The impact of concurrent HIV-infection on women with vulvar cancer: Comparison of clinical characteristics and outcome.

BACKGROUND: HPV-related vulvar cancer is increasing in prevalence, especially in women living with HIV. Treatment of vulva cancer is based on evidence from HPV-independent cancers, which affect older women. The impact of HIV on vulvar cancer characteristics and treatment outcomes needs to be elucidated. PATIENTS AND METHODS: A retrospective observational study compared the clinical characteristics, treatment, and outcomes of 92 HIV-positive and 131 HIV-negative women with vulvar cancer at our institution. Using descriptive statistics, HIV-positive and negative patients were compared and Cox regression models were tested for differences in mortality and recurrence. RESULTS: HIV-positive patients were 20 years younger than HIV-negative patients (p < 0.001). More than 50% of patients presented with advanced stage cancer, however this was independent of HIV-status. Although HIV infection was associated with poorer survival (p = 0.022); rates of cure (p = 0.933) and recurrence rates (p = 0.8) were similar in HIV-positive and negative women. CONCLUSIONS: Vulvar cancer occurs at a much younger age in women living with HIV. Awareness among HIV-positive women and health care providers would lead to diagnosis of vulvar cancer at an earlier stage. Treatment protocols for HPV-related vulvar cancer should not be altered due to HIV status and should take into consideration the young age of the patients.

Retrospective analysis of patients with hepatocellular carcinoma complicated with human immunodeficiency virus infection after hepatectomy.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide, with a 5-year relative survival rate of approximately 18%. The similarity between incidence and mortality (830000 deaths per year) underscores the bleak prognosis associated with the disease. HCC is the fourth most common malignancy and the second leading cause of cancer death in China. Most patients with HCC have a history of chronic liver disease such as chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, alcoholism or alcoholic steatohepatitis, nonalcoholic fatty liver disease, or nonalcoholic steatohepatitis. Early diagnosis and effective treatment are the keys to improving the prognosis of patients with HCC. Although the total number of human immunodeficiency virus (HIV)-infected patients is declining globally the incidence of HCC is increasing in HIV-infected patients, especially those who are coinfected with HBV or HCV. As a result, people infected with HIV still face unique challenges in terms of their risk of developing HCC. AIM: To investigate the survival prognosis and clinical efficacy of surgical resection in patients with HCC complicated with HIV infection. METHODS: The clinical data of 56 patients with HCC complicated with HIV admitted to the Third Affiliated Hospital of Nantong University from January 2013 to December 2023 were retrospectively analyzed. Among these, 27 patients underwent hepatectomy (operation group) and 29 patients received conservative treatment (nonoperation group). All patients signed informed consents in line with the provisions of medical ethics. The general data, clinicopathological features and prognoses for the patients in the two groups were analyzed and the risk factors related to the prognoses of the patients in the operation group were identified. RESULTS: The median disease-free survival (DFS) and overall survival (OS) of HIV-HCC patients in the surgical group were 13 months and 17 months, respectively, and the median OS of patients in the nonsurgical group was 12 months. The OS of the surgical group was significantly longer than that of the control group (17 months vs 12 months, respectively; P < 0.05). The risk factors associated with DFS and OS in the surgical group were initial HIV diagnosis, postoperative microvascular invasion (MVI), a CD4+ T-cell count < 200/µL, Barcelona stage C-D, and men who have sex with men (MSM; P < 0.05). CONCLUSION: Hepatectomy can effectively prolong the survival of patients with HIV-HCC but MVI identified during postoperative pathological examination, late tumor detection, late BCLC stage, CD4+ T < 200/µL and MSM are risk factors affecting the survival and prognosis of patients undergoing hepatectomy. In addition, there were significant differences between the surgical group and the nonsurgical group in terms of the initial diagnosis of HIV, Child-Pugh score, alpha-fetoprotein measurement value, and HART-efficient antiretroviral therapy after the diagnosis of HIV (P < 0.05). Therefore, these factors may also affect the survival and prognosis of patients.

A systematic review and meta-analysis evaluating the effectiveness of minimally supervised home and community exercise interventions in improving physical activity, body adiposity and quality of life in adults living with HIV.

People living with HIV (PLWH) are physically inactive and risk cardiometabolic dysfunction. Home and community exercise (HCE) is pragmatic, cost-effective and improves health in varied chronic conditions. This review aimed to synthesize evidence on the effectiveness of minimally supervised HCE for physical activity (PA), adiposity, quality of life (QoL), and other physical and psychological health indices for PLWH. METHODS: Databases were searched for studies published January 2000 to April 2023. Risk of bias in experimental and quasi-experimental studies was assessed with the Cochrane Risk-of-Bias for Randomized Trials and Risk-of-Bias in Non-Randomized Studies of Interventions tools, respectively. A random-effects meta-analysis was conducted. RESULTS: From 9648 records, 13 studies (14 HCE groups) with 857 PLWH (average ages 29-56 years) were included; 12 comparator and one single group trial. Aerobic and strength HCE significantly improved PA relative to control by 0.377 units (95 %CI = 0.097, 0.657; p = 0.008) and 1097steps/day (95 %CI = 39.27, 2156.62; p = 0.042). There was a reduction from baseline in percent body fat of 3.36 % (95 %CI = -6.10, 0.42; p = 0.025), but no change in BMI (-0.21 kg/m2; 95 %CI = -0.67, 0.24; p = 0.351) relative to control. HCE improved QoL relative to control in the physical domain by 13points (95 %CI = 6.15, 19.86; p < 0.001), but not in other domains like general health (6.6points; 95 %CI = -1.19, 14.36; p < 0.097). HCE completed at moderate intensity or higher was associated with improvement in outcomes more so than lower intensity HCE. Walking-only interventions were at least as beneficial as other activities. No adverse events were recorded. CONCLUSION: Minimally supervised HCE can improve PA, body fat, physical QoL and other health indices in PLWH.

Delving deeper into the mechanisms fundamental to HIV-associated immunopathology using single-cell sequencing techniques: A scoping review of current literature.

Human immunodeficiency virus (HIV) infection has evolved into an established global pandemic over the past four decades; however, despite massive research investment globally, the precise underlying mechanisms which are fundamental to HIV-related pathogenesis remain unclear. Single cell ribonucleic acid (RNA) sequencing methods are increasingly being used for the identification of specific cell-type transcriptional changes in HIV infection. In this scoping review, we have considered information extracted from fourteen published HIV-associated single-cell RNA sequencing-related studies, hoping to throw light on the underlying mechanisms of HIV infection and pathogenesis, and to explore potential candidate biomarkers for HIV disease progression and antiviral treatment. Generally, HIV positive individuals tend to manifest disturbances of frequency of multiple cellular types, and specifically exhibit diminished levels of CD4+ T-cells and enriched numbers of CD8+ T-cells. Cell-specific transcriptional changes tend to be linked to cell permissiveness, hyperacute or acute HIV infection, viremia, and cell productivity. The transcriptomes of CD4+ T-cell and CD8+ T-cell subpopulations are also observed to change in HIV-positive diabetic individuals, spontaneous HIV controllers, individuals with high levels of HIV viremia, and those in an acute phase of HIV infection. The transcriptional changes seen in B cells, natural killer (NK) cells, and myeloid dendritic cells (mDCs) of HIV-infected individuals demonstrate that the humoral immune response, antiviral response, and immune response regulation, respectively, are all altered following HIV infection. Antiretroviral therapy (ART) plays a crucial role in achieving immune reconstitution, in improving immunological disruption, and in mitigating immune system imbalances in HIV-infected individuals, while not fully restoring inherent cellular transcription to levels seen in HIV-negative individuals. The preceding observations not only illustrate compelling advances in the understanding of HIV-associated immunopathogenesis, but also identify specific cell-type transcriptional changes that may serve as potential biomarkers for HIV disease monitoring and therapeutic targeting.

Patients' Preferences for Antiretroviral Therapy Service in Northwest Ethiopia: A Discrete Choice Experiment.

Objective. We aim to evaluate patients' preferences for antiretroviral therapy (ART) to enhance shared decision making in clinical practice in Northwest Ethiopia. Methods. A discrete choice experiment approach was used among adult patients from 36 randomly selected public health facilities from February 6, 2023, to March 29, 2023. A literature review, qualitative work, ranking and rating surveys, and expert consultation were used to identify the attributes. Location, provider, frequency of visit, appointment modality, refill time, and cost of visit were the 6 ART service features chosen. Participants were given the option of choosing between 2 hypothetical differentiated ART delivery models. Mixed logit and latent class analysis were used. Results: Four hundred fifty-six patients completed the choice task. Respondents preferred to receive ART refills alone at health facilities by health care workers without having to have frequent visits and with reduced cost of visit. Overall, the participants valued the cost of the visit the most while they valued the timing of ART refill the least. Participants were willing to pay only for the attributes of frequency of visit and medication refill time. The latent class model with 3 classes provided the best model fit. Location, cost, and frequency were the most important attributes in class 1, class 2, and class 3, respectively. Income and marital status significantly predicted class membership. Conclusions. Respondents preferred to receive refills at health facilities, less frequent visits, individual appointments, service provision by health care workers, and reduced cost of visit. The cost attribute had the greatest impact on the choice of patients. Health care workers should consider the preferences of patients while providing ART services to meet patients' expectations and choices. Highlights: A discrete choice experiment was used to elicit patient preferences.People living with HIV preferred receiving medication refills at health facilities, less frequent visits, individual appointments, service delivery by health care workers, and lower visit costs.Health care workers should consider the preferences of patients while providing ART service to meet their expectations and choices.Scaling up differentiated HIV treatment services is crucial for patient-centered care.

Effectiveness and safety of tildrakizumab in individuals with HIV and psoriasis: A case series.

Psoriasis, a chronic inflammatory skin disease, presents unique challenges when co-occurring with HIV. Tildrakizumab, an IL-23p19 inhibitor, has demonstrated efficacy in treating moderate-to-severe psoriasis. This retrospective case series reports three individuals living with HIV and psoriasis treated with tildrakizumab. Clinical outcomes, including Psoriasis Area and Severity Index (PASI) and HIV viral load, were recorded over a year. All three patients achieved significant clinical improvements with tildrakizumab, with PASI scores improving by over 95%. No adverse effects were reported, and HIV viral loads remained undetectable. Tildrakizumab appears to be a safe and effective treatment option for psoriasis in individuals living with HIV, providing significant benefits without compromising HIV control.

Clinical manifestations and viral kinetics of people with Mpox: A case series during the 2023 outbreak in Taiwan.

Monkeypox (Mpox) has emerged as a global threat since 2022. We reported 14 cases of Mpox in 10 people with HIV (PWH) and 4 people without HIV (PWoH), of whom 64.3% had sexually transmitted co-infections. Severe complications of Mpox and prolonged viral shedding might occur in both PWH and PWoH.

Discovery of new acetamide derivatives of 5-indole-1,3,4-oxadiazol-2-thiol as inhibitors of HIV-1 Tat-mediated viral transcription.

Human immunodeficiency virus-1 (HIV-1) encodes a transcriptional factor called Tat, which is critical for viral transcription. Tat-mediated transcription is highly ordered apart from the cellular manner; therefore, it is considered a target for developing anti-HIV-1 drugs. However, drugs targeting Tat-mediated viral transcription are not yet available. Our high-throughput screen of a compound library employing a dual-reporter assay identified a 1,3,4-oxadiazole scaffold against Tat and HIV-1 infection. Furthermore, a serial structure-activity relation (SAR) study performed with biological assays found 1,3,4-oxadiazole derivatives (9 and 13) containing indole and acetamide that exhibited potent inhibitory effects on HIV-1 infectivity, with half-maximal effective concentrations (EC50) of 0.17 (9) and 0.24 µM (13), respectively. The prominent derivatives specifically interfered with the viral transcriptional step without targeting other infection step(s) and efficiently inhibited the HIV-1 replication cycle in the T cell lines and peripheral blood mononuclear cells infected with HIV-1. Additionally, compared to the wild type, the compounds exhibited similar potency against anti-retroviral drug-resistant HIV-1 strains. In a series of mode-of-action studies, the compounds inhibited the ejection of histone H3 for facilitating viral transcription on the long-terminal repeat (LTR) promoter. Furthermore, SAHA (a histone deacetylase inhibitor) treatment abolished the compound potency, revealing that the compounds can possibly target Tat-regulated epigenetic modulation of LTR to inhibit viral transcription. Overall, our screening identified novel 1,3,4-oxadiazole compounds that inhibited HIV-1 Tat, and subsequent SAR-based optimization led to the derivatives 9 and 13 development that could be a promising scaffold for developing a new class of therapeutic agents for HIV-1 infection.

The Prevalence of HIV Seroconversion in Healthcare Workers Following Sharp Injuries and Exposure to Biofluids.

Background and objective Workplace accidents (WPAs) are a common problem worldwide. They are often considered a public health concern due to the potential transmission of infections such as HIV, hepatitis B, and hepatitis C through sharp devices or direct exposure to biofluids. Post-exposure prophylaxis (PEP) has demonstrated effectiveness in such instances, especially immediately after exposure. The present study aimed to report the prevalence rate of HIV seroconversion following such exposure among healthcare workers (HCWs). Methods We conducted a cross-sectional study involving a database analysis of cases from 2015 to 2024. Central tendency measures were used to describe population characteristics, and rates were calculated using standard methods. Results A total of 514 HCWs were included in the study. The prevalence of WPAs was 13 per 100 HCWs. Regarding WPAs related to HIV exposure, the prevalence was 0.9 per 100 HCWs, with 0% seroconversion thanks to timely PEP. Conclusions WPAs related to HIV exposure are a serious issue for public health systems worldwide. Although protocols are available and no seroconversion cases were reported in the present study, PEP is not always accessible in several settings, increasing the risk of seroconversion. International public policy measures should be uniformly implemented to provide faster access to prophylaxis, educate the personnel, raise awareness about bloodborne diseases, and reduce excessive red tape.

Plasma proteomic profiles of patients with HIV infection and coinfection with hepatitis B/C virus undergoing anti­retroviral therapy.

Chronic liver disease is becoming a leading cause of illness and mortality in patients living with human immunodeficiency virus (HIV; PLWH) undergoing suppressive anti-retroviral therapy. Its primary etiology is coinfection with hepatitis B and C virus (HBV and HCV, respectively). Chronic liver inflammation and fibrosis can potentially lead to the development of hepatocellular carcinoma (HCC). Therefore, monitoring of the disease progression in PLWH is required. The present study aimed to explore plasma protein profiles of PLWH and those coinfected with HBV and HCV using shotgun proteomics. HIV-monoinfected, HIV/HBV-coinfected, HIV/HCV-coinfected and uninfected control individuals were recruited. Patients in the three virus-infected groups had significantly higher levels of liver fibrosis indices (fibrosis-4 score and aspartate aminotransferase to platelet ratio index) compared with the control group. Liquid chromatography-tandem mass spectrometry analysis of plasma samples identified 1,074 proteins that were differentially expressed, where subsequent partial least squares-discriminant analysis model demonstrated clear clustering of proteomes from the four sample groups; 18 proteins that were significantly differentially expressed. Heatmap analysis identified two main groups of proteins, six proteins being upregulated only in the HIV/HBV-coinfection group and 10 proteins downregulated in all three virally infected groups. STITCH 5.0 analysis predicted an interaction network containing two identified proteins in the latter group, specifically ubiquitin interaction motif-containing 1 (UIMC1) and haptoglobin (HP), which are part of the profibrogenic TGF-1ß/SMAD, inflammatory TNF and tumor suppressor BRCA1 pathways. Expression levels of UIMC1 and HP were significantly lower in HIV-infected groups compared with those in uninfected controls. Altogether, these proteomics data provide protein expression profiles potentially associated with HIV infection and coinfection with HBV/HCV, which may be applied to predict progression to advanced liver disease or HCC in PLWH.

A comparative study based on ainuovirine/lamivudine/tenofovir against HIV-1.

BACKGROUND: Ainuovirine, as a third-generation non-nucleoside reverse transcriptase inhibitor against HIV-1, is widely used in China. To evaluate its therapeutic efficacy and disadvantages, a comparative study based on Ainuovirine had been conducted. METHOD: We investigated 199 people living with HIV-1 who received Ainuovirine (ANV)/lamivudine/tenofovir and 202 people living with HIV-1 who received Efavirenz (EFV)/lamivudine/tenofovir. RESULTS: After 48 weeks of therapy, ANV and EFV showed similar viral inhibitory effects. However, in the ANV group, more participants had CD4/CD8 ratios restored to the normal range, lower levels of triglycerides and low-density lipoprotein, relatively normal liver alanine aminotransferase, and fewer adverse events. CONCLUSION: Therefore, due to its role in immune reconstitution, dyslipidemia, and safety, ANV may be a recommended option for people living with HIV-1.

Hepatitis B Virus, Hepatitis C Virus, and Human Immunodeficiency Virus Infection Among Premarital Screening Individuals in Saudi Arabia.

Objective: Premarital screening is one of the most important strategies for preventing infectious diseases such as hepatitis B virus, hepatitis C virus, and human immunodeficiency virus in populations. This study aims to explore the prevalence of these viruses and their association with potential demographic factors among individuals undergoing premarital screening in Saudi Arabia. Methods: A cross-sectional study design using the National Healthy Marriage Program electronic registry in the Saudi Ministry of Health. Patients were selected from the premarital screening tests for the three blood-borne viruses. Data were obtained from January to August 2021 among 114,740 individuals. Results: Hepatitis B virus infection showed the highest prevalence followed by hepatitis C and human immunodeficiency viruses. Among those who were infected, men had higher infectious disease prevalence than women. The central and western regions had the highest percentages of infection. Conclusion: The studied infections pose a continuous public health issue among premarital screening individuals in Saudi Arabia. This study identified important demographic risk factors for these diseases and highlighted the need for future strategies and long-term plans at the national level.

Implementation of routine HIV testing policy in medical admissions in the sultanate of Oman: An experience from the Middle East.

OBJECTIVES: To tackle the issue of late HIV diagnosis in the country, the Ministry of Health (MOH) in Oman introduced a national policy of routine opt-out HIV in medical admission units in September 2022. We hereby report the implementation and outcomes of this policy. METHOD: All patients aged 16-65 years admitted to a medical ward in secondary and local hospitals were offered an HIV test regardless of their symptoms by medical doctors, with training and support from HIV teams. A retrospective review for the period from September 2022 to September 2023 was conducted to determine the HIV testing rate and outcomes of those testing HIV seropositive. RESULT: Over 12 months, there were 23,399 admissions; 6889 had HIV tests. Thirty-two patients (0.46 %) were diagnosed with HIV; all of them were new diagnoses. Two cases were diagnosed during seroconversion. 12 cases had AIDS-defining illnesses. Four contacts were tested HIV positive. Twenty-five out of 28 alive patients are on ART. CONCLUSION: This is the first national policy of a routine opt-out HIV in medical admission units in the MENA region. Our experience showed that, even in low HIV prevalence and high HIV stigma settings, this policy is feasible, acceptable, and effective.

Kikuchi-Fujimoto lymphadenitis in a patient with human immunodeficiency virus infection: The importance of precision pathology.

BACKGROUND: Kikuchi-Fujimoto lymphadenitis (or histiocytic necrotising lymphadenitis) is a rare disease that is usually benign and self-limiting. A higher prevalence is reported amongst East Asian populations. No clear etiology has been identified although it has been associated with some viruses, rarely the Human Immunodeficiency Virus (HIV) and autoimmune pathologies. To date, there has only been a handful of cases reported globally in association with HIV, and this association is even rarer in the Asian context. CASE PRESENTATION: A 20-year-old Asian ethnic Malay male, with no past medical history, presented with daily fevers and chills for 2 weeks associated with constitutional symptoms and bilateral non-tender cervical, axillary and inguinal lymphadenopathy. Full blood count showed lymphocytosis with large granular lymphocytes. HIV viral load returned positive at >10 million copies/mL. His absolute CD4 T helper cell count was 375 cells/uL (7%). The rest of the infective and autoimmune workup were negative. Excision biopsy of an enlarged left cervical lymph node revealed Kikuchi lymphadenitis in the proliferative phase, with no evidence of lymphoproliferative disease. He was started on anti-retroviral therapy with resolution of the lymphadenopathy in 3 months. CONCLUSION: We present a case of Kikuchi lymphadenitis associated with HIV. This highlights that Kikuchi lymphadenitis may mimic sinister pathologies (such as tuberculosis and lymphoma) and that it needs to be considered in the differential diagnosis before empirical treatment for tuberculosis or invasive investigations for lymphoma are done.

Implementation and Evaluation of a Home-Based Pre-Exposure Prophylaxis Monitoring Option: Protocol for a Randomized Controlled Trial.

BACKGROUND: HIV prevention is a public health priority. Despite progress in recent years, pre-exposure prophylaxis (PrEP) use remains suboptimal especially among groups disproportionately impacted by new HIV diagnoses such as gender and sexual minorities of color. Multiple barriers including a lack of PrEP providers and challenges with attending quarterly monitoring visits contribute to low PrEP uptake and retention. Home-based PrEP (HB-PrEP) services could reduce stigma, increase convenience, expand health system capacity for PrEP care, and improve PrEP retention. OBJECTIVE: Home Option Testing for PrEP (HOT4PrEP) is a hybrid randomized controlled trial (RCT) that aims to examine whether HB-PrEP care is acceptable to PrEP users, feasible to implement in a sexual health clinic setting, and impacts PrEP retention. METHODS: The RCT will recruit 458 persons currently taking or soon to initiate PrEP at a sexual health clinic in Seattle, Washington, and randomize them to continue the standard of care or have the option to use HB-PrEP for 2 of 3 triannual PrEP follow-up visits. Participants in the intervention arm will be sent home kits containing gonorrhea and chlamydia swabs and Tasso devices for blood self-collection. The primary outcome is PrEP retention between groups at 20 months; secondary outcomes include user satisfaction and acceptability, feasibility, self-reported PrEP adherence, and sexually transmitted infection (STI) incidence. Interviews with PrEP users and clinic staff will elucidate barriers and facilitators of implementation. RESULTS: The HOT4PrEP RCT began enrolling in March 2022, was on hold during the height of the US mpox epidemic, then resumed enrollment in December 2022. Of the first 100 enrollees, the median age is 34 years, and most are cisgender gay men (89/100, 89%) with at least some college education (91/100, 91%). Among the 49 participants randomized to the HB-PrEP option, 33 (67%) chose to self-collect samples at home at least once, of whom 27 (82%) successfully returned test kits for HIV and STI testing. Primary PrEP retention and qualitative analyses are ongoing. CONCLUSIONS: Implementation of HB-PrEP into a high-volume sexual health clinic seems to be feasible and acceptable to early RCT enrollees. This strategy has the potential to address individual and systemic barriers associated with initiating and persisting on PrEP, such as increasing sexual health agency and expanding clinical capacity to serve greater numbers of PrEP users. TRIAL REGISTRATION: ClinicalTrials.gov NCT05856942; https://clinicaltrials.gov/study/NCT05856942. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56587.

Clinico-epidemiological characteristics of adolescents and young adults living with HIV in Ghana.

Introduction: sub-Saharan Africa is experiencing a boom in the number of adolescents and young adults living with HIV (AYALHIV). Existing HIV intervention programs are mainly for children and adults living with HIV, with little attention paid to AYALHIV. Characterizing this population is necessary for planning, and designing, AYALHIV-centered HIV intervention programs. Methods: a retrospective single-center, hospital-based chart review was conducted at the largest HIV clinic in Ghana. We examined routinely collected data for AYALHIV (aged 10-24 years) on antiretroviral therapy (ART) for at least 1 year and in active care from 1st January to 31st December 2019. Data was collected using a structured data extraction form. The Chi-square and the Student´s t-test were used to compare characteristics between adolescents and young adults. Results: of 252 AYALHIV, 68% (172/252) were adolescents with a median age of 17 years (IQR 13-19); 32% were young adults with a median age of 22 years (IQR: 20-24). Most (56.7% (143/252)) AYALHIV were female. Almost 40% were orphans. Eighty-six percent of AYALHIV had HIV type I infection. The commonest mode of HIV acquisition among adolescents was vertical transmission (70.5%) and that among young adults was via unprotected sex (31.3%). Eighty-eight percent (88%) of AYALHIV were on non-nucleoside reverse transcriptase inhibitors-based regimen. The viral suppression rate among AYALHIV was 78%. Conclusion: the study shows there is a growing population of AYALHIV most of which are adolescents. About two-fifths were orphans. Policymakers and HIV programs should ensure AYALHIV-centred interventions are developed for this vulnerable population.

Associations of Early Prolonged Secondary Amenorrhea in Women With and Without HIV.

Background: The menstrual cycle is a critical indicator of women's health. Early prolonged secondary amenorrhea increases risks for morbidity and mortality. Menstrual cycle research in women with HIV is inconsistent and often lacks an adequate comparison sample. We aimed to determine whether women with HIV have a higher lifetime prevalence of amenorrhea and whether this is independently associated with HIV and/or other biopsychosocial variables. Methods: With data from 2 established HIV cohorts, participants assigned female at birth were eligible if aged ≥16 years, not pregnant/lactating, and without anorexia/bulimia nervosa history. Amenorrhea was defined by self-reported history of (1) no menstrual flow for ≥12 months postmenarche not due to pregnancy/lactation, medications, or surgery or (2) early menopause or premature ovarian insufficiency. Multivariable logistic regression models explored biopsychosocial covariates of amenorrhea. Results: Overall, 317 women with HIV (median age, 47.5 years [IQR, 39.2-56.4]) and 420 women without HIV (46.2 [32.6-57.2]) were included. Lifetime amenorrhea was significantly more prevalent among women with HIV than women without HIV (24.0% vs 13.3%). In the multivariable analysis, independent covariates of amenorrhea included HIV (adjusted odds ratio, 1.70 [95% CI, 1.10-2.64]), older age (1.01 [1.00-1.04]), White ethnicity (1.92 [1.24-3.03]), substance use history (6.41 [3.75-11.1]), and current food insecurity (2.03 [1.13-3.61]). Conclusions: Nearly one-quarter of women with HIV have experienced amenorrhea, and this is associated with modifiable risk factors, including substance use and food insecurity. Care providers should regularly assess women's menstrual health and advocate for actionable sociostructural change to mitigate risks.

HIV-1 Vpr-induced DNA damage activates NF-κB through ATM-NEMO independent of cell cycle arrest.

Lentiviruses encode a number of multi-functional accessory proteins, however, the primary role of the accessory protein Vpr remains unclear. As Vpr engages the host DNA damage response (DDR) at multiple steps, modulation of the DDR is considered central to the function(s) of Vpr. Vpr activates ataxia telangiectasia and Rad3 (ATR)-mediated DDR signaling, resulting in cell cycle arrest. However, the cellular consequences of Vpr-induced DNA damage, and the connection of Vpr-induced DNA damage to other Vpr functions, are unknown. Here, we determined that HIV-1 Vpr-induced DNA damage activates the ATM-NF-κB essential modulator (NEMO) pathway and alters cellular transcription via NF-κB/RelA. Through RNA-sequencing (RNA-seq) of cells expressing Vpr or mutants that separate the ability of Vpr to induce DNA damage from other DDR phenotypes, we identified that Vpr alters the transcriptome independent of cell cycle arrest. In tissue-cultured U2OS cells and primary human monocyte-derived macrophages (MDMs), we showed Vpr activates both ataxia telangiectasia mutated (ATM) and NF-κB/RelA signaling cascades. While inhibition of NEMO did not affect Vpr-induced DNA damage, it prevented NF-κB activation by Vpr, highlighting the importance of NEMO in Vpr-mediated transcriptional reprogramming. Virion-delivered Vpr was sufficient to induce DNA damage and activate ATM-NEMO dependent NF-κB transcription, suggesting that engagement of the DDR and transcriptional changes can occur early during viral replication. Together, our data uncover cellular consequences of Vpr-induced DNA damage and provide a mechanism for how Vpr activates NF-κB through DNA damage and ATM-NEMO signaling, which occur independent of cell cycle arrest. We propose this is essential to overcoming restrictive environments, such as in macrophages, to enhance viral replication.IMPORTANCEThe HIV accessory protein Vpr is multi-functional and required for viral replication in vivo, yet how Vpr enhances viral replication is unknown. Emerging literature suggests that a conserved function of Vpr is the engagement of the host DNA damage response (DDR). For example, Vpr activates DDR signaling, causes DDR-dependent cell cycle arrest, promotes degradation of various DDR proteins, and alters cellular consequences of DDR activation. However, a central understanding of how these phenotypes connect and how they affect HIV-infected cells remains unknown. Here, we found that Vpr-induced DNA damage alters the host transcriptome by activating an essential transcription pathway, NF-κB. This occurs early during the infection of primary human immune cells, suggesting NF-κB activation and transcriptome remodeling are important for establishing productive HIV-1 infection. Together, our study provides novel insights into how Vpr alters the host environment through the DDR, and what roles Vpr and the DDR play to enhance HIV replication.

The Enigmatic Interplay of Interleukin-10 in the Synergy of HIV Infection Comorbid with Preeclampsia.

Cytokines coordinate the intricate choreography of the immune system, directing cellular activities that mediate inflammation, pathogen defense, pathology and tissue repair. Within this spectrum, the anti-inflammatory prowess of interleukin-10 (IL-10) predominates in immune homeostasis. In normal pregnancy, the dynamic shift of IL-10 across trimesters maintains maternal immune tolerance ensuring fetal development and pregnancy success. Unravelling the dysregulation of IL-10 in pregnancy complications is vital, particularly in the heightened inflammatory condition of preeclampsia. Of note, a reduction in IL-10 levels contributes to endothelial dysfunction. In human immunodeficiency virus (HIV) infection, a complex interplay of IL-10 occurs, displaying a paradoxical paradigm of being immune-protective yet aiding viral persistence. Genetic variations in the IL-10 gene further modulate susceptibility to HIV infection and preeclampsia, albeit with nuanced effects across populations. This review outlines the conceptual framework underlying the role of IL-10 in the duality of normal pregnancy and preeclampsia together with HIV infection, thus highlighting its regulatory mechanisms and genetic influences. Synthesizing these findings in immune modulation presents avenues for therapeutic interventions in pregnancy complications comorbid with HIV infection.