The Use of a Spanish-Translated PrEP Stigma Scale among the Latino Sample of the UNITE Cohort Study.

Pre-Exposure Prophylaxis (PrEP) related stigma is linked to inadequate PrEP uptake, yet there are no validated scales to test this association among Spanish-speaking LSMM. The current study examined if the Spanish-translated PrEP Stigma Scale (PSS) was psychometrically appropriate for implementing in Spanish language dominant Latino/e/x Sexual Minority Men (SMM). Recruitment was conducted using geosocial networking applications, social media sites, and e-mail blasts (N=3,049). First, we utilized Item Response Theory (IRT) modeling to evaluate the reliability of the PSS items and the latent construct across both language groups (nEnglish = 2844 and nSpanish = 205). Subsequently, we applied the PSS scale in a theoretical application by examining its association with key steps in the PrEP uptake cascade (i.e., perceived PrEP candidacy, PrEP willingness, PrEP intentions, and having spoken to provider about PrEP) stratified by language. Results of the IRT analyses provided evidence that the translated version of the PSS was appropriate for use among this sample. Further, among English respondents, PrEP stigma was negatively associated with perceived PrEP candidacy (B=-0.30, p=<.001), PrEP willingness (B=-0.46, p=<.001), and PrEP intentions (B=-0.23, p=.003). PrEP stigma, among Spanish respondents, was not significantly associated with any of the PrEP cascade steps. This study demonstrated that the PSS scale performs adequately for both English and Spanish-speaking Latino SMM. However, researchers and health professionals alike should pay close attention to the nuanced effects in U.S. based English and Spanish language samples as PrEP stigma may impact the PrEP cascade for one language sample and not the other.

Dasatinib interferes with HIV-1 proviral integration and the inflammatory potential of monocyte-derived macrophages from people with HIV.

HIV-1 infection is efficiently controlled by the antiretroviral treatment (ART) but viral persistence in long-lived reservoirs formed by CD4 + T cells and macrophages impedes viral eradication and creates a chronic inflammatory environment. Dasatinib is a tyrosine kinase inhibitor clinically used against chronic myeloid leukemia (CML) that has also showed an anti-inflammatory potential. We previously reported that dasatinib is very efficient at interfering with HIV-1 infection of CD4 + T cells by preserving the antiviral activity of SAMHD1, an innate immune factor that blocks T-cell activation and proliferation and that is inactivated by phosphorylation at T592 (pSAMHD1). We observed that short-term treatment in vitro with dasatinib significantly reduced pSAMHD1 in monocyte-derived macrophages (MDMs) isolated from people with HIV (PWH) and healthy donors, interfering with HIV-1 infection. This inhibition was based on low levels of 2-LTR circles and proviral integration, while viral reverse transcription was not affected. MDMs isolated from people with CML on long-term treatment with dasatinib also showed low levels of pSAMHD1 and were resistant to HIV-1 infection. In addition, dasatinib decreased the inflammatory potential of MDMs by reducing the release of M1-related cytokines like TNFα, IL-1ß, IL-6, CXCL8, and CXCL9, but preserving the antiviral activity through normal levels of IL-12 and IFNγ. Due to the production of M2-related anti-inflammatory cytokines like IL-1RA and IL-10 was also impaired, dasatinib appeared to interfere with MDMs differentiation. The use of dasatinib along with ART could be used against HIV-1 reservoir in CD4 and macrophages and to alleviate the chronic inflammation characteristic of PWH.

Mechanisms and treatments of methamphetamine and HIV-1 co-induced neurotoxicity: a systematic review.

Combination antiretroviral therapy (cART) has dramatically reduced mortality in people with human immunodeficiency virus (HIV), but it does not completely eradicate the virus from the brain. Patients with long-term HIV-1 infection often show neurocognitive impairment, which severely affects the quality of life of those infected. Methamphetamine (METH) users are at a significantly higher risk of contracting HIV-1 through behaviors such as engaging in high-risk sex or sharing needles, which can lead to transmission of the virus. In addition, HIV-1-infected individuals who abuse METH exhibit higher viral loads and more severe cognitive dysfunction, suggesting that METH exacerbates the neurotoxicity associated with HIV-1. Therefore, this review focuses on various mechanisms underlying METH and HIV-1 infection co-induced neurotoxicity and existing interventions targeting the sigma 1 receptor, dopamine transporter protein, and other relevant targets are explored. The findings of this review are envisaged to systematically establish a theoretical framework for METH abuse and HIV-1 infection co-induced neurotoxicity, and to suggest novel clinical treatment targets.

Metagenomic next-generation sequencing targeted and metagenomic next-generation sequencing for pulmonary infection in HIV-infected and non-HIV-infected individuals.

Background: When individuals infected with human immunodeficiency virus (HIV) experience pulmonary infections, they often exhibit severe symptoms and face a grim prognosis. Consequently, early, rapid, and accurate pathogen diagnosis is vital for informing effective treatment strategies. This study aimed to use metagenomic next-generation sequencing (mNGS) and targeted mNGS (tNGS) to elucidate the characteristics of pulmonary infections in HIV and non-HIV individuals. Methods: This study enrolled 90 patients with pulmonary infection at the Department of Infectious Diseases of The First Hospital of Jilin University from June 2022 to May 2023, and they were divided into HIV (n=46) and non-HIV (n=44) infection groups. Their bronchoalveolar lavage fluid (BALF) was collected for mNGS analysis to evaluate the differences in pulmonary infection pathogens, and tNGS detection was performed on BALF samples from 15 HIV-infected patients. Results: A total of 37 pathogens were identified in this study, including 21 bacteria, 5 fungi, 5 viruses, 5 mycobacteria, and 1 mycoplasma. The sensitivity of mNGS was 78.9% (71/90), which is significantly higher than that of conventional methods (CTM) (39/90, P=1.5E-8). The combination of mNGS with CTM can greatly enhance the sensitivity of pathogen detection. The prevalence of Pneumocystis jirovecii (82.6% vs. 9.1%), cytomegalovirus (CMV) (58.7% vs. 0%), and Epstein-Barr virus (EBV) (17.4% vs. 2.3%) was significantly higher in the HIV infection group than in the non-HIV infection group (P<0.05). Although no statistically significant difference was observed, the detection rate of Mycobacteria was higher in HIV-infected patients (17.4%) than in the non-HIV group (6.8%). Furthermore, the tNGS results of BALF from 15 HIV-infected patients were not entirely consistent with the mNGS results., and the concordance rate of tNGS for the detection of main pathogens reached 86.7% (13/15). Conclusion: Next-generation sequencing (NGS) can accurately detect pathogens in the BALF of patients with pulmonary infection. The sensitivity of tNGS is comparable to that of mNGS. Therefore, this technique should be promoted in the clinic for better patient outcomes.

Clinical Diagnostic Challenge in a Case of Disseminated Talaromyces marneffei Infection Misdiagnosed Initially as Pulmonary Tuberculosis: A Case Report and Literature Review.

This case reports a middle-aged male patient who was HIV-negative and initially misdiagnosed as pulmonary tuberculosis but was eventually diagnosed with disseminated Talaromyces marneffei (T. marneffei) infection by next-generation sequencing. The patient presented with respiratory symptoms, recurrent bone pain, and subcutaneous masses as the main symptoms. After one year of antifungal treatment, the symptoms improved obviously, but the symptoms recurred after two weeks of drug withdrawal, and the symptoms were relieved after re-administration of antifungal drugs again. This report highlights the need for the rapid evaluation of fungal infections with metagenomic next-generation sequencing (mNGS) in patients with an inadequate diagnostic basis for tuberculosis infection or a poor response to antituberculosis drugs. In addition, long-term follow-up is needed to observe disease recurrence in patients with disseminated T. marneffei infection.

Developmental Trajectories of Transactional Sex and Age-Disparate Relationships During Adolescence: An HPTN 068 Analysis.

Transactional sex and sexual relationships with older partners increase HIV risk in adolescent girls and young women (AGYW), yet little is known about how these behaviors co-evolve over time. We characterize temporal patterns of transactional sex and age-disparate relationships among AGYW in South Africa. Longitudinal data are from a randomized controlled trial (HPTN 068) of school-aged, HIV-negative, AGYW who attended ≥ 3 study visits. We used group-based trajectory modeling to identify trajectories of transactional sex and age-disparate relationships (partner ≥ 5 years older) in the last year and assessed the interrelationship (conditional probability) between both trajectories. At baseline, median age was 14 years, 14.5% of girls were sexually active, and transactional sex (2.1%) and age-disparate relationships were uncommon (2.7%). We identified two trajectories for transactional sex ("low" [81.9%] and "increasing" [18.1%]) and two for age-disparate relationships ("low" [91.7%] and "increasing" [8.3%]). In a separate joint trajectory analysis, nearly a third (28%) had increasing trajectories for both transactional sex and age-disparate relationships, but most (53%) had a low trajectory of both outcomes. Baseline reporting of early sexual debut, depression, and inequitable gender norms were highest in the increasing transactional sex group. Prior pregnancy, early sexual debut, and IPV were highest among those with increasing age-disparate relationships. AGYW who engage in transactional sex or age-disparate partnerships in early adolescence are more likely to experience sustained engagement in both behaviors as they transition to adulthood, increasing HIV risk. Engaging girls early may maximize effectiveness of behavioral and biomedical HIV prevention efforts.

Travel-associated sexually transmitted infections in Japan: An observational study using imported infectious disease registry data.

International travel is a risk factor for acquiring sexually transmitted infections (STIs) owing to factors such as increased sexual opportunities, a sense of freedom, and the allure of the sex industry. We investigated the incidence of travel-associated STIs in Japan using data from the Japan Registry for Infectious Diseases from Abroad (J-RIDA) reported by 17 participating medical institutions between October 2017 and December 2022. Data were collected on the patients' age, sex, nationality, chief complaint, whether they had visited a travel clinic before travel, travel history, and final diagnosis. Of 4545 cases of travel-associated illness reported, 52 (1.1%) were STIs. Most patients with STIs were male (81%) with a median age of 31 years. HIV (17%), genital herpes (13%), syphilis (13%), and gonorrhea (12%) were the most frequently reported STIs. Only one patient had visited a travel clinic before travel. Promoting awareness and vaccination is crucial for preventing travel-associated STIs.

Using an interactive web application to identify pre-exposure prophylaxis adherence among men who have sex with men.

Background: Men who have sex with men (MSM) are at a high risk for HIV infection. While pre-exposure prophylaxis (PrEP) is an effective oral preventive strategy, its success is largely dependent on consistent medication adherence. Objective: The aim of this study was to develop the machine learning web application and evaluate the performance in predicting PrEP adherence. Methods: The PrEP prospective cohort study of the MSM population conducted in Western China from 2019 to 2023, and we collected adherence data and personal characteristics data from 747 MSM. Predictor variables were screened and the performance of several machine learning methods in predicting nonadherent behaviors were compared. Results: A total of 11 candidate variables were screened that predicted nonadherent behaviors. We developed and evaluated five machine learning models that performed well in predicting adherence. Attitudes of male sexual partners, self-efficacy, HIV testing, number of male sexual partners, and risk perception were the most important predictors of adherence. The optimal prediction model was displayed in a shiny web application for online calculation of the probability of occurrence of nonadherent behaviors among MSM. Conclusions: Machine learning performed well in predicting nonadherent behaviors among MSM. An interactive and intuitive web application can help identify individuals who may have nonadherent behaviors, resulting in improved medication adherence and increased prevention efficacy.

Ultrasound findings of Fitz-Hugh-Curtis Syndrome (FHCS) associated with splenic tuberculosis in an HIV-positive male patient.

Fitz-Hugh-Curtis (FHCS) is characterized by an inflammation of the hepatic capsule concomitant or following pelvic infection due to Chlamydia trachomatis or Neisseria gonorrhea. It is a rare condition occurring most often in a woman of childbearing age and very rare in male patients. Splenic involvement is also a rare form of abdominal tuberculosis. The association of these two conditions is very uncommon. We report the exceptional case of a 58- year-old HIV-positive male patient, with whom abdominal ultrasound helped diagnose FHCS associated with abdominal tuberculosis invovlving the spleen.

Determinants of Late HIV Diagnosis and Advanced HIV Disease Among People Living with HIV in Tanzania.

Background: About half of people infected with Human Immunodeficiency Virus (HIV) often present late for care, resulting in higher healthcare costs, undesired treatment outcomes, and ongoing HIV transmission. This study aimed to assess the prevalence and determinants of late HIV diagnosis and advanced HIV disease (AHD) in Tanzania. Methods: Data were obtained from the 2016-17 Tanzania HIV impact survey. We included 677 newly diagnosed people living with HIV. Late HIV diagnosis and AHD were defined as having a CD4 cell count below 350 cells/µL or 200 cells/µL at diagnosis, respectively. Bivariate and multivariable logistic regression models were fitted to identify the determinants of late HIV diagnosis or AHD. Results: The mean age of the participants was 37.8 years (SD, 12.4). About two-thirds were women (62.6%). The prevalence of late HIV diagnosis was 42.4%, whereas the prevalence of AHD was 17.7%. Factors associated with late HIV diagnosis included age 31-40 years (adjusted odds ratio [aOR] = 1.72, 95% confidence interval [CI]: 1.14-2.60), age ≥41 years (aOR = 1.79, 95% CI: 1.16-2.76), male sex (aOR = 1.88, 95% CI: 1.29-2.73), and active syphilis infection (aOR=2.63, 95% CI: 1.20-5.76). Factors associated with AHD were age 31-40 years (aOR = 2.12, 95% CI: 1.18-3.81), age ≥41 years (aOR = 2.42, 95% CI: 1.32-4.41), male sex (aOR = 1.77, 95% CI: 1.09-2.87), formal education (aOR = 0.49, 95% CI: 0.30-0.81) and active syphilis infection (aOR = 2.49, 95% CI: 1.07-5.77). Conclusion: Late HIV diagnosis and AHD are prevalent among newly diagnosed people living with HIV in Tanzania. Specific subgroups are more likely to present late for HIV care, including middle-aged and older adults, men, illiterate individuals, and those with active syphilis and HIV co-infection. Therefore, we recommend expanding HIV testing services and implementing targeted interventions to improve early access and enrollment in HIV care.

A rare case of progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system (CNS) due to John Cunningham (JC) virus reactivation most often in immunocompromised patients. The brainstem and the anterior corpus callosum are uncommon locations for white matter lesions. We present a case of PML in a 40-year-old female presenting to the emergency department for a tonic seizure with transient postictal confusion. The inpatient workup revealed low cluster of differentiation cell counts (CD3 and CD4), transaminitis, positive drug screen, and abnormal electroencephalogram (EEG). The computed tomogram (CT) of the head and magnetic resonance image (MRI or MR) of the brain showed evidence of subcortical and periventricular white matter lesions in the right hemisphere extending into the brainstem and the left frontal lobe. The hospital course consisted of supportive measures, seizure treatment along with prophylaxis, and human immunodeficiency virus (HIV) management along with prophylactic antibiotics. The patient was discharged with appropriate medications and outpatient referrals. Overall, this case describes some key points. It highlights particular imaging characteristics of PML in the setting of inadequately treated HIV. For example, white matter lesions cross the anterior corpus callosum rather than the splenium, as in the "barbell" sign. In addition, the lesions extend inferiorly along the ipsilateral corticospinal tract into the midbrain and pons. This could be one of the first cases to capture both of these features given the rarity of their concomitant occurrence.

Primary central nervous system lymphoma: A diagnostic challenge in a young immunocompetent patient with limited resources.

Primary central nervous system lymphoma is a rare form of central nervous system malignancy. It predominantly affects immunocompromised individuals and the elderly population. Diffuse large B-cell lymphoma is the most common type. This case report presents a 35-year-old female patient presented with progressive difficulty maintaining balance, headaches, seizures, and blurry vision for 2 months. Physical examination was unremarkable except for sluggish bilateral pupillary reaction and lower extremity weakness. MRI revealed multiple bilateral intraaxial masses. Biopsy and immunohistochemistry confirmed diffuse large B-cell lymphoma, nongerminal center B-cell type. However, the diagnosis was delayed for 4 months. The delay in the diagnosis was caused by its atypical presentation, a surgical site infection, and limited resources, which led the patient to disregard the recommended treatment and leave the hospital against medical advice. Even in the absence of risk factors of primary central nervous system lymphoma, it should be considered as a differential in a young patient with neurologic symptoms and intraaxial mass. Minimally invasive biopsy techniques and readily available immunohistochemistry are essential for prompt diagnosis and guiding treatment.

Interactions between HIV proteins and host restriction factors: implications for potential therapeutic intervention in HIV infection.

Different host proteins target different HIV proteins and antagonize their functions, depending on the stage of the HIV life cycle and the stage of infection. Concurrently, HIV proteins also target and antagonize various different host proteins to facilitate HIV replication within host cells. The preceding quite specific area of knowledge in HIV pathogenesis, however, remains insufficiently understood. We therefore propose, in this review article, to examine and discuss the HIV proteins that counteract those host restriction proteins which results directly in increased infectivity of HIV. We elaborate on HIV proteins that antagonize host cellular proteins to promote HIV replication, and thus HIV infection. We examine the functions and mechanisms via which Nef, Vif, Vpu, Env, Vpr, and Vpx counteract host proteins such as Ser5, PSGL-1, IFITMS, A3G, tetherin, GBP5, SAMHD1, STING, HUSH, REAF, and TET2 to increase HIV infectivity. Nef antagonizes three host proteins, viz., Ser5, PSGL1, and IFITIMs, while Vpx also antagonizes three host restriction factors, viz., SAMHD1, STING, and HUSH complex; therefore, these proteins may be potential candidates for therapeutic intervention in HIV infection. Tetherin is targeted by Vpu and Env, PSGL1 is targeted by Nef and Vpu, while Ser5 is targeted by Nef and Env proteins. Finally, conclusive remarks and future perspectives are also presented.

Preservation of functionality, immunophenotype, and recovery of HIV RNA from PBMCs cryopreserved for more than 20 years.

Background: Many research laboratories have long-term repositories of cryopreserved peripheral blood mononuclear cells (PBMC), which are costly to maintain but are of uncertain utility for immunological studies after decades in storage. This study investigated preservation of cell surface phenotypes and in-vitro functional capacity of PBMC from viraemic HIV+ patients and healthy seronegative control subjects, after more than 20 years of cryopreservation. Methods: PBMC were assessed by 18-colour flow cytometry for major lymphocyte subsets within T, B, NK, and dendritic cells and monocytes. Markers of T-cell differentiation and activation were compared with original immunophenotyping performed in 1995/1996 on fresh blood at the time of collection. Functionality of PBMC was assessed by culture with influenza antigen or polyclonal T-cell activation, to measure upregulation of activation-induced CD25 and CD134 (OX40) on CD4 T cells and cytokine production at day 2, and proliferative CD25+ CD4 blasts at day 7. RNA was extracted from cultures containing proliferating CD4+ blast cells, and intracellular HIV RNA was measured using short amplicons for both the Double R and pol region pi code assays, whereas long 4-kbp amplicons were sequenced. Results: All major lymphocyte and T-cell subpopulations were conserved after long-term cryostorage, except for decreased proportions of activated CD38+HLA-DR+ CD4 and CD8 T cells in PBMC from HIV+ patients. Otherwise, differences in T-cell subpopulations between recent and long-term cryopreserved PBMC primarily reflected donor age-associated or HIV infection-associated effects on phenotypes. Proportions of naïve, memory, and effector subsets of T cells from thawed PBMC correlated with results from the original flow cytometric analysis of respective fresh blood samples. Antigen-specific and polyclonal T-cell responses were readily detected in cryopreserved PBMC from HIV+ patients and healthy control donors. Intracellular HIV RNA quantitation by pi code assay correlated with original plasma viral RNA load results. Full-length intracellular and supernatant-derived amplicons were generated from 5/12 donors, and sequences were ≥80% wild-type, consistent with replication competence. Conclusions: This unique study provides strong rationale and validity for using well-maintained biorepositories to support immunovirological research even decades after collection.

A Rare Modality of Concurrent Cryptococcal and Tubercular Meningitis in a Patient Living With HIV.

Patients with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) and a low CD4 count have decreased humoral and cellular immunity, predisposing them to opportunistic infections. Opportunistic infections are one of the main causes of morbidity and mortality in immunocompromised individuals due to impaired immune systems, particularly in persons living with HIV/AIDS. Common opportunistic infections in patients living with HIV include bacterial infections such as Mycobacterium tuberculosis and Mycobacterium avium complex (MAC); viral infections such as cytomegalovirus (CMV) and herpes simplex virus 1 (HSV-1); fungal infections such as Pneumocystis carinii pneumonia (PCP) and cryptococcal meningitis; and parasitic infections such as cryptosporidiosis and toxoplasmosis. Concurrent infection with cryptococcal and tubercular meningitis in patients with HIV is very rare. Here, we present the case of a 48-year-old male living with HIV who presented with complaints of breathlessness, fever, and weight loss and was evaluated and put on antitubercular medications for pulmonary tuberculosis. However, the presence of a continuous headache led us to investigate further. Upon brain imaging and cerebrospinal fluid evaluation, it was determined to be meningitis due to co-infection with Mycobacterium tuberculosis and Cryptococcus neoformans. The patient was treated with antitubercular therapy along with antifungal therapy. He is under regular follow-up without any further events.

Cervical precancer and invasive cancer among women living with HIV in Latin America: A systematic review and meta-analysis.

BACKGROUND: Data on the occurrence of cervical precancer and cancer among women living with HIV (WLHIV) in Latin American countries (LAC) are scarce and highly heterogeneous. METHODS: We conducted a systematic review summarizing data about the incidence/prevalence of invasive cervical cancer (CC) and high-grade precancerous lesions among WLHIV in LAC. Literature in PubMed and LILACS was searched. The primary outcome was invasive cancer incidence, and prevalence of high-grade lesions as key indicators for the WHO CC elimination strategy. Individual reports on invasive cancer incidence and prevalence of precancerous lesions were obtained, and a random effects meta-analysis was conducted for the latter. RESULTS: In total, 34,343 WLHIV from four studies reporting CC incidence in seven LAC were included, and 6079 WLHIV from 17 studies reporting prevalence of precancerous lesions in three LAC were included. CC incidence ranged between 136.0 and 398.4 per 100,000 WLHIV (with or without antiretroviral therapy). The weighted prevalence of high-grade lesions was 4.1% (95%CI: 3.8%-6.0%) with a double peak at ages 20-24 and 35-39 years. Differences in prevalence of high-grade lesions were also observed by screening approach: co-testing (11.9%), colposcopy (6.0%), cytology (4.2%), and HPV tests (3.2%). CONCLUSIONS: The high incidence of invasive cancer and prevalence of high-grade lesions underline challenges to reach the WHO's elimination goal of CC incidence below four per 100,000 among WLHIV. Moreover, the high prevalence of high-grade lesions at younger ages than in the general population is a call to accelerate the implementation of the new WHO screening recommendations in WLHIV.

Analysis of drug-drug interactions in patients with HIV and metabolic syndrome.

BACKGROUND: People with HIV (PWH) are living longer directly related to highly effective antiretroviral therapy (ART). However, concurrent with improved longevity is the growing prevalence of metabolic comorbidities that drive morbidity and mortality among PWH. There is an increasing repertoire of treatment options for metabolic disorders. Thus, it is important for clinicians to understand the drug-drug interactions (DDIs) between ART and treatments for metabolic disorders. AREAS COVERED: This review will discuss DDIs between contemporary ART and agents used to treat metabolic syndromes (diabetes, dyslipidemia, obesity and hypertension). Literature review of published and unpublished data from manuscripts, conference proceedings, regulatory submissions, and drug prescribing information were conducted from the following sources: PubMed, Google, and Google Scholar through January 2024. EXPERT OPINION: People with HIV have a high prevalence of metabolic disorders. Most significant DDIs between ART and treatments for metabolic disorders are unidirectional with ART as perpetrators, rather than victims, such that careful selection of ART with low DDI propensity can address the concern. However, there are data gaps with DDI data for long-acting ART as well as newer oral injectable medications for diabetes and weight loss. Nanotechnology-based drug delivery platforms hold promise to address some problematic DDIs.

Breadth and polyfunctionality of T cell responses to human cytomegalovirus in men who have sex with men: relationship with HIV infection and frailty.

Cytomegalovirus (CMV)-seropositive adults have large T cell responses to a wide range of CMV proteins; these responses have been associated with chronic inflammation and frailty in people with or without HIV infection. We analyzed the relationships between chronic HIV infection, frailty, and the breadth and polyfunctionality of CD4 and CD8 T cell responses to CMV. Peripheral blood mononuclear cells from 42 men (20 without HIV and 22 with virologically suppressed HIV) in the Multicenter AIDS Cohort Study (MACS) were stimulated with peptide pools spanning 19 CMV open reading frames (ORFs). As measured by flow cytometry and intracellular cytokine staining for IFN-γ, TNF-α, and IL-2, CD8 T cells from men with HIV responded to significantly more CMV ORFs than those from men without HIV. This was primarily due to a broader response to ORFs that are expressed during the late phase of CMV replication. The number of ORFs to which a participant's T cells responded was positively correlated with the sum of all that individual's T cell responses; these correlations were weaker in men with than without HIV. Polyfunctional CMV-specific CD4 responses (production of more than one cytokine) were significantly lower in men with than without HIV. Frailty status did not substantially affect the breadth or magnitude of the CMV-specific T cell responses. These results suggest that immune control of CMV infection is affected more by chronic HIV infection than by frailty. The differences between men with and without HIV were similar to those reported between young and older adults without HIV. IMPORTANCE: T cell responses to chronic cytomegalovirus (CMV) infection have significant biological and clinical implications in HIV infection and aging. Here, we systematically analyzed the breadth, magnitude, and polyfunctionality of T cell responses to multiple CMV antigens in men with and without HIV in the Multicenter AIDS Cohort Study (MACS), a longstanding study of the natural and treated history of HIV-1 infection in men who have sex with men. We found that the breadth and polyfunctionality of T cell responses to CMV were different between men with chronic, treated HIV and those without HIV. The reason for these differences is unknown, but these findings suggest that people with treated HIV may have more frequent CMV reactivation than people without HIV. Differences between people with and without HIV also resembled differences reported between young and older adults without HIV, supporting a role for the immune responses to CMV in the aging process.

Three families of CD4-induced antibodies are associated with the capacity of plasma from people living with HIV to mediate ADCC in the presence of CD4-mimetics.

CD4-mimetics (CD4mcs) are small molecule compounds that mimic the interaction of the CD4 receptor with HIV-1 envelope glycoproteins (Env). Env from primary viruses normally samples a "closed" conformation that occludes epitopes recognized by CD4-induced (CD4i) non-neutralizing antibodies (nnAbs). CD4mcs induce conformational changes on Env resulting in the exposure of these otherwise inaccessible epitopes. Here, we evaluated the capacity of plasma from a cohort of 50 people living with HIV to recognize HIV-1-infected cells and eliminate them by antibody-dependent cellular cytotoxicity (ADCC) in the presence of a potent indoline CD4mc. We observed a marked heterogeneity among plasma samples. By measuring the levels of different families of CD4i Abs, we found that the levels of anti-cluster A, anti-coreceptor binding site, and anti-gp41 cluster I antibodies are responsible for plasma-mediated ADCC in the presence of CD4mc. IMPORTANCE: There are several reasons that make it difficult to target the HIV reservoir. One of them is the capacity of infected cells to prevent the recognition of HIV-1 envelope glycoproteins (Env) by commonly elicited antibodies in people living with HIV. Small CD4-mimetic compounds expose otherwise occluded Env epitopes, thus enabling their recognition by non-neutralizing antibodies (nnAbs). A better understanding of the contribution of these antibodies to eliminate infected cells in the presence of CD4mc could lead to the development of therapeutic cure strategies.

Identifying Effective Strategies for Improving Engagement in HIV Prevention and Care Among Transgender Persons in the United States: A Systematic Review.

This systematic review synthesized published literature (2000 - 2023) to identify HIV interventions specifically designed for transgender persons in the United States (PROSPERO registration number: CRD42021256460). The review also summarized strategies for improving outcomes related to the four pillars of the Ending the HIV Epidemic (EHE) initiative in the United States: Diagnose, Treat, Prevent, and Respond. A comprehensive search was conducted using the Centers for Disease Control and Prevention's HIV Prevention Research Synthesis Project database, which included over 120,000 citations from routine systematic searches in CINAHL, EMBASE, Global Health, MEDLINE, PsycInfo, and Sociological Abstracts. Of 23 interventions that met inclusion criteria, 94% focused on transgender women of color and 22% focused on young transgender persons aged 15-29 years old. Most interventions focused on Treat or Prevent, few focused on Diagnosis, and none focused on Respond. Twenty interventions (87%) showed improvement in at least one EHE related outcome and a quarter of these effective interventions were tested with randomized controlled trials. Common strategies observed in effective interventions include the following: engaging the community in intervention development; pilot-testing with the focus population to ensure appropriateness and acceptability; addressing social determinants of health (e.g. stigma, discrimination, violence) through empowerment and gender-affirming approaches; increasing access to care, prevention, and services through co-location and one-stop shop models; and utilizing peer-led counseling, education, support, and navigation. Continuous effort is needed in addressing gaps, including more research for transgender men and rural settings and for how best to adopt and adapt best practices for subgroups of transgender population.

RESUMEN: Esta revisión sistemática sintetizó la literatura publicada (2000 ­ 2023) para identificar intervenciones relacionadas con el VIH diseñadas específicamente para personas transgénero en los Estados Unidos y resumió las estrategias para mejorar los resultados relacionados con los cuatro pilares de la iniciativa Poner fin a la Epidemia del VIH (EHE por sus siglas en inglés). Diagnosticar, Tratar, Prevenir y Responder. Este protocolo de estudio se registró en PROSPERO (CRD42022364101). Se realizó una búsqueda exhaustiva utilizando la base de datos del Proyecto de Síntesis de Investigación sobre Prevención del VIH de los Centros para el Control y la Prevención de Enfermedades, que incluyó más de 120.000 citas de búsquedas sistemáticas de rutina en CINAHL, EMBASE, Global Health, MEDLINE, PsycInfo y Sociological Abstracts. De las 23 intervenciones que cumplieron con los criterios de inclusión, el 94% se centró en mujeres transgénero de color y el 22% se centró en personas transgénero jóvenes de entre 15 y 29 años. La mayoría de las intervenciones se centraron en los pilares Tratar o Prevenir, pocas se centraron en el pilar de Diagnóstico y ninguna se centró en el pilar de Responder. Veinte intervenciones (87%) mostraron una mejora en al menos un resultado relacionado con la EHE; una cuarta parte de estas intervenciones efectivas se probaron con ensayos controlados aleatorios. Las intervenciones efectivas en todos los pilares compartían características comunes, como la participación de la comunidad en el desarrollo de la intervención; la realización de pruebas piloto con la población objetivo para garantizar la idoneidad y la aceptabilidad; el abordaje de los determinantes sociales de la salud (p.e., el estigma, la discriminación, la violencia, los problemas legales, la vulnerabilidad económica, la vivienda, el transporte, la alimentación) mediante enfoques de empoderamiento y afirmación de género; el aumento del acceso a la atención, la prevención y el servicio (p.e., Mediante la co-ubicación, y el sistema de ventanilla única); y el uso de asesoramiento, educación, apoyo y orientación dirigidos por pares. Se necesita un esfuerzo continuo para abordar las brechas, incluida una mayor investigación para los hombres transgénero y los entornos rurales y para determinar cuál es la mejor manera de adoptar y adaptar las mejores prácticas para los subgrupos de la población transgénero.