Group sex and behavior change associated with the 2022 Mpox outbreak among men who have sex with men in Southern California.

BACKGROUND: The Monkeypox (Mpox) outbreak disproportionately affected sexually active gay, bisexual, and other men who have sex with men. To understand community-level changes in sexual behavior, we surveyed individuals in a semi-urban area in Southern California. METHODS: Participants were recruited between October 2022 to April 2023, using palm cards, and geolocation-focused online advertisements on social media and dating apps. Eligible participants were male, ≥18 years, reported sex with men, residents of San Bernardino or Riverside counties, California, Human Immunodeficiency Virus (HIV)-negative, currently not taking pre-exposure prophylaxis (PrEP). Descriptive analyses were performed. Chi-square, Fisher's exact, and Student's T-tests examined the association between group sex behaviors and demographics. RESULTS: We enrolled 91 gay, bisexual, and other men who have sex with men with a median age of 35 years (range 18-70 years). Nearly half reported having participated in group sex in the past year. Overall, 48.9% of group sex participants reported changing their sexual behaviors to prevent Mpox transmission, with limiting the number of sex partners being the most reported prevention strategy (47.6%). To prevent Mpox infection, participants that engage in group sex reported limiting the number of sex partners (34.4%), using condoms for anal sex (16.7%), avoiding crowded social venues (14.3%), and asking partners about Mpox symptoms before sex (9.5%). CONCLUSION: Survey participants reported modest sexual behavior changes in response to the Mpox outbreak. Group sex may increase the risk for Mpox, HIV, and other sexually transmitted infections; therefore, public health messages should include specific discussion of safer group sex practices in sexual health promotion.

Safety of Linezolid During Pregnancy.

ABSTRACT: With growing maternal and congenital syphilis epidemics and shortages of benzathine penicillin, alternative syphilis treatments are needed. Linezolid has shown efficacy against syphilis in animal models. This review found no teratogenic effects. Some adverse effects were seen in animals, but none were reported in a small number of human studies.

Clinical Efficacy of Cefixime for the Treatment of Early Syphilis.

Safe and efficacious alternative treatment options for syphilis are necessary. This randomized, 2-arm, noncomparative pilot study evaluated the efficacy of oral cefixime 400 mg in achieving a ≥4-fold rapid plasma reagin titer decrease by 3 or 6 months after treatment. The proportion of cefixime arm participants treated successfully was 87% (95% confidence interval, 69%-100%; 13/15). Clinical Trials Registration. NCT03752112.

Interest, Concerns, and Attitudes Among Men Who Have Sex With Men and Health Care Providers Toward Prophylactic Use of Doxycycline Against Chlamydia trachomatis Infections and Syphilis.

BACKGROUND: Prophylactic administration of doxycycline is regarded as a potential new public health strategy to combat the rising rates of Chlamydia trachomatis infections and syphilis among men who have sex with men. We conducted a survey-based study to evaluate how community members and health care providers in Southern California would perceive doxycycline preexposure/postexposure prophylaxis (PrEP/PEP) to predict its acceptability and identify potential areas of concern. METHODS: We conducted an online cross-sectional survey among community members who identify as men who have sex with men and health care providers with prescribing authority in Southern California to investigate the current attitudes toward doxycycline PrEP/PEP, including their willingness to accept. We analyzed the data using descriptive statistics and binary logistic regression. RESULTS: Among 212 enrolled community member participants, 67.5% indicated they would take doxycycline PrEP/PEP if offered by their provider. Higher acceptability was significantly associated with several characteristics, including recent history of bacterial sexually transmitted infection diagnosis and current use of HIV PrEP. For health care providers, 89.5% of 76 enrolled participants expressed willingness to prescribe doxycycline PrEP/PEP to their patients if recommended by the Centers for Disease Control and Prevention, but only 43.4% were willing if not. Both community members and health care providers demonstrated high levels of concern toward possible drug resistance. CONCLUSIONS: Doxycycline PrEP/PEP as a preventive strategy against chlamydial infections and syphilis would likely be accepted among community members and health care providers. Clear guidelines from public health officials and further clarification on the strategy's potential impact on developing drug resistance may be necessary to ensure successful implementation.

Doxycycline Prophylaxis for Bacterial Sexually Transmitted Infections.

Bacterial sexually transmitted infections (STIs) have been increasing over the past 2 decades in gay, bisexual, and other men who have sex with men. With the widespread use of early human immunodeficiency virus (HIV) treatment, which virtually eliminates transmission risk, and the availability of HIV pre-exposure prophylaxis, there have been attitudinal changes regarding HIV infection with resultant increases in sexual contact and declines in condom use. Doxycycline is used for primary prophylaxis in a number of infectious diseases. We conducted a state-of-the-art review to examine the current state of research, knowledge gaps, and challenges around the use of doxycycline prophylaxis to prevent syphilis and other STIs. International academic and government experts met in March 2019 to frame the initial inquiry, which was supplemented by focused literature searches. Two small short-term randomized controlled trials examining doxycycline prophylaxis found high efficacy. Five additional clinical studies are underway or in development. Studies differed in design, population, outcomes, and safety measures. Doxycycline prophylaxis for bacterial STIs shows promise. Better and more robust data are needed on efficacy; target population; community acceptability; behavioral risk compensation; doxycycline dose, regimen, and formulation; long-term safety; antimicrobial resistance; cost-effectiveness; and risk-benefit.

Sexually Transmitted Infections in Pregnancy: A Narrative Review of the Global Research Gaps, Challenges, and Opportunities.

BACKGROUND: Sexually transmitted infections (STI), such as chlamydial, gonorrheal, and trichomonal infections, are prevalent in pregnant women in many countries and are widely reported to be associated with increased risk of poor maternal and neonatal outcomes. Syndromic STI management is frequently used in pregnant women in low- and middle-income countries, yet its low specificity and sensitivity lead to both overtreatment and undertreatment. Etiologic screening for chlamydial, gonorrheal, and/or trichomonal infection in all pregnant women combined with targeted treatment might be an effective intervention. However, the evidence base is insufficient to support the development of global recommendations. We aimed to describe key considerations and knowledge gaps regarding chlamydial, gonorrheal, and trichomonal screening during pregnancy to inform future research needed for developing guidelines for low- and middle-income countries. METHODS: We conducted a narrative review based on PubMed and clinical trials registry searches through January 20, 2020, guidelines review, and expert opinion. We summarized our findings using the frameworks adopted by the World Health Organization for guideline development. RESULTS: Adverse maternal-child health outcomes of potential interest are wide-ranging and variably defined. No completed randomized controlled trials on etiologic screening and targeted treatment were identified. Evidence from observational studies was limited, and trials of presumptive STI treatment have shown mixed results. Subgroups that might benefit from specific recommendations were identified. Evidence on harms was limited. Cost-effectiveness was influenced by STI prevalence and availability of testing infrastructure and high-accuracy/low-cost tests. Preliminary data suggested high patient acceptability. DISCUSSION: Preliminary data on harms, acceptability, and feasibility and the availability of emerging test technologies suggest that etiologic STI screening deserves further evaluation as a potential tool to improve maternal and neonatal health outcomes worldwide.

Investigation of syphilis immunology and Treponema pallidum subsp. pallidum biology to improve clinical management and design a broadly protective vaccine: study protocol.

BACKGROUND: The syphilis epidemic continues to cause substantial morbidity and mortality worldwide, particularly in low- and middle-income countries, despite several recent disease control initiatives. Though our understanding of the pathogenesis of this disease and the biology of the syphilis agent, Treponema pallidum subsp. pallidum has improved over the last two decades, further research is necessary to improve clinical diagnosis and disease management protocols. Additionally, such research efforts could contribute to the identification of possible targets for the development of an effective vaccine to stem syphilis spread. METHODS: This study will recruit two cohorts of participants with active syphilis infection, one with de novo infection, one with repeat infection. Whole blood specimens will be collected from each study participant at baseline, 4, 12, 24, 36, and 48 weeks, to track specific markers of their immunological response, as well as to compare humoral reactivity to Treponema pallidum antigens between the two groups. Additionally, we will use serum specimens to look for unique cytokine patterns in participants with early syphilis. Oral and blood samples, as well as samples from any syphilitic lesions present, will also be collected to sequence any Treponema pallidum DNA found. DISCUSSION: By furthering our understanding of syphilis pathogenesis and human host immune response to Treponema pallidum, we will provide important data that will help in development of new point-of-care tests that could better identify active infection, leading to improved syphilis diagnosis and management. Findings could also contribute to vaccine development efforts.

Sociodemographic and clinical characteristics of persons who experienced spontaneous hepatitis C viral clearance.

BACKGROUND: In the United States Hepatitis C virus (HCV) viral clearance is estimated to range between 20 and 30%. The objective of this study was to estimate the frequency of HCV clearance and identify correlates of viral clearance among patients newly identified as HCV antibody positive in a large urban health system in Los Angeles, California. METHODS: We identified patients between November 2015 and September 2017 as part of a newly implemented HCV screening and linkage-to-care program at University of California Los Angeles (UCLA) Health System. All patients were eligible for screening, though there were additional efforts to screen patients born between 1945 and 1965. We reviewed Medical records to categorize anti-HCV antibody positive patients as having spontaneously cleared HCV infection (HCV RNA not detected) or not (HCV RNA detected). We excluded those with a prior history of anti-HCV positivity or history of HCV treatment. We compared differences between those with and without detectable HCV RNA using chi-square test, Fisher's exact test, and t-test as appropriate. We assessed factors associated with HCV clearance using logistic regression analysis. RESULTS: Among the 320 patients included in this study, 56% were male. Baby boomers (52-72 years of age) comprised the single largest age group (62%). We found spontaneous HCV clearance in 58% (n = 185). HCV viral clearance was slightly higher among women as compared to men (63% vs. 53%; p value = 0.07) and varied by race/ethnicity: clearance among Blacks/African Americans was 37% vs. 58% among whites (p value = 0.02). After adjusting for age, race/ethnicity, and sex we found that those diagnosed with chronic kidney disease had a tendency of decreased HCV viral clearance (adjusted OR = 0.34; 95% CI 0.14-1.03). CONCLUSION: Of those patients newly identified as anti-HCV positive, 58% had cleared HCV virus, while the rest showed evidence of active infection. In addition, we found that clearance varied by race/ethnicity and clinical characteristics.

Prevalence and determinants of smoking and secondhand smoke exposure in a rural population of central Greece: a cross-sectional study.

INTRODUCTION: Smoking is one of the most important risk factors for heart and lung disease and is responsible for many forms of cancer. The resulting morbidity and mortality weigh heavily upon countries with high prevalence, such as Greece. According to the Global Adult Tobacco Survey (GATS) Greece, 38.2% of Greeks aged ≥15 years, namely 51.2% of men and 25.7% of women, are smokers. Smoking is also common among the young and people of high education. Despite laws prohibiting smoking at indoor places, exposure to environmental tobacco is very high both in private and public places. The study goal was to estimate the prevalence and characteristics of smoking, the level of tobacco exposure and the factors that affect both in a rural population. METHODS: A cross-sectional household study was conducted using the GATS questionnaire in a rural borough of Thessaly, Greece. Eligible participants were permanent residents of the selected villages, aged ≥18 years and they were selected by a combination of stratified sampling with probability proportional to size, random sampling and convenience sampling. Population demographics, current smoking status and tobacco use patterns, exposure to secondhand smoke, attitudes and knowledge on smoking were recorded. Analyses were performed according to the GATS manuals using the SPSS complex samples module. RESULTS: A total of 330 adults participated in the study (168 men, 162 women). The mean age of the sample was 54.2±17.75 years (range 18.5-86.1 years). Smoking prevalence was 32.4%; 46.4% (95% confidence interval (CI) 37.8-55.3%) of men and 17.9% (95%CI 12.0-25.9%) of women were smokers. Smoking was also common among the young, people with secondary education and high school graduates. The manufactured cigarette was the most preferred tobacco product. Daily smokers consumed on average 20.6 (95%CI 17.67-23.52) cigarettes per day. Men smoked more cigarettes and started at an earlier age than women. Overall exposure to environmental tobacco smoke was high among the population. Men, individuals aged 18-24 years and 40-54 years were more exposed than their counterparts. Places where high exposure was recorded included restaurants (80.0%, 95%CI 76.0-83.5%), bars (87.8%, 95%CI 75.7-94.3%) and coffee shops (82.6%, 95%CI 68.4-91.3%). Six out of ten (62.1%, 95%CI 51.7-71.5%) workers were exposed at their workplace and nearly half were exposed on a daily basis. Prevalence of home exposure was 40.4% (95%CI 32.0-49.5%). The multivariate analysis showed that sex and age were independent predictors of current smoking status, while only sex was independently associated with exposure to secondhand smoke. CONCLUSIONS: There are very few studies studying the characteristics of smoking and tobacco exposure exclusively in rural populations in Greece, such as the present study. Both the high prevalence of smoking and the high levels of exposure to tobacco show a population at increased risk for tobacco-related disease. These call for immediate action to reduce smoking prevalence, help smokers quit and protect the health of non-smokers. The present study's conclusions provide the basis for designing local prevention programs and the baseline for monitoring of future trends in the area.

Proyecto Facil: Using the Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) as a Diagnostic Tool to Improve Access to Human Immunodeficiency Virus Pre-Exposure Prophylaxis (PrEP) via Telemedicine.

Following the underutilization of pre-exposure prophylaxis (PrEP) among Latinx men who have sex with men (MSM) and transgender women in Southern California and the growing use of the delivery of PrEP through telemedicine, the California Department of Public Health implemented a telemedicine component to their already existing assistance program. We used the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to identify and characterize factors inhibiting the successful implementation of the telemedicine program through in-depth, online stakeholder interviews and online community focus groups with Latinx MSM and trans women in southern California. Obstacles reported by stakeholders were complicated enrollment process, preference for in-person care, more appealing private sector models of PrEP, while community members reported low awareness of the program, fear of complications due to immigration status, challenges to fulfill enrollment requirements. Findings can used for the future improvement of the ongoing program, as well as other similar PrEP telemedicine programs.

SARS-CoV-2 viral variants can rapidly be identified for clinical decision making and population surveillance using a high-throughput digital droplet PCR assay.

Epidemiologic surveillance of circulating SARS-CoV-2 variants is essential to assess impact on clinical outcomes and vaccine efficacy. Whole genome sequencing (WGS), the gold-standard to identify variants, requires significant infrastructure and expertise. We developed a digital droplet polymerase chain reaction (ddPCR) assay that can rapidly identify circulating variants of concern/interest (VOC/VOI) using variant-specific mutation combinations in the Spike gene. To validate the assay, 800 saliva samples known to be SARS-CoV-2 positive by RT-PCR were used. During the study (July 2020-March 2022) the assay was easily adaptable to identify not only existing circulating VAC/VOI, but all new variants as they evolved. The assay can discriminate nine variants (Alpha, Beta, Gamma, Delta, Eta, Epsilon, Lambda, Mu, and Omicron) and sub-lineages (Delta 417N, Omicron BA.1, BA.2). Sequence analyses confirmed variant type for 124/124 samples tested. This ddPCR assay is an inexpensive, sensitive, high-throughput assay that can easily be adapted as new variants are identified.

Surveillance of Severe Acute Respiratory Syndrome Coronavirus 2 and Variants Using Digital Droplet Polymerase Chain Reaction at a Large University and Healthcare System in California.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with different infectivity, transmission potential, and morbidity change the characteristics of local epidemics and affect vaccine effectiveness. As part of the University of Southern California COVID-19 Pandemic Research Center's efforts to understand, control, and inform local community on coronavirus disease 2019 (COVID-19), we implemented a SARS-CoV-2 surveillance program among students, employees, and USC Keck Medical Center patients. We present the epidemiology and distribution of SARS-CoV-2 and its variants among the population. Methods: We used digital droplet reverse-transcriptase polymerase chain reaction (PCR) to analyze in real-time remnant SARS-CoV-2 PCR-positive saliva specimens stored at the USC Keck Medicine laboratory between September 2020 and April 2022. Samples were tested for the original strain (A20) and 9 SARS-CoV-2 variants: α(B.1.1.7, Q.1-Q.8), ß(B.1.351, B.1.351.2, B.1.351.3), γ(P.1, P.1.1, P.1.2), δ(B.1.617.2), δ+(or δ417N), ε(B.1.427 and B.1.429), η(B.1.525), λ(C.37) and ο(B.1.1.529, ΒΑ.1, BA.2). We reviewed deidentified health information from positive cases including demographics, history of COVID-19 (eg, symptoms, hospitalizations, and repeat infections), and COVID-19 vaccination status. Results: We reviewed 1169 cases and determined the variant type of 482 specimens: 77 specimens were original strain, 119 "Delta", 165 "Omicron". The original strain was detected during the third and fourth quarters of 2020. The Delta variant appeared during the second quarter of 2021, whereas Omicron appeared in the fourth quarter of 2021. Conclusions: Prospectively tracking SARS-CoV-2 variants in a university population and a hospital system, utilizing a low-cost, high-throughput PCR assay, was feasible. Local variant monitoring remains important to inform prevention and control efforts among university and clinical settings.

Relative Effectiveness of Social Media, Dating Apps, and Information Search Sites in Promoting HIV Self-testing: Observational Cohort Study.

BACKGROUND: Social media sites, dating apps, and information search sites have been used to reach individuals at high risk for HIV infection. However, it is not clear which platform is the most efficient in promoting home HIV self-testing, given that the users of various platforms may have different characteristics that impact their readiness for HIV testing. OBJECTIVE: This study aimed to compare the relative effectiveness of social media sites, dating apps, and information search sites in promoting HIV self-testing among minority men who have sex with men (MSM) at an increased risk of HIV infection. Test kit order rates were used as a proxy to evaluate promotion effectiveness. In addition, we assessed differences in characteristics between participants who ordered and did not order an HIV test kit. METHODS: Culturally appropriate advertisements were placed on popular sites of three different platforms: social media sites (Facebook, Instagram), dating apps (Grindr, Jack'D), and information search sites (Google, Bing). Advertisements targeted young (18-30 years old) and minority (Black or Latinx) MSM at risk of HIV exposure. Recruitment occurred in 2 waves, with each wave running advertisements on 1 platform of each type over the same period. Participants completed a baseline survey assessing sexual or injection use behavior, substance use including alcohol, psychological readiness to test, attitudes toward HIV testing and treatment, and HIV-related stigma. Participants received an electronic code to order a free home-based HIV self-test kit. Follow-up assessments were conducted to assess HIV self-test kit use and uptake of pre-exposure prophylaxis (PrEP) at 14 and 60 days post enrollment. RESULTS: In total, 271 participants were enrolled, and 254 were included in the final analysis. Among these 254 participants, 177 (69.7%) ordered a home HIV self-test kit. Most of the self-test kits were ordered by participants enrolled from dating apps. Due to waves with low enrollment, between wave statistical comparisons were not feasible. Within wave comparison revealed that Jack'D showed higher order rates (3.29 kits/day) compared to Instagram (0.34 kits/day) and Bing (0 kits/day). There were no associations among self-test kit ordering and HIV-related stigma, perceptions about HIV testing and treatment, and mistrust of medical organizations. CONCLUSIONS: Our findings show that using popular dating apps might be an efficient way to promote HIV self-testing. Stigma, perceptions about HIV testing and treatment, or mistrust of medical organizations may not affect order rates of HIV test kits promoted on the internet. TRIAL REGISTRATION: ClinicalTrials.gov NCT04155502; https://clinicaltrials.gov/ct2/show/NCT04155502. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/20417.

Adolescents may accurately self-collect pharyngeal and rectal clinical specimens for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae infection.

BACKGROUND: The COVID-19 pandemic illuminated the benefits of telemedicine. Self-collected specimens are a promising alternative to clinician-collected specimens when in-person testing is not feasible. In this study, we assessed the adequacy of self-collected pharyngeal and rectal specimens for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae among individuals undergoing chlamydia and gonorrhea screening. METHODS: We used data from a large cohort study that included male and female adolescents between the ages of 12-24 years. We considered self-collected specimens adequate for clinical use if the human synthase gene (a control target of the assay) was detected in the specimen. RESULTS: In total, 2,458 specimens were included in the analysis. The human synthase gene was detected in 99.2% (2,439/2,458) of all self-collected specimens, 99.5% (1,108/1,114) of the pharyngeal specimens, and 99.0% (1,331/1,344) of the rectal specimens. CONCLUSION: Self-collected pharyngeal and rectal specimens demonstrated a very high proportion of human gene presence, suggesting that self-collection was accurate. A limitation of this study is that the sample adequacy control detects the presence or absence of the human hydroxymethylbilane synthase gene, but it does not indicate the specific anatomic origin of the human hydroxymethylbilane synthase gene. Self-collected specimens may be an appropriate alternative to clinician-collected specimens.

Mobile health promotion of human immunodeficiency virus self-testing in the United States.

BACKGROUND: Human immunodeficiency virus (HIV) self-testing could overcome barriers associated with traditional HIV testing and increase people's awareness of their serostatus. Mobile health, which utilizes mobile wireless technology, could alleviate concerns associated with HIV self-testing and increase access to this screening test. METHODS: We conducted a PubMed, Google Scholar, and Google search to identify research studies and public health programs in the United States that used mobile health to provide HIV self-testing kits for participants. Nine research studies and two public health programs in the United States met the inclusion criteria and were included in the narrative review. RESULTS: Mobile health interventions delivered through online platforms and smartphone apps tailored towards high-risk populations could promote HIV self-testing distribution, pre- and post-test counseling, and linkage to follow-up care. CONCLUSIONS: Given mobile health's potential to encourage HIV self-testing, prevention, and treatment among high-risk communities, we included recommendations that incorporated this mode of HIV self-testing into public health programs to appropriately address the HIV epidemic in the United States.

Telemedicine: a solution to disparities in human immunodeficiency virus prevention and pre-exposure prophylaxis uptake, and a framework to scalability and equity.

As the group with the highest risk and the lowest pre-exposure prophylaxis (PrEP) utilization, black and Hispanic young men who have sex with men (MSM) face the brunt of the current human immunodeficiency virus (HIV) epidemic within the United States. In this narrative review, we summarized recent interventions that utilize technology (telemedicine) to improve HIV PrEP uptake. We examined the general model of those telemedicine programs and evaluated their success and limitations in addressing PrEP accessibility for at-risk individuals. We also identified the current bottlenecks in the scalability of telemedicine programs, offered suggestions to overcome these barriers, and advocated for a centralized source of funding to increase the accessibility of telemedicine programs for PrEP.

Clinical trial protocol to evaluate the efficacy of cefixime in the treatment of early syphilis.

BACKGROUND: Syphilis rates have been increasing both in the USA and internationally with incidence higher among men-who-have-sex-with-men and people living with human immunodeficiency virus (HIV) infection. Currently, benzathine penicillin is the recommended treatment for syphilis in all patients. Global shortages and cost increases in benzathine penicillin call for alternative treatment options. This study evaluates the efficacy of oral cefixime for the treatment of early syphilis. METHODS: We are conducting a randomized, multisite, open-label, non-comparative clinical trial in Los Angeles and Oakland, CA. Eligible participants are ≥ 18 years old, with primary, secondary, or early latent syphilis (rapid plasma reagin [RPR] titer ≥ 1:8). Patients with HIV infection must have a viral load ≤ 200 copies/mL and CD4+ T cell count ≥ 350 cells/µL during the past 6 months. Participants are randomized to receive either 2.4 M IU benzathine penicillin G intramuscularly once or cefixime 400 mg orally twice a day for 10 days. Participants return at 3, 6, and 12 months post-treatment for follow-up RPR serological testing. The primary outcome is the proportion of participants who achieve ≥ 4-fold RPR titer decrease at 3 or 6 months post-treatment. DISCUSSION: Clinical trials evaluating the efficacy of alternative antibiotics to penicillin are urgently needed. TRIAL REGISTRATION: Clinicaltrials.gov NCT03660488 . Registered on 4 September 2018.

Comparing Web-Based Platforms for Promoting HIV Self-Testing and Pre-Exposure Prophylaxis Uptake in High-Risk Men Who Have Sex With Men: Protocol for a Longitudinal Cohort Study.

BACKGROUND: The majority of those living with HIV in the United States are men who have sex with men (MSM), and young, minority MSM account for more new HIV infections than any other group. HIV transmission can be reduced through detection and early treatment initiation or by starting pre-exposure prophylaxis (PrEP), but rates of testing are lower than recommended among MSM, and PrEP uptake has been slow. Although promoting HIV testing and PrEP uptake by placing advertisements on web-based platforms - such as social media websites and dating apps - is a promising approach for promoting HIV testing and PrEP, the relative effectiveness of HIV prevention advertising on common web-based platforms is underexamined. OBJECTIVE: This study aims to evaluate the relative effectiveness of advertisements placed on 3 types of web-based platforms (social media websites, dating apps, and informational websites) for promoting HIV self-testing and PrEP uptake. METHODS: Advertisements will be placed on social media websites (Facebook, Instagram, and Twitter), dating apps (Grindr, Jack'd, and Hornet), and informational search websites (Google, Yahoo, and Bing) to recruit approximately 400 young (18-30 years old), minority (Black or Latino) MSM at elevated risk of HIV exposure. Recruitment will occur in 3 waves, with each wave running advertisements on 1 website from each type of platform. The number of participants per platform is not prespecified, and recruitment in each wave will occur until approximately 133 HIV self-tests are ordered. Participants will complete a baseline survey assessing risk behavior, substance use, psychological readiness to test, and attitudes and then receive an electronic code to order a free home-based HIV self-test kit. Two follow-ups are planned to assess HIV self-test results and PrEP uptake. RESULTS: Recruitment was completed in July 2020. CONCLUSIONS: Findings may improve our understanding of how the platform users' receptivity to test for HIV differs across web-based platforms and thus may assist in facilitating web-based HIV prevention campaigns. TRIAL REGISTRATION: ClinicalTrials.gov NCT04155502; https://clinicaltrials.gov/ct2/show/NCT04155502. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/20417.