Young Black women in the southern US face a high HIV burden. While daily oral HIV pre-exposure prophylaxis (PrEP) can effectively prevent HIV, its use is low among Black women. The acceptability of and perceived intention to use emerging PrEP products among young Black women in the southern US are not well understood. Non-oral PrEP alternatives could address challenges to PrEP uptake and reduce health disparities. We conducted virtual semi-structured interviews with Black women aged 18-34 in Atlanta, GA; Baton Rouge, LA; and Jackson, MS, to explore their perspectives on three emerging PrEP products: a long-acting injection, a subdermal implant, and a dual-purpose contraception and HIV prevention intravaginal ring. Seventy-five interviews were conducted from January to October 2021 and analyzed using inductive thematic analysis with NVivo software. Most participants were open to using medication to prevent HIV. The intravaginal ring was the most preferred, primarily due to its dual-purpose function, although it was also frequently rejected. The long-acting injection was the second most preferred and least rejected, perceived as the least invasive. The skin implant was the least preferred and most rejected, viewed as the most invasive. Our findings highlight the need for multiple PrEP options to meet individual preferences. Detailed descriptions, instructions, and experiential learning methods are crucial for choosing non-oral PrEP modalities. Practitioners should address questions and offer peer-based learning opportunities. Designing and promoting PrEP strategies for young Black women should involve close consultation with these consumers.

Screening for depression may identify persons for HIV prevention services and to ensure linkage to care for ART and mental health. We assessed factors associated with depressive symptoms using multiple logistic regression among 15- to 29-year-old gay, bisexual or other men who have sex with men (MSM) and transgender women who have sex with men (TGW) attending HIV prevention clinics at Silom Community Clinic or Bangrak Hospital in Bangkok or Rainbow Clinic in Nakhon Sawan, Thailand. We defined depressive symptoms as a self-report of feelings of sadness that impacted daily life in the past one month. Among 192 MSM, 51 TGW, and 11 gender-questioning persons screened: 12.6% met the criteria for depression; 5.9% had new HIV diagnosis. Independently associated factors which increase the risk of depressive symptoms included: studying in a private school (AOR 7.17); experiencing any type of bullying (AOR 2.8); having a partner with HIV (AOR 4.1); and learning about the study from sources other than a friend (AOR 4.2). Given many youths had depressive symptoms, screening for depression and connection to mental health services would be beneficial in sexual health settings to meet the needs of HIV-vulnerable youth.

INTRODUCTION: Globally, many young women face the overlapping burden of HIV infection and unintended pregnancy. Protection against both may benefit from safe and effective multipurpose prevention technologies. METHODS: Healthy women ages 18-34 years, not pregnant, seronegative for HIV and hepatitis B surface antigen, not using hormonal contraception, and at low risk for HIV were randomized 2:2:1 to continuous use of a tenofovir/levonorgestrel (TFV/LNG), TFV, or placebo intravaginal ring (IVR). In addition to assessing genital and systemic safety, we determined TFV concentrations in plasma and cervicovaginal fluid (CVF) and LNG levels in serum using tandem liquid chromatography-mass spectrometry. We further evaluated TFV pharmacodynamics (PD) through ex vivo CVF activity against both human immunodeficiency virus (HIV)-1 and herpes simplex virus (HSV)-2, and LNG PD using cervical mucus quality markers and serum progesterone for ovulation inhibition. RESULTS: Among 312 women screened, 27 were randomized to use one of the following IVRs: TFV/LNG (n = 11); TFV-only (n = 11); or placebo (n = 5). Most screening failures were due to vaginal infections. The median days of IVR use was 68 [interquartile range (IQR), 36-90]. Adverse events (AEs) were distributed similarly among the three arms. There were two non-product related AEs graded >2. No visible genital lesions were observed. Steady state geometric mean amount (ssGMA) of vaginal TFV was comparable in the TFV/LNG and TFV IVR groups, 43,988 ng/swab (95% CI, 31,232, 61,954) and 30337 ng/swab (95% CI, 18,152, 50,702), respectively. Plasma TFV steady state geometric mean concentration (ssGMC) was <10 ng/ml for both TFV IVRs. In vitro, CVF anti-HIV-1 activity showed increased HIV inhibition over baseline following TFV-eluting IVR use, from a median of 7.1% to 84.4% in TFV/LNG, 15.0% to 89.5% in TFV-only, and -27.1% to -20.1% in placebo participants. Similarly, anti-HSV-2 activity in CVF increased >50 fold after use of TFV-containing IVRs. LNG serum ssGMC was 241 pg/ml (95% CI 185, 314) with rapid rise after TFV/LNG IVR insertion and decline 24-hours post-removal (586 pg/ml [95% CI 473, 726] and 87 pg/ml [95% CI 64, 119], respectively). CONCLUSION: TFV/LNG and TFV-only IVRs were safe and well tolerated among Kenyan women. Pharmacokinetics and markers of protection against HIV-1, HSV-2, and unintended pregnancy suggest the potential for clinical efficacy of the multipurpose TFV/LNG IVR. CLINICAL TRIAL REGISTRATION: NCT03762382 [https://clinicaltrials.gov/ct2/show/NCT03762382].

As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.(§) Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox(¶) during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy(††) in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.(§§) Engaging all persons with HIV in sustained care remains a critical public health priority.

Multipurpose prevention technology intravaginal rings (MPT IVRs) may offer a promising solution for addressing multiple women's sexual and reproductive health needs. We describe MPT IVR acceptability perspectives and examine user experiences of 25 cisgender women aged 18-3years enrolled in a phase IIa randomized, partially blinded, placebo-controlled evaluation of tenofovir-based IVRs with and without contraceptive co-formulation. All took part in an individual, audio-recorded, semi-structured qualitative interview. A thematic analysis of transcribed interviews was completed in MaxQDA. Participants shared little or no knowledge of or experience with IVRs prior to joining the study. Four MPT IVR themes were identified: physical wellbeing, method reliability, personal management, and societal endorsement. Commonly cited of concern, but less described as being experienced, were physical discomforts (e.g., painful insertion/removal; inability to carry out daily activities/chores; foreign body sensation; expulsion; sexual interference, or debilitating side effects). Uncertainty regarding efficacy influenced perspectives about intended prevention benefits. Personal choices in managing reproduction and sexual behaviors had to be congruent with sociocultural values and norms for acceptance beyond the individual user level. Participants viewed broader community acceptance as likely to be mixed given community opposition to the use of modern family planning methods. They also shared concerns that IVR use could lead to infertility, especially among nulliparous women, or that it would encourage premarital sex or high-risk sexual behaviors among adolescent and young women. While a MPT IVR may not be suitable for all women, first-hand testimonials could help influence collective receptivity. Additional community acceptability research is needed. Clinical Trial Registration The study is registered at ClinicalTrials.gov under the identifier NCT03762382.

Monkeypox virus (MPXV) is an orthopoxvirus in the Poxviridae family. The current multinational monkeypox outbreak has now spread to 96 countries that have not historically reported monkeypox, with most cases occurring among gay, bisexual, and other men who have sex with men (1,2). The first monkeypox case in the United States associated with this outbreak was identified in May 2022 in Massachusetts (1); monkeypox has now been reported in all 50 states, the District of Columbia (DC), and one U.S. territory. MPXV is transmitted by close contact with infected persons or animals; infection results in a febrile illness followed by a diffuse vesiculopustular rash and lymphadenopathy. However, illness in the MPXV current Clade II outbreak has differed: the febrile prodrome is frequently absent or mild, and the rash often involves genital, anal, or oral regions (3,4). Although neuroinvasive disease has been previously reported with MPXV infection (5,6), it appears to be rare. This report describes two cases of encephalomyelitis in patients with monkeypox disease that occurred during the current U.S. outbreak. Although neurologic complications of acute MPXV infections are rare, suspected cases should be reported to state, tribal, local, or territorial health departments to improve understanding of the range of clinical manifestations of and treatment options for MPXV infections during the current outbreak.

Currently, no Food and Drug Administration (FDA)-approved treatments for human monkeypox are available. Tecovirimat (Tpoxx), however, is an antiviral drug that has demonstrated efficacy in animal studies and is FDA-approved for treating smallpox. Use of tecovirimat for treatment of monkeypox in the United States is permitted only through an FDA-regulated Expanded Access Investigational New Drug (EA-IND) mechanism. CDC holds a nonresearch EA-IND protocol that facilitates access to and use of tecovirimat for treatment of monkeypox.() The protocol includes patient treatment and adverse event reporting forms to monitor safety and ensure intended clinical use in accordance with FDA EA-IND requirements. The current multinational monkeypox outbreak, first detected in a country where Monkeypox virus infection is not endemic in May 2022, has predominantly affected gay, bisexual, and other men who have sex with men (MSM) (1,2). To describe characteristics of persons treated with tecovirimat for Monkeypox virus infection, demographic and clinical data abstracted from available tecovirimat EA-IND treatment forms were analyzed. As of August 20, 2022, intake and outcome forms were available for 549 and 369 patients, respectively; 97.7% of patients were men, with a median age of 36.5 years. Among patients with available data, 38.8% were reported to be non-Hispanic White (White) persons, 99.8% were prescribed oral tecovirimat, and 93.1% were not hospitalized. Approximately one half of patients with Monkeypox virus infection who received tecovirimat were living with HIV infection. The median interval from initiation of tecovirimat to subjective improvement was 3 days and did not differ by HIV infection status. Adverse events were reported in 3.5% of patients; all but one adverse event were nonserious. These data support the continued access to and treatment with tecovirimat for patients with or at risk for severe disease in the ongoing monkeypox outbreak.

Since May 2022, approximately 20,000 cases of monkeypox have been identified in the United States, part of a global outbreak occurring in approximately 90 countries and currently affecting primarily gay, bisexual, and other men who have sex with men (MSM) (1). Monkeypox virus (MPXV) spreads from person to person through close, prolonged contact; a small number of cases have occurred in populations who are not MSM (e.g., women and children), and testing is recommended for persons who meet the suspected case definition* (1). CDC previously developed five real-time polymerase chain reaction (PCR) assays for detection of orthopoxviruses from lesion specimens (2,3). CDC was granted 510(k) clearance for the nonvariola-orthopoxvirus (NVO)-specific PCR assay by the Food and Drug Administration. This assay was implemented within the Laboratory Response Network (LRN) in the early 2000s and became critical for early detection of MPXV and implementation of public health action in previous travel-associated cases as well as during the current outbreak (4-7). PCR assays (NVO and other Orthopoxvirus laboratory developed tests [LDT]) represent the primary tool for monkeypox diagnosis. These tests are highly sensitive, and cross-contamination from other MPXV specimens being processed, tested, or both alongside negative specimens can occasionally lead to false-positive results. This report describes three patients who had atypical rashes and no epidemiologic link to a monkeypox case or known risk factors; these persons received diagnoses of monkeypox based on late cycle threshold (Ct) values ≥34, which were false-positive test results. The initial diagnoses were followed by administration of antiviral treatment (i.e., tecovirimat) and JYNNEOS vaccine postexposure prophylaxis (PEP) to patients' close contacts. After receiving subsequent testing, none of the three patients was confirmed to have monkeypox. Knowledge gained from these and other cases resulted in changes to CDC guidance. When testing for monkeypox in specimens from patients without an epidemiologic link or risk factors or who do not meet clinical criteria (or where these are unknown), laboratory scientists should reextract and retest specimens with late Ct values (based on this report, Ct ≥34 is recommended) (8). CDC can be consulted for complex cases including those that appear atypical or questionable cases and can perform additional viral species- and clade-specific PCR testing and antiorthopoxvirus serologic testing.

BACKGROUND: Guyana expanded its HIV response in 2005 but the epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections has not been characterized. METHODS: The 2011 Seroprevalence and Behavioral Epidemiology Risk Survey for HIV and STIs collected biologic specimens with demographic and behavioral data from a representative sample of Guyana military personnel. Diagnostics included commercial serum: HIV antibody; total antibody to hepatitis B core (anti-HBc); IgM anti-HBc; hepatitis B surface antigen (HBsAg); anti-HBs; antibody to HCV with confirmatory testing; and HBV DNA sequencing with S gene fragment phylogenetic analysis. Chi-square, p-values and prevalence ratios determined statistical significance. RESULTS: Among 480 participants providing serologic specimens, 176 (36.7%) tested anti-HBc-positive. Overall, 19 (4.0%) participants tested HBsAg-positive; 17 (89.5%) of the HBsAg-positive participants also had detectable anti-HBc, including 1 (5.3%) IgM anti-HBc-positive male. Four (6.8%) females with available HBV testing were HBsAg-positive, all aged 23-29 years. Sixteen (16, 84.2%) HBsAg-positive participants had sufficient specimen for DNA testing. All 16 had detectable HBV DNA, 4 with viral load >2x104IU/ml. Sequencing found: 12 genotype (gt) A1 with 99.9% genetic identity between 1 IgM anti-HBc-positive and 1 anti-HBc-negative; 2 gtD1; and 2 with insufficient specimen. No statistically significant associations between risk factors and HBV infection were identified. CONCLUSIONS: Integrated HIV surveillance identified likely recent adult HBV transmission, current HBV infection among females of reproductive age, moderate HBV infection prevalence (all gtA1 and D1), no HCV infections and low HIV frequency among Guyana military personnel. Integrated HIV surveillance helped characterize HBV and HCV epidemiology, including probable recent transmission, prompting targeted responses to control ongoing HBV transmission and examination of hepatitis B vaccine policies.

BACKGROUND: Dissolvable microneedle patches (dMNPs) provide ease of deployment and eliminate need for hypodermic needle disposal after conventional vaccinations. In this study, immunogenicity of dMNP delivery of adjuvant-free monovalent hepatitis B surface antigen (HBsAg) vaccine (AFV) to standard intramuscular (IM) injection of monovalent aluminum-adjuvanted monovalent hepatitis B vaccine (AAV) were compared in rhesus macaques. METHODS: Sixteen macaques were immunized twice in 4 groups: dMNP delivery of 24 +/- 8microg (n=4) or 48 +/- 14microg (n=4) AFV; IM injection of 10microg AFV (IM AFV, n=4); and IM injection of 10microg AAV (IM AAV, n=4). Levels of hepatitis B surface antibody and HBsAg-specific T-cell responses were analyzed. RESULTS: Six of 8 animals with dMNP delivery of AFV had anti-HBs levels >/=10 mIU/ml after the first vaccine dose. After dMNP delivery of AFV, IFN-gamma, IL-2, and IL-4 production by HBsAg-specific T-cells were detected. A statistically significant positive correlation was detected between anti-HBs levels and HBsAg-specific IFN-gamma and IL-2 (Th1-type cytokine) and IL-4 (Th2-type cytokine) producing cells in all anti-HBs positive animals. CONCLUSIONS: dMNP delivery of AFV can elicit seroprotective anti-HBs levels in rhesus macaques that correlate in human seroprotection, and could be particularly promising for hepatitis B vaccine birth dose delivery in resource-constrained regions.

Background: Hepatitis B affects 257 million people worldwide. Mother-to-child hepatitis B virus (HBV) transmission is a preventable cause of substantial morbidity and mortality and poses greatest risk for developing chronic HBV infection. The World Health Organization recommends that all countries institute universal hepatitis B birth dose (HepB BD) vaccination during the first 24 h of life, followed by timely completion of routine immunization. The objective of this analysis was to assess the cost-effectiveness of adding HepB BD vaccination among sub-Saharan African refugee populations where the host country's national immunization policy includes HepB BD. Methods: We performed a cost-effectiveness analysis of three hepatitis B vaccination strategy scenarios for camp-based refugee populations in the African Region (AFR): routine immunization (RI), RI plus universal HepB BD, and RI plus HepB BD only for newborns of hepatitis B surface antigen-positive mothers identified through rapid diagnostic testing (RDT). We focused analyses on refugee populations living in countries that include HepB BD in national immunization schedules: Djibouti, Algeria and Mauritania. We used a decision tree model to estimate costs of vaccination and testing, and costs of life-years lost due to complications of chronic hepatitis B. Results: Compared with RI alone, addition of HepB BD among displaced Somali refugees in Djibouti camps would save 9807 life-years/year, with an incremental cost-effectiveness ratio (ICER) of 0.15 USD (US dollars) per life-year saved. The RI plus HepB BD strategy among Western Saharan refugees in Algerian camps and Malian refugees in Mauritania camps would save 27,108 life-years/year with an ICER of 0.11 USD and 18,417 life-years/year with an ICER of 0.16 USD, respectively. The RI plus RDT-directed HepB BD was less cost-effective than RI plus delivery of universal HepB BD vaccination or RI alone. Conclusions: Based on our model, addition of HepB BD vaccination is very cost-effective among three sub-Saharan refugee populations, using relative life-years saved. This analysis shows the potential benefit of implementing HepB BD vaccination among other camp-based refugee populations as more AFR countries introduce national HepB BD policies.

Chronic Hepatitis B virus infection remains a major global public health problem, accounting for about 887,000 deaths in 2015. Perinatal and early childhood infections are strongly associated with developing chronic hepatitis B. Adding a birth dose of the hepatitis B vaccine (HepB BD) to routine childhood vaccination can prevent over 85% of these infections. However, HepB BD coverage remains low in many global regions, with shortages of birth attendants trained to vaccinate and limited HepB BD supply at birth. To address the challenges, we developed coated metal microneedle patches (cMNPs) and dissolvable microneedle patches (dMNPs) that deliver adjuvant-free hepatitis B vaccine to the skin in a simple-to-administer manner. The dMNP contains micron-scale, solid needles encapsulating vaccine antigen and dissolve in the skin, generating no sharps waste. We delivered HepB BD via cMNP to BALB/c mice and via dMNP to both mice and rhesus macaques. Both cMNP and dMNP were immunogenic, generating hepatitis B surface antibody levels similar to human seroprotection. Biomechanical analysis showed that at high forces the microneedles failed mechanically by yielding but microneedles partially blunted by axial compression were still able to penetrate skin. Overall, this study indicates that with further development, dMNPs could offer a method of vaccination to increase HepB BD access and reduce needle waste in developing countries.