for developing vaginal films allowing the pH-dependant release of the antiretroviral drug tenofovir (TFV). EudragitⓇ L 100 and EudragitⓇ S 100, containing triethyl citrate as plasticiser, proved to be suitable for manufacturing films with optimal dual in vitro drug-release behaviour. TFV-release can be sustained for several days after film administration and all the drug is released in a few hours in conditions simulating ejaculation. The films’ mechanical properties were also deemed suitable for comfortable vaginal administration. Two optimized films were further assessed using HEC-1-A and Ca Ski cell monolayer models and were found to possess favourable drug permeability profiles and drug levels associated to cell monolayer as compared to free TFV. Overall, pH-dependant films containing tenofovir may constitute promising candidates for “smart” vaginal microbicides to protect women from sexual HIV transmission.

Advances and challenges in antiretroviral therapy for acquired immunodeficiency syndrome.

Advances and challenges in antiretroviral therapy for acquired immunodeficiency syndrome.

Towards evidence-based integration of services for HIV, non-communicable diseases and substance use: insights from modelling.

Towards evidence-based integration of services for HIV, non-communicable diseases and substance use: insights from modelling.

Mucoadhesive Vaginal Discs based on Cyclodextrin and Surfactants for the Controlled Release of Antiretroviral Drugs to Prevent the Sexual Transmission of HIV.

The strategies for developing vaginal microbicides to protect women against human immunodeficiency virus (HIV) sexual transmission are constantly changing. Although the initial dosage forms required daily administration to offer effective protection, the trend then moved towards sustained-release dosage forms that require less frequency of administration in order to improve women’s compliance with the treatment. Nevertheless, another possible strategy is to design on-demand products that can be used in a coitally-dependent manner and only need to be administered immediately before intercourse to offer protection. Vaginal discs based on freeze-dried hydroxypropylmethyl cellulose gels have been developed for this purpose, containing two surfactants, i.e., sodium dodecyl sulphate and polysorbate 60, alone or in combination with 2-hydroxypropyl-β-cyclodextrin, to achieve a formulation capable of incorporating both hydrophilic and lipophilic drugs. Several studies have been carried out to evaluate how the inclusion of these substances modifies the structure of gels (viscosity and consistency studies) and the porosimetry of the freeze-dried discs (scanning electron microscopy micrographs, mechanical properties, swelling behaviour). The drug release and mucoadhesive properties of the discs have also been evaluated with a view to their clinical application. The systems combining sodium dodecyl sulphate and 2-hydroxypropyl-β-cyclodextrin were found to be adequate for the vaginal administration of both Tenofovir and Dapivirine and also offer excellent mucoadhesion to vaginal tissue; these discs could therefore be an interesting option for a coitally-dependent administration to protect women against HIV transmission.

Cytokine Network and Sexual Human Immunodeficiency Virus Transmission in Men Who Have Sex With Men.

Seminal human immunodeficiency virus (HIV) transmission from men to their partners remains the main driver of HIV epidemics worldwide. Semen is not merely a carrier of the virus, but also provides an immunological milieu that affects HIV transmission. We collected blood and semen from people with HIV whose epidemiologically linked sexual partners either did or did not acquire HIV. Viral transmission was confirmed by phylogenetic linkage (HIV pol). We measured the concentration of 34 cytokines/chemokines by Luminex in the blood and semen of 21 source partners who transmitted HIV (transmitters) and 22 who did not transmit HIV (nontransmitters) to their sexual partners. Differences between cytokine profiles in transmitters versus nontransmitters were analyzed using the multivariate statistical technique of partial least square discriminant analysis. The cytokine profile in seminal fluid, but not in peripheral blood, was significantly different between men who have sex with men (MSM) who transmitted HIV and those who did not transmit HIV to their sexual partners (E = 19.77; P < .01). This difference persisted after excluding people with undetectable HIV RNA levels in nontransmitters. Seminal cytokine profiles correlated with transmission or nontransmission of HIV from the infected MSM to their partners, independently from seminal viral load. Seminal cytokine spectra might be a contributing determinant of sexual HIV transmission, thus providing new directions for the development of strategies aimed at preventing HIV transmission.

Knowledge and sexual behaviors of transgender individuals faced with the risk of STI/HIV in Benin

Abstract Introduction The issue of sexually transmitted infections (STIs) and Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) cannot be solved without considering the transgender population. This research aims to describe the knowledge, attitudes and sexual behaviors of transgender individuals faced with the risk of STIs and HIV/AIDS in Benin. Methods Transgender individuals were selected by respondent-driven sampling throughout the country in 2017. Included in this analysis were individuals who identified as transgender and adopted its mode of expression, aged 15 years and greater, and who gave their consent to participate. Results A total of 308 transgender individuals were surveyed, of which 89.6% were of male gender at birth. The participants had a good level of knowledge in the matter of STI and HIV/AIDS. In fact, 99.9% among them cited at least one symptom of STIs; 95.1% cited the three main methods of transmission of HIV and 54% are aware the risk of sexual transmission of HIV is higher between men. Participants were more than 90% likely to declare a positive attitude to care for persons living with HIV (PLWHIV) or to share the same room with them (93.2%). Concerning sexual behaviors, the average age at the first sexual encounter as a transgender individual was 14 years old. During the last three months, transgender individuals declared three regular male partners on average. The usage of condoms during the last sexual intercourse was reported in 86.6% of cases. Knowledge of the serological status of the sexual partner (31.7%) and the loss of sensation induced by the condom (26.8%) constituted the main reasons of non-usage of condoms. Conclusions Although adopting some risky sexual behavior, transgender individuals are a population that is relatively well informed and with favorable attitudes regarding STIs and HIV/AIDS. These factors are significant assets to be considered in the development of programs for STIs and HIV/AIDS control. Key messages Transgender individuals good level of knowledge is an asset for STIs/HIV control. Sexual multi-partnership seems to be common despite a good level of knowledge.

A unique class of lignin derivatives displays broad anti-HIV activity by interacting with the viral envelope

In Gordts et al. (2015), we have shown that lignosulfonic acid, a commercially available lignin derivative, possesses broad antiviral activity against human immunodeficiency virus (HIV) and Herpes simplex virus (HSV) by preventing viral entry into susceptible target cells. Because of the interesting safety profile as potential microbicide, we now determined the antiviral activity of a series of lignosulfonates in order to understand better which molecular features can contribute to their antiviral activity. Here, 24 structurally different lignosulfonates were evaluated for their capacity to inhibit HIV and HSV transmission and replication in various cellular assays. These derivatives differ in origin (hardwood or softwood), counter-ion used during sulphite processing (Na+, Ca2+, or NH4+), sulphur content, carboxylic acid percentage, and molecular weight fraction, which allowed to determine structure-activity relationships. We demonstrate that the broad antiviral activity of lignosulfonates is mainly dependent on their molecular weight and that their mechanism of action is based on interactions with the viral envelope glycoproteins. This makes the lignosulfonates a potential low-cost microbicide that protects women from sexual HIV and HSV transmission and thus prevents life-long infection.

Trends in Sexual Risk Behaviors Among Hispanic/Latino Men Who Have Sex with Men - 19 Urban Areas, 2011-2017.

Correct and consistent condom use and human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) are protective against sexual transmission of HIV (1,2). The incidence of HIV infection among Hispanic/Latino men who have sex with men (MSM) in the United States is increasing (3). HIV risk among Hispanic/Latino MSM differs based on their place of birth and years of U.S. residence (4). Data from CDC's National HIV Behavioral Surveillance (NHBS)* for 2011-2017 were analyzed to assess changes in sexual risk behaviors among Hispanic/Latino MSM by place of birth and years of U.S. residence. Overall, condomless anal sex during the previous 12 months increased from 63% in 2011 to 74% in 2017, and PrEP use during the previous 12 months increased from 3% in 2014 to 24% in 2017. Regardless of place of birth, nearly 75% of Hispanic/Latino MSM reported condomless anal sex during 2017. However, because of PrEP use, <60% of non-U.S.-born Hispanic/Latino MSM and <50% of U.S.-born Hispanic/Latino MSM reported unprotected anal sex (condomless anal sex and no PrEP use) during 2017. Results indicate that PrEP can be a vital tool for reducing HIV transmission among Hispanic/Latino MSM, especially those who have condomless anal sex. Interventions to prevent HIV acquisition, including increasing PrEP uptake, could address cultural and linguistic needs of Hispanic/Latino MSM, as well as other barriers to prevention of HIV infection typically faced by all MSM.

Smart Freeze-Dried Bigels for the Prevention of the Sexual Transmission of HIV by Accelerating the Vaginal Release of Tenofovir during Intercourse.

Sub-Saharan African women are still at risk from the human immunodeficiency virus (HIV), and sex with men is the main route of transmission. Vaginal formulations containing antiretroviral drugs are promising tools to give women the power to protect themselves. The aim of this work was to obtain freeze-dried bigels containing pectin, chitosan, or hypromellose for the vaginal controlled release of Tenofovir, which is accelerated in the presence of semen. Nine batches of bigels were formulated using different proportions of these polymers in the hydrogel (1, 2, and 3% w/w). The bigels obtained were freeze-dried and then underwent hardness and deformability, mucoadhesion, swelling, and drug release tests, the last two in simulated vaginal fluid (SVF) and SVF/simulated seminal fluid (SSF) mixture. The formulation containing 3% pectin (fd3P) has the highest values for hardness, resistance to deformation, and good mucoadhesivity. Its swelling is conditioned by the pH of the medium, which is responsive to the controlled release of Tenofovir in SVF, with the fastest release in the SVF/SSF mixture. fd3P would be an interesting smart microbicidal system to allow faster release of Tenofovir in the presence of semen, and thus increase women’s ability to protect themselves from the sexual transmission of HIV.

Siyaphambili protocol: An evaluation of randomized, nurse-led adaptive HIV treatment interventions for cisgender female sex workers living with HIV in Durban, South Africa.

In South Africa, 60% of female sex workers are estimated to be living with human immunodeficiency virus (HIV). Many of these women face structural and individual-level barriers to initiating, accessing, and adhering to antiretroviral therapy (ART). While data are limited, it is estimated that less than 40% of sex workers living with HIV achieve viral suppression, leading to suboptimal clinical outcomes and sustained risks of onward sexual and vertical HIV transmission. Siyaphambili, a NINR/NIH-funded study, focuses on studying optimal implementation strategies for meeting HIV treatment needs among cisgender female sex workers living with HIV who are not virally suppressed. Here, we present the study protocol of this sequential multiple assignment randomized trial. In total, 800 viremic female sex workers will be enrolled into an 18-month adaptive implementation study to 1) compare the effectiveness and durability of a nurse-led decentralized ART treatment program versus an individualized case management approach, in isolation or in combination to achieve viral suppression and 2) estimate incremental cost-effectiveness of interventions and combinations of interventions. The primary outcome is a combined intention-to-treat outcome of retention in ART care and viral suppression at 18 months with secondary implementation outcomes. Siyaphambili aims to inform the implementation of and scale-up of HIV treatment services for female sex workers by determining the minimal package of services needed to achieve viral suppression and by characterizing individuals in need of more intensive HIV treatment approaches.

Factors Associated With Discussions of Human Immunodeficiency Virus Pre-Exposure Prophylaxis in Men Who Have Sex With Men.

Background: Pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (Truvada) is highly effective at preventing human immunodeficiency virus (HIV) transmission in high-risk populations, including in men who have sex with men (MSM). In 2019, the US Preventive Services Task Force released an A recommendation to offer PrEP to persons at high risk of HIV acquisition. Despite the demonstrated efficacy of PrEP, areas with high HIV incidence, such as Louisiana, have historically had low PrEP prescription rates. The objective of this study was to determine the factors associated with whether providers in the Ochsner Health System (OHS) discussed PrEP with HIV-negative MSM patients. Methods: Investigators extracted electronic medical record data on all HIV-negative MSM patients who had at least one outpatient visit at OHS between July 1, 2012 and July 1, 2016 and manually reviewed a random sample of 115 charts. Results: Subjects were predominantly Caucasian (75.7%) with a mean age of 37.6 years. A PrEP discussion was documented for 34 (29.6%) patients. Multivariate modeling showed that having a PrEP discussion was associated with 3 factors: being assigned to a primary care provider known to specialize in MSM care (odds ratio [OR] 5.05, 95% confidence interval [CI] 1.81-14.10; P=0.002), having a documented history (positive or negative) of sexually transmitted infection vs no documentation (OR 5.41, 95% CI 1.80-16.23; P=0.003), and having documentation of condom use (consistent or inconsistent) vs no documentation (OR 3.32, 95% CI 1.27-8.74; P=0.015). Conclusion: Despite evidence that PrEP significantly reduces sexual transmission of HIV in MSM, PrEP discussions with MSM across OHS were undesirably low. Additional resources need to be aimed at increasing PrEP uptake and should focus on providing skills-based training and education in PrEP and MSM care to healthcare providers. With increased knowledge of and familiarity with PrEP prescribing guidelines, more providers will be better equipped to identify at-risk patients and to discuss prevention options such as PrEP.

Freeze-dried bioadhesive vaginal bigels for controlled release of Tenofovir

Nowadays, million women live with the human immunodeficiency virus (HIV) worldwide and many of them are dying per year, particularly in Sub-Saharan Africa. The development of systems that can be accessed by this population group to prevent the sexual transmission of the virus is therefore necessary. The aim of this work was the formulation of freeze-dried bioadhesive vaginal bigels releasing Tenofovir in a controlled manner. Systems containing three different proportions of guar gum hydrogel and sesame oil were prepared, adding Span®60 or Span®60 and Tween®60 as surfactants. Drug and excipients were evaluated by cytotoxicity assays, showing no toxicity at the concentrations tested neither for the drug nor any of the excipients. Fresh formulations were characterised through texture analyses and confocal laser microcopy. The system with the lowest guar gum hydrogel/sesame oil proportion and containing Span®60 and Tween®60 (batch ST1) had the highest consistency and adhesion capacity according to texture analyses. Furthermore, a genuine bigel microstructure was observed. After freeze-drying, swelling, bioadhesion and drug release tests were performed on the resulting systems. ST1 showed the longest bioadhesion time and the most controlled release, as well as a low swelling grade, becoming an interesting option for preventing HIV sexual transmission in women.

Condylomata Acuminata (Anogenital Warts) Contain Accumulations of HIV-1 Target Cells That May Provide Portals for HIV Transmission.

Condylomata acuminata (anogenital warts [AGWs]) are prevalent in human immunodeficiency virus (HIV)-infected individuals and sexually active populations at risk for HIV acquisition and have been associated with HIV transmission. We compared AGW specimens to control tissue specimens for abundance, types, and location of HIV target cells and for susceptibility to HIV infection in vitro, to provide biologic evidence that AGWs facilitate HIV transmission. We used immunohistologic staining to identify HIV target cells in AGW and control specimens. We also inoculated HIV in vitro into AGW and control specimens from HIV-negative men and assessed infection by means of TZM-bl and p24 assays. CD1a+ dendritic cells, CD4+ T cells, and macrophages were significantly more abundant in the epidermis of AGW specimens than control specimens. These HIV target cells also often appeared in large focal accumulations in the dermis of AGW specimens. Two of 8 AGW specimens versus 0 of 8 control specimens showed robust infection with HIV in vitro. Compared with normal skin, AGWs contain significantly higher concentrations of HIV target cells that may be susceptible to HIV infection. Condylomata may thus promote HIV transmission, especially in the setting of typical lesion vascularity and friability. Prevention or treatment of AGWs may decrease the sexual transmission of HIV.

Myricetin antagonizes semen-derived enhancer of viral infection (SEVI) formation and influences its infection-enhancing activity

BackgroundSemen is a critical vector for human immunodeficiency virus (HIV) sexual transmission and harbors seminal amyloid fibrils that can markedly enhance HIV infection. Semen-derived enhancer of viral infection (SEVI) is one of the best-characterized seminal amyloid fibrils. Due to their highly cationic properties, SEVI fibrils can capture HIV virions, increase viral attachment to target cells, and augment viral fusion. Some studies have reported that myricetin antagonizes amyloid β-protein (Aβ) formation; myricetin also displays strong anti-HIV activity in vitro.ResultsHere, we report that myricetin inhibits the formation of SEVI fibrils by binding to the amyloidogenic region of the SEVI precursor peptide (PAP248–286) and disrupting PAP248–286 oligomerization. In addition, myricetin was found to remodel preformed SEVI fibrils and to influence the activity of SEVI in promoting HIV-1 infection. Moreover, myricetin showed synergistic effects against HIV-1 infection in combination with other antiretroviral drugs in semen.ConclusionsIncorporation of myricetin into a combination bifunctional microbicide with both anti-SEVI and anti-HIV activities is a highly promising approach to preventing sexual transmission of HIV.

Chloro-1,4-dimethyl-9H-carbazole Derivatives Displaying Anti-HIV Activity.

Background: Despite the progress achieved by anti-retroviral drug research in the last decades, the discovery of novel compounds endowed with selective antiviral activity and reduced side effects is still a necessity. At present, the most urgent requirement includes the improvement of HIV (Human Immunodeficiency Virus) prevention and sexual transmission and the development of new drugs to treat the chronic lifelong infection. Methods: Six chloro-1,4-dimethyl-9H-carbazoles (2a,b–4a,b) have been prepared following opportunely modified known chemical procedures and tested in luciferase and Escherichia coli β-galactosidase expressing CD4+, CXCR4+, CCR5+ TZM-bl cells. Results and Conclusion: a preliminary biological investigation on the synthesized small series of chloro-1,4-dimethyl-9H-carbazoles has been carried out. Among all tested compounds, a nitro-derivative (3b) showed the most interesting profile representing a suitable lead for the development of novel anti-HIV drugs.