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Countering the rise of syphilis: A role for doxycycline post-exposure prophylaxis?

ABSTRACT: Doxycycline post-exposure prophylaxis (PEP) holds the potential to mitigate increasing rates of syphilis among sexual minority men (SMM) in the US yet has received limited attention. Since evaluation of this intervention in actual populations is not currently feasible, we used agent-based models (ABM) to assess the population-level impact of this strategy. We adapted ABM of HIV and HPV transmission, representing a population of 10,230 SMM in Philadelphia, Pennsylvania, US. Parameter inputs were derived from the literature, and ABM outputs during the pre-intervention period were calibrated to local surveillance data. Intervention scenarios varied doxycycline uptake by 20, 40, 60, 80 and 100%, while assuming continued condom use and syphilis screening and treatment. Under each intervention scenario, we incorporated treatment adherence at the following levels: 0, 20, 40, 60, 80 and 100%. Long-term population impact of prophylactic doxycycline was measured using the cumulative incidence over the 10-year period and the percentage of infections prevented attributable to doxycycline at year 10. An uptake scenario of 20% with an adherence level of 80% would reduce the cumulative incidence of infections by 10% over the next decade, translating to 57 fewer cases per 1000 SMM. At year 10, under the same uptake and adherence level, 22% of infections would be prevented due to doxycycline PEP in the instances where condoms were not used or failed. Findings suggest that doxycycline PEP will have a modest impact on syphilis incidence when assuming a reasonable level of uptake and adherence. Doxycycline PEP may be most appropriate as a secondary prevention measure to condoms and enhanced syphilis screening for reducing infections among SMM.

SUBMITTER: Tran NK

PROVIDER: S-EPMC8688295 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:With the rise of the second pandemic wave of the novel influenza A (H1N1) virus in the current season in the Northern Hemisphere, pandemic plans are being carefully re-evaluated, particularly for the strategic use of antiviral drugs. The recent emergence of oseltamivir-resistant in treated H1N1 patients has raised concerns about the prudent use of neuraminidase inhibitors for both treatment of ill individuals and post-exposure prophylaxis of close contacts.We extended an established population dynamical model of pandemic influenza with treatment to include post-exposure prophylaxis of close contacts. Using parameter estimates published in the literature, we simulated the model to evaluate the combined effect of treatment and prophylaxis in minimizing morbidity and mortality of pandemic infections in the context of transmissible drug resistance.We demonstrated that, when transmissible resistant strains are present, post-exposure prophylaxis can promote the spread of resistance, especially when combined with aggressive treatment. For a given treatment level, there is an optimal coverage of prophylaxis that minimizes the total number of infections (final size) and this coverage decreases as a higher proportion of infected individuals are treated. We found that, when treatment is maintained at intermediate levels, limited post-exposure prophylaxis provides an optimal strategy for reducing the final size of the pandemic while minimizing the total number of deaths. We tested our results by performing a sensitivity analysis over a range of key model parameters and observed that the incidence of infection depends strongly on the transmission fitness of resistant strains.Our findings suggest that, in the presence of transmissible drug resistance, strategies that prioritize the treatment of only ill individuals, rather than the prophylaxis of those suspected of being exposed, are most effective in reducing the morbidity and mortality of the pandemic. The impact of post-exposure prophylaxis depends critically on the treatment level and the transmissibility of resistant strains and, therefore, enhanced surveillance and clinical monitoring for resistant mutants constitutes a key component of any comprehensive plan for antiviral drug use during an influenza pandemic.

Project description:OBJECTIVES:In British Columbia, Canada, syphilis is at record-high rates, with over 80% of cases in 2017 seen in gay, bisexual and other men who have sex with men (GBM). The syphilis epidemic is of particular concern for those living with HIV, since syphilis may lead to more serious complications in this population. We sought to explore syphilis-related knowledge and attitudes around biomedical prevention options for syphilis, with the goal of informing effective strategies to prevent syphilis. DESIGN:We conducted a qualitative study consisting of in-depth, individual interviews from December 2016 to June 2017. Our interviews focused on participants' knowledge about syphilis and perceptions regarding syphilis pre-exposure prophylaxis (PrEP). Interviews were analysed using Grounded Theory. PARTICIPANTS:Twenty-five GBM were interviewed (64% white; median age: 43 years), including men living with HIV and/or with a history of syphilis. SETTING:Vancouver, British Columbia. RESULTS:Five interrelated themes emerged. First, GBM were aware of the local syphilis epidemic. Second, syphilis-related knowledge differed according to syphilis and HIV serostatus. Third, competing ideas emerged regarding men's concerns about syphilis. While our participants expressed concern about getting syphilis, they also described the importance of sexual pleasure. Fourth, many participants said that syphilis was not perceived to be alarming; preventing HIV infection remained a primary concern for many. Finally, while syphilis PrEP was appealing to those living with HIV or a prior syphilis diagnosis, others were concerned about antibiotic resistance, cost and side effects. CONCLUSIONS:Our participants organised their safer sex strategies around HIV, not syphilis. Although syphilis-related knowledge was relatively high among GBM living with HIV and those with a prior syphilis diagnosis, this knowledge did not appear to be related with safer sexual practices, such as increased condom use. This work highlights the importance of examining other potential prevention solutions, such as syphilis PrEP.

Project description:ObjectivesSexual assault (SA) is recognized as a public health problem of epidemic proportions. Guidelines recommend the administration of post-exposure prophylaxis (PEP) after an SA. However, few data are available about the feasibility of this strategy, and this study was conducted to assess this.MethodsWe conducted a retrospective, longitudinal, observational study in SA victims attending the Hospital Clinic in Barcelona from 2006 to 2015. A total of 1695 SA victims attended the emergency room (ER), of whom 883 met the PEP criteria. Five follow-up visits were scheduled at days 1, 10, 28, 90 and 180 in the out-patient clinic. The primary endpoint was PEP completion rate at day 28. Secondary endpoints were loss to follow-up, treatment discontinuation, occurrence of adverse events (AEs) and rate of seroconversion.ResultsThe median age of participants was 25 years [interquartile range (IQR) 21-33 years] and 93% were female. The median interval between exposure and presentation at the ER was 13 h (IQR 6-24 h). The level of risk was appreciable in 47% (n = 466) of individuals. Of 883 patients receiving PEP, 631 lived in Catalonia. In this group, the PEP completion rate at day 28 was 29% (n = 183). The follow-up rate was 63% (n = 400) and 38% (n = 241) at days 1 and 28, respectively. Treatment discontinuation was present in 58 (15%) of 400 patients who attended at least the day 1 visit, the main reason being AEs (n = 35; 60%). AEs were reported in 226 (56%) patients, and were mainly gastrointestinal (n = 196; 49%). Only 211 (33%) patients returned for HIV testing at day 90. A single seroconversion was observed in a men who have sex with men (MSM) patient at day 120.ConclusionsFollow-up and compliance rates in SA victims were poor. In addition, > 50% of the patients experienced AEs, which were the main reason for PEP interruption. Strategies to increase follow-up testing and new better tolerated drug regimens must be investigated to address these issues.

Project description:Background: Mitochondrial genome has been used across multiple fields in research, diagnosis, and toxicogenomics. Several compounds damage mitochondrial DNA (mtDNA), including biological and therapeutic agents like the human immunodeficiency virus (HIV) but also its antiretroviral treatment, leading to adverse clinical manifestations. HIV-infected and treated patients may show impaired mitochondrial and metabolic profile, but specific contribution of viral or treatment toxicity remains elusive. The evaluation of HIV consequences without treatment interference has been performed in naïve (non-treated) patients, but assessment of treatment toxicity without viral interference is usually restricted to in vitro assays. Objective: The objective of the present study is to determine whether antiretroviral treatment without HIV interference can lead to mtDNA disturbances. We studied clinical, mitochondrial, and metabolic toxicity in non-infected healthy patients who received HIV post-exposure prophylaxis (PEP) to prevent further infection. We assessed two different PEP regimens according to their composition to ascertain if they were the cause of tolerability issues and derived toxicity. Methods: We analyzed reasons for PEP discontinuation and main secondary effects of treatment withdrawal, mtDNA content from peripheral blood mononuclear cells and metabolic profile, before and after 28 days of PEP, in 23 patients classified depending on PEP composition: one protease inhibitor (PI) plus Zidovudine/Lamivudine (PI plus AZT + 3TC; n = 9) or PI plus Tenofovir/Emtricitabine (PI plus TDF + FTC; n = 14). Results: Zidovudine-containing-regimens showed an increased risk for drug discontinuation (RR = 9.33; 95% CI = 1.34-65.23) due to adverse effects of medication related to gastrointestinal complications. In the absence of metabolic disturbances, 4-week PEP containing PI plus AZT + 3TC led to higher mitochondrial toxicity (-17.9 ± 25.8 decrease in mtDNA/nDNA levels) than PI plus TDF + FTC (which increased by 43.2 ± 24.3 units mtDNA/nDNA; p < 0.05 between groups). MtDNA changes showed a significant and negative correlation with baseline alanine transaminase levels (p < 0.05), suggesting that a proper hepatic function may protect from antiretroviral toxicity. Conclusions: In absence of HIV infection, preventive short antiretroviral treatment can cause secondary effects responsible for treatment discontinuation and subclinical mitochondrial damage, especially pyrimidine analogs such as AZT, which still rank as the alternative option and first choice in certain cohorts for PEP. Forthcoming efforts should be focused on launching new strategies with safer clinical and mitotoxic profile.

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Countering the rise of syphilis: A role for doxycycline post-exposure prophylaxis?

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