A neural circuit for male sexual behavior and reward.

Male sexual behavior is innate and rewarding. Despite its centrality to reproduction, a molecularly specified neural circuit governing innate male sexual behavior and reward remains to be characterized. We have discovered a developmentally wired neural circuit necessary and sufficient for male mating. This circuit connects chemosensory input to BNSTprTac1 neurons, which innervate POATacr1 neurons that project to centers regulating motor output and reward. Epistasis studies demonstrate that BNSTprTac1 neurons are upstream of POATacr1 neurons, and BNSTprTac1-released substance P following mate recognition potentiates activation of POATacr1 neurons through Tacr1 to initiate mating. Experimental activation of POATacr1 neurons triggers mating, even in sexually satiated males, and it is rewarding, eliciting dopamine release and self-stimulation of these cells. Together, we have uncovered a neural circuit that governs the key aspects of innate male sexual behavior: motor displays, drive, and reward.

Periodic Remodeling in a Neural Circuit Governs Timing of Female Sexual Behavior.

Behaviors are inextricably linked to internal state. We have identified a neural mechanism that links female sexual behavior with the estrus, the ovulatory phase of the estrous cycle. We find that progesterone-receptor (PR)-expressing neurons in the ventromedial hypothalamus (VMH) are active and required during this behavior. Activating these neurons, however, does not elicit sexual behavior in non-estrus females. We show that projections of PR+ VMH neurons to the anteroventral periventricular (AVPV) nucleus change across the 5-day mouse estrous cycle, with ∼3-fold more termini and functional connections during estrus. This cyclic increase in connectivity is found in adult females, but not males, and regulated by estrogen signaling in PR+ VMH neurons. We further show that these connections are essential for sexual behavior in receptive females. Thus, estrogen-regulated structural plasticity of behaviorally salient connections in the adult female brain links sexual behavior to the estrus phase of the estrous cycle.

Limbic Neurons Shape Sex Recognition and Social Behavior in Sexually Naive Males.

Sexually naive animals have to distinguish between the sexes because they show species-typical interactions with males and females without meaningful prior experience. However, central neural pathways in naive mammals that recognize sex of other individuals remain poorly characterized. We examined the role of the principal component of the bed nucleus of stria terminalis (BNSTpr), a limbic center, in social interactions in mice. We find that activity of aromatase-expressing BNSTpr (AB) neurons appears to encode sex of other animals and subsequent displays of mating in sexually naive males. Silencing these neurons in males eliminates preference for female pheromones and abrogates mating success, whereas activating them even transiently promotes male-male mating. Surprisingly, female AB neurons do not appear to control sex recognition, mating, or maternal aggression. In summary, AB neurons represent sex of other animals and govern ensuing social behaviors in sexually naive males.

Biochemical evidence accumulates across neurons to drive a network-level eruption.

Neural network computations are usually assumed to emerge from patterns of fast electrical activity. Challenging this view, we show that a male fly's decision to persist in mating hinges on a biochemical computation that enables processing over minutes to hours. Each neuron in a recurrent network contains slightly different internal molecular estimates of mating progress. Protein kinase A (PKA) activity contrasts this internal measurement with input from the other neurons to represent accumulated evidence that the goal of the network has been achieved. When consensus is reached, PKA pushes the network toward a large-scale and synchronized burst of calcium influx that we call an eruption. Eruptions transform continuous deliberation within the network into an all-or-nothing output, after which the male will no longer sacrifice his life to continue mating. Here, biochemical activity, invisible to most large-scale recording techniques, is the key computational currency directing behavior and motivational state.

Sexual Incentive Motivation and Sexual Behavior: The Role of Consent.

The generalized social concern with sexual harassment and nonconsensual sex makes it imperative to incorporate notions of consent in any analysis of human sexual interactions. Such interactions follow an ordered sequence of events, starting with the perception of a sexual incentive, followed by an approach to it, genital interaction, and eventually orgasm. Consent from the partner is needed at every stage. At some points in this chain of events, the individuals involved make cognitive evaluations of the context and predictions of the likelihood for obtaining consent for proceeding to the next phase. Processes such as communication of consent or lack thereof, sexual decision making, and interpretation of cues emitted by the partner are decisive. Increased sexual motivation may influence these processes. However, available data make it possible to ascertain that enhanced motivation has no, or at most minor, effects, thereby invalidating the old assumption that heightened sexual motivation leads to impaired control.

Female sexual behavior is disrupted in a preclinical mouse model of PCOS via an attenuated hypothalamic nitric oxide pathway.

Women with polycystic ovary syndrome (PCOS) frequently experience decreased sexual arousal, desire, and sexual satisfaction. While the hypothalamus is known to regulate sexual behavior, the specific neuronal pathways affected in patients with PCOS are not known. To dissect the underlying neural circuitry, we capitalized on a robust preclinical animal model that reliably recapitulates all cardinal PCOS features. We discovered that female mice prenatally treated with anti-Müllerian hormone (PAMH) display impaired sexual behavior and sexual partner preference over the reproductive age. Blunted female sexual behavior was associated with increased sexual rejection and independent of sex steroid hormone status. Structurally, sexual dysfunction was associated with a substantial loss of neuronal nitric oxide synthase (nNOS)-expressing neurons in the ventromedial nucleus of the hypothalamus (VMH) and other areas of hypothalamic nuclei involved in social behaviors. Using in vivo chemogenetic manipulation, we show that nNOSVMH neurons are required for the display of normal sexual behavior in female mice and that pharmacological replenishment of nitric oxide restores normal sexual performance in PAMH mice. Our data provide a framework to investigate facets of hypothalamic nNOS neuron biology with implications for sexual disturbances in PCOS.

The doublesex gene regulates dimorphic sexual and aggressive behaviors in Drosophila.

Most animal species display dimorphic sexual behaviors and male-biased aggressiveness. Current models have focused on the male-specific product from the fruitless (fruM) gene, which controls male courtship and male-specific aggression patterns in fruit flies, and describe a male-specific mechanism underlying sexually dimorphic behaviors. Here we show that the doublesex (dsx) gene, which expresses male-specific DsxM and female-specific DsxF transcription factors, functions in the nervous system to control both male and female sexual and aggressive behaviors. We find that Dsx is not only required in central brain neurons for male and female sexual behaviors, but also functions in approximately eight pairs of male-specific neurons to promote male aggressiveness and approximately two pairs of female-specific neurons to inhibit female aggressiveness. DsxF knockdown females fight more frequently, even with males. Our findings reveal crucial roles of dsx, which is broadly conserved from worms to humans, in a small number of neurons in both sexes to establish dimorphic sexual and aggressive behaviors.

Ancestral sex-role plasticity facilitates the evolution of same-sex sexual behavior.

Recent attempts to explain the evolutionary prevalence of same-sex sexual behavior (SSB) have focused on the role of indiscriminate mating. However, in many cases, SSB may be more complex than simple mistaken identity, instead involving mutual interactions and successful pairing between partners who can detect each other's sex. Behavioral plasticity is essential for the expression of SSB in such circumstances. To test behavioral plasticity's role in the evolution of SSB, we used termites to study how females and males modify their behavior in same-sex versus heterosexual pairs. Male termites follow females in paired "tandems" before mating, and movement patterns are sexually dimorphic. Previous studies observed that adaptive same-sex tandems also occur in both sexes. Here we found that stable same-sex tandems are achieved by behavioral plasticity when one partner adopts the other sex's movements, resulting in behavioral dimorphism. Simulations based on empirically obtained parameters indicated that this socially cued plasticity contributes to pair maintenance, because dimorphic movements improve reunion success upon accidental separation. A systematic literature survey and phylogenetic comparative analysis suggest that the ancestors of modern termites lack consistent sex roles during pairing, indicating that plasticity is inherited from the ancestor. Socioenvironmental induction of ancestral behavioral potential may be of widespread importance to the expression of SSB. Our findings challenge recent arguments for a prominent role of indiscriminate mating behavior in the evolutionary origin and maintenance of SSB across diverse taxa.

Two-Step Actions of Testicular Androgens in the Organization of a Male-Specific Neural Pathway from the Medial Preoptic Area to the Ventral Tegmental Area for Modulating Sexually Motivated Behavior.

The medial preoptic area (MPOA) is a sexually dimorphic region of the brain that regulates social behaviors. The sexually dimorphic nucleus (SDN) of the MPOA has been studied to understand sexual dimorphism, although the anatomy and physiology of the SDN is not fully understood. Here, we characterized SDN neurons that contribute to sexual dimorphism and investigated the mechanisms underlying the emergence of such neurons and their roles in social behaviors. A target-specific neuroanatomical study using transgenic mice expressing Cre recombinase under the control of Calb1, a gene expressed abundantly in the SDN, revealed that SDN neurons are divided into two subpopulations, GABA neurons projecting to the ventral tegmental area (VTA), where they link to the dopamine system (CalbVTA neurons), and GABA neurons that extend axons in the MPOA or project to neighboring regions (CalbnonVTA neurons). CalbVTA neurons were abundant in males, but were scarce or absent in females. There was no difference in the number of CalbnonVTA neurons between sexes. Additionally, we found that emergence of CalbVTA neurons requires two testicular androgen actions that occur first in the postnatal period and second in the peripubertal period. Chemogenetic analyses of CalbVTA neurons indicated a role in modulating sexual motivation in males. Knockdown of Calb1 in the MPOA reduced the intromission required for males to complete copulation. These findings provide strong evidence that a male-specific neural pathway from the MPOA to the VTA is organized by the two-step actions of testicular androgens for the modulation of sexually motivated behavior.SIGNIFICANCE STATEMENT The MPOA is a sexually dimorphic region of the brain that regulates social behaviors, although its sexual dimorphism is not fully understood. Here, we describe a population of MPOA neurons that contribute to the sexual dimorphism. These neurons only exist in masculinized brains, and they project their axons to the ventral tegmental area, where they link to the dopamine system. Emergence of such neurons requires two testicular androgen actions that occur first in the postnatal period and second in the peripubertal period. These MPOA neurons endow masculinized brains with a neural pathway from the MPOA to the ventral tegmental area and modulate sexually motivated behavior in males.

2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease." METHODS: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Neuropilin-1 expression in GnRH neurons regulates prepubertal weight gain and sexual attraction.

Hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH), the "master molecule" regulating reproduction and fertility, migrate from their birthplace in the nose to their destination using a system of guidance cues, which include the semaphorins and their receptors, the neuropilins and plexins, among others. Here, we show that selectively deleting neuropilin-1 in new GnRH neurons enhances their survival and migration, resulting in excess neurons in the hypothalamus and in their unusual accumulation in the accessory olfactory bulb, as well as an acceleration of mature patterns of activity. In female mice, these alterations result in early prepubertal weight gain, premature attraction to male odors, and precocious puberty. Our findings suggest that rather than being influenced by peripheral energy state, GnRH neurons themselves, through neuropilin-semaphorin signaling, might engineer the timing of puberty by regulating peripheral adiposity and behavioral switches, thus acting as a bridge between the reproductive and metabolic axes.

Modelling the impact of vaccination and sexual behaviour adaptations on mpox cases in the USA during the 2022 outbreak.

BACKGROUND: The 2022 mpox outbreak has infected over 30 000 people in the USA, with cases declining since mid-August. Infections were commonly associated with sexual contact between men. Interventions to mitigate the outbreak included vaccination and a reduction in sexual partnerships. Understanding the contributions of these interventions to decreasing cases can inform future public health efforts. METHODS: We fit a dynamic network transmission model to mpox cases reported by Washington DC through 10 January 2023. This model incorporated both vaccine administration data and reported reductions in sexual partner acquisition by gay, bisexual or other men who have sex with men (MSM). The model output consisted of daily cases over time with or without vaccination and/or behavioural adaptation. RESULTS: We found that initial declines in cases were likely caused by behavioural adaptations. One year into the outbreak, vaccination and behavioural adaptation together prevented an estimated 84% (IQR 67% to 91%) of cases. Vaccination alone averted 79% (IQR 64% to 88%) of cases and behavioural adaptation alone averted 25% (IQR 10% to 42%) of cases. We further found that in the absence of vaccination, behavioural adaptation would have reduced the number of cases, but would have prolonged the outbreak. CONCLUSIONS: We found that initial declines in cases were likely caused by behavioural adaptation, but vaccination averted more cases overall and was key to hastening outbreak conclusion. Overall, this indicates that outreach to encourage individuals to protect themselves from infection was vital in the early stages of the mpox outbreak, but that combination with a robust vaccination programme hastened outbreak conclusion.

Estimated prevalence and associations of sexually transmissible bacterial enteric pathogens in asymptomatic men who have sex with men: a systematic review and meta-analysis.

OBJECTIVE: The reservoir of sexually transmissible bacterial enteric pathogens in asymptomatic men who have sex with men (MSM) may impact future outbreaks, and the evolution of antimicrobial resistance. We aimed to estimate the pooled prevalence and explore any factors associated with Shigella spp, Campylobacter spp, diarrhoeagenic Escherichia coli and Salmonella spp in asymptomatic MSM using the random effects model. METHODS: We searched Embase, MEDLINE, CINAHL and Web of Science Core Collections for manuscripts published up to February 2024. One author screened citations and abstracts; two authors independently conducted a full-text review. We included manuscripts which measured the prevalence of Shigella spp, Campylobacter spp, diarrhoeagenic E. coli and Salmonella spp in asymptomatic MSM. Quality and risk of bias was assessed independently by two authors using the Joanna Briggs Institute critical appraisal tools. We calculated pooled prevalence and CIs using the random effects model. RESULTS: Six manuscripts were included in the final review. The manuscripts were from Australia (n=2), the UK (n=2), the Netherlands (n=1) and the USA (n=1) and included data from 3766 asymptomatic MSM tested for bacterial enteric pathogens. The prevalence of Shigella spp was 1.1% (95% CI 0.7% to 1.7%), Campylobacter spp 1.9% (95% CI 1.5% to 2.5%), diarrhoeagenic E. coli 3.8% (95% CI 2.1% to 6.7%) and Salmonella spp 0.3% (95% CI 0.1% to 0.6%). Two manuscripts demonstrated that the detection of bacterial enteric pathogen was more frequent in asymptomatic MSM using HIV-pre-exposure prophylaxis (PrEP), living with HIV, reporting <5 new sexual partners in the past 3 months, reporting insertive oral-anal sex and group sex compared with MSM testing negative. CONCLUSION: Despite a small number of manuscripts, this review has estimated the pooled prevalence, and highlighted some possible associations with sexually transmissible bacterial enteric pathogens in asymptomatic MSM, which can inform future clinical guidelines, public health control strategies and research to increase our understanding of transmission and the evolution of antimicrobial resistance. PROSPERO REGISTRATION NUMBER: CRD42024518700.

Factors associated with lifetime use of commercial sex work services among Japanese men aged 20-49: findings from a quasi-representative national survey, 2022.

OBJECTIVES: Approximately half of Japanese men aged 20-49 years have purchased sexual services, but data concerning the use of commercial sex work (CSW) in Japan remain scarce. METHODS: We used online survey data from the National Inventory of Japanese Sexual Behavior conducted in 2022 (N=4000 Japanese men aged 20-49 years). We calculated the median number of paid sexual partners over the lifetime. We performed logistic regression analysis to determine the sociodemographic, anthropometric and attitudinal factors associated with any lifetime CSW use among men in Japan. RESULTS: The median number of paid sexual partners reported among men who had ever used CSW was 6 (IQR 3-17) across the lifetime; the corresponding value for those who had ever used CSW in the past year was 2 (IQR 1-4) over the last 12 months. In general, those reporting lifetime use of CSW were significantly more likely than their CSW-naïve counterparts to be older, be married, be heterosexual or bisexual, have higher income and have higher education. Those reporting higher self-rated attractiveness, high or low satisfaction with their sex lives, a desire to increase their frequency of sex and considering sex to be an important aspect of their lives were also found to have a higher likelihood of having used CSW. CONCLUSIONS: High rates of CSW use in Japan likely reflect ease of access, low stigma with respect to use of sexual services and the diversity in the type of services offered. High-income, employed older men have more financial resources at their disposal to purchase services, which can be cost-prohibitive for part-time or unemployed young men with low incomes. These findings will serve as a launchpad for public health efforts directed at promoting safe sexual practices and improved sexually transmitted infection screening rates among users of CSW in Japan.

Early adopters of doxycycline as post-exposure prophylaxis to prevent bacterial sexually transmitted infections in a real-world clinical setting.

OBJECTIVES: Doxycycline as post-exposure prophylaxis (DoxyPEP) is a novel prevention approach which has demonstrated efficacy in preventing bacterial sexually transmitted infections (STIs) in men who have sex with men (MSM) and transgender women (TGW) including people who are living with HIV and those on HIV pre-exposure prophylaxis (PrEP). We evaluated patient knowledge and interest in DoxyPEP, as well as early adopters of its use. METHODS: In 2023, patients presenting for HIV and STI services at a primary care and sexual health clinic were asked about DoxyPEP knowledge, interest and use. Bivariate and multivariate analyses were used to evaluate demographics and behaviours associated with these outcomes. RESULTS: A total of n=421 people presented for care. Of these, 314 were MSM/TGW. Fifteen percent were Black/African-American, and 21% were Hispanic/Latino. A total of 50% of MSM/TGW had heard of DoxyPEP, 49% were interested and 18% reported prior DoxyPEP use. Having a history of STI infection ever (adjusted OR (aOR) 5.95, 95% CI 2.69 to 13.13) and in the past 12 months (aOR 2.99, 95% CI 1.56 to 5.72) were both associated with DoxyPEP use. Individuals who had ever used HIV PrEP had nearly three times the odds of ever taking DoxyPEP (aOR 2.88, 95% CI 1.56 to 5.30). There was no association between the use of DoxyPEP and race, ethnicity or HIV status. CONCLUSIONS: Among MSM and TGW, there is already significant awareness, interest and use of DoxyPEP to prevent bacterial STIs. Public health efforts should focus on improving access and delivery of this STI prevention intervention to MSM and TGW.

Influences affecting decision-making regarding use of pre-exposure prophylaxis among black men who have sex with men in the USA: a systematic review and meta-synthesis.

AIM: To systematically identify, evaluate, and synthesise qualitative research examining positive and negative influences affecting decision-making behaviour among black men who have sex with men (BMSM) in the USA regarding use of pre-exposure prophylaxis (PrEP). BACKGROUND: Used correctly, PrEP is highly efficacious in preventing HIV infection and is available via healthcare services throughout the USA. BMSM are a key target population for HIV prevention services, however their engagement with these services is low. With potential barriers to access ranging from systemic to personal, a phenomenological perspective on the influences affecting individuals' decision-making is essential, helping to better understand the needs of this target population and guide development and delivery of more effective future policy and intervention services. DESIGN: Qualitative meta-synthesis with meta-aggregation. DATA SOURCES: The electronic databases Medline, CINAHL, APA PsycInfo, Embase and Ovid Emcare were comprehensively searched from inception to 21 January 2022. REVIEW METHODS: Systematic identification, quality assessment and synthesis of existing qualitative research according to protocols of meta-aggregation. This included identifying salient study findings and corroborating illustrations from the data, sorting like findings into descriptive themed categories and developing transformative synthesised statements from aggregate appraisal of category findings. RESULTS: Seventeen studies met the inclusion criteria and were assessed to be of acceptable quality. Synthesis of study data yielded 30 categories grouped under five themes: Stigma, Discrimination, Mistrust, PrEP positivity and PrEP negativity. Twelve synthesised statements were produced to provide a summary of the results and suggest improvements to the delivery of future PrEP services and interventions. CONCLUSION: A more targeted approach focused on advocacy and ambassadorship outside of clinical settings may be more influential in positive decision-making regarding use of PrEP in BMSM populations than relying on traditional outreach methods via institutions and their representatives where stigma, mistrust and structural inequalities perpetuate.

From pathology to pleasure: Reframing mechanistic studies on same-sex sexual behavior in primates.

Same-sex sexual behaviors (SSB) in primates have historically been studied as sexual perversions, evolutionary paradoxes, and hormone-driven pathologies. Researchers in recent decades have challenged these perspectives, yet some of the original biases still linger. In this paper, we examine how the study of endocrinological mechanisms in SSB has been influenced by the historical framework of pathology. Societal attitudes and cultural conceptions of human sexuality have led researchers to study SSB in primates as the outcome of "abnormal" processes of "feminization" or "masculinization" of sexual behavior. Here, we argue for a renewed attention to other areas of inquiry regarding the relationship between hormones and SSB, such as the role of pleasure. We briefly review how current knowledge on the neuroendocrinology of pleasure in nonhuman primates may relate to the expression of SSB and highlight oxytocin and dopamine as potentially fruitful areas for future research. We argue that future studies on SSB in primates would benefit from 1) acknowledging how the historical study of SSB as a pathology has shaped mechanistic studies and 2) studying SSB with the same holistic approach as is taken with different-sex sexual behavior (DSB).

How new communication behaviors evolve: Androgens as modifiers of neuromotor structure and function in foot-flagging frogs.

How diverse animal communication signals have arisen is a question that has fascinated many. Xenopus frogs have been a model system used for three decades to reveal insights into the neuroendocrine mechanisms and evolution of vocal diversity. Due to the ease of studying central nervous system control of the laryngeal muscles in vitro, Xenopus has helped us understand how variation in vocal communication signals between sexes and between species is produced at the molecular, cellular, and systems levels. Yet, it is becoming easier to make similar advances in non-model organisms. In this paper, we summarize our research on a group of frog species that have evolved a novel hind limb signal known as 'foot flagging.' We have previously shown that foot flagging is androgen dependent and that the evolution of foot flagging in multiple unrelated species is accompanied by the evolution of higher androgen hormone sensitivity in the leg muscles. Here, we present new preliminary data that compare patterns of androgen receptor expression and neuronal cell density in the lumbar spinal cord - the neuromotor system that controls the hind limb - between foot-flagging and non-foot-flagging frog species. We then relate our work to prior findings in Xenopus, highlighting which patterns of hormone sensitivity and neuroanatomical structure are shared between the neuromotor systems underlying Xenopus vocalizations and foot-flagging frogs' limb movement and which appear to be species-specific. Overall, we aim to illustrate the power of drawing inspiration from experiments in model organisms, in which the mechanistic details have been worked out, and then applying these ideas to a non-model species to reveal new details, further complexities, and fresh hypotheses.

Unheard voices: The sexual challenges of families of patients with bipolar disorder: A qualitative content analysis.

OBJECTIVES: The aim of this study was to explore the voices of the family members of Bipolar Disorder (BD) patients about the challenges ahead of them. METHODS: In this qualitative study, 22 participants shared their experiences of sexual challenges of patients with BD through in-depth, face-to-face, semi-structured interviews. Qualitative content analysis was used for data analysis. RESULTS: An overarching theme entitled "Unheard voices" reflected this experience. It comprised four main categories include sexual promiscuity, a change in sexual patterns, sexual support, and sexual indifference. The results revealed that the families of patients with BD have to deal with sexual promiscuity and change in sexual patterns in their family, and the family system attempts to respond to these changes by sexual support mechanisms and sexual indifference. CONCLUSIONS: Given the significant impact of healthy sexual behaviors on the quality of life of both the individual and the family, therapists and family support systems are advised to strengthen and educate families to support their patients' sexual health and needs and protect their sexual existence; they should also address the sexual challenges faced by these families as a diagnostic and therapeutic priority, and early sexual health interventions should be provided to these families.

Effectiveness of Linkage to Care and Prevention Interventions Following HIV Self-Testing: A Global Systematic Review and Meta-analysis.

Over 38.4 million people were living with HIV globally in 2021. The HIV continuum includes HIV testing, diagnosis, linkage to combined antiretroviral therapy (cART), and retention in care. An important innovation in the HIV care continuum is HIV self-testing. There is a paucity of evidence regarding the effectiveness of interventions aimed at linking self-testers to care and prevention, including pre-exposure prophylaxis (PrEP). To bridge this gap, we carried out a global systematic review and meta-analysis to ascertain the effectiveness of interventions post-HIV self-testing regarding: (1) linkage to care or ART, (2) linkage to PrEP, and (3) the impact of HIV self-test (HIVST) interventions on sexual behaviors. We searched PubMed, Web of Science, SCOPUS, Cochrane Library, CINAHL Plus (EBSCO), MEDLINE (Ovid), Google Scholar, and ResearchGate. We included only published randomized controlled trials (RCTs) and quasi-experiment that compared HIVST to the standard of care (SoC). Studies with sufficient data were aggregated using meta-analysis on RevMan 5.4 at a 95% confidence interval. Cochrane's Q test was used to assess heterogeneity between the studies, while Higgins and Thompson's I2 was used to quantify heterogeneity. Subgroup analyses were conducted to identify the source of heterogeneity. Of the 2669 articles obtained from the databases, only 15 studies were eligible for this review, and eight were included in the final meta-analysis. Overall, linkage to care was similar between the HIVST arm and SoC (effect size: 0.92 [0.45-1.86]; I2: 51%; p: 0.04). In the population subgroup analysis, female sex workers (FSWs) in the HIVST arm were significantly linked to care compared to the SoC arm (effect size: 0.53 [0.30-0.94]; I2: 0%; p: 0.41). HIVST interventions did not significantly improve ART initiation in the HIVST arm compared to the SoC arm (effect size: 0.90 [0.45-1.79]; I2: 74%; p: < 0.001). We found that more male partners of women living with HIV in the SoC arm initiated PrEP compared to partners in the HIVST arm. The meta-analysis showed no difference between the HIVST and SoC arm regarding the number of clients (effect size: - 0.66 [1.35-0.02]; I2: 64%; p: 0.09) and non-clients FSWs see per night (effect size: - 1.45 [- 1.45 to 1.38]; I2: 93%; p: < 0.001). HIVST did not reduce the use of condoms during insertive or receptive condomless anal intercourse among MSM. HIVST does not improve linkage to care in the general population but does among FSWs. HIVST intervention does not improve linkage to ART nor significantly stimulate healthy sexual behaviors among priority groups. The only RCT that linked HIVST to PrEP found that PrEP uptake was higher among partners of women living with HIV in the SoC arm than in the HIVST arm. More RCTs among priority groups are needed, and the influence of HIVST on PrEP uptake should be further investigated.