Geospatial pattern of HIV seropositivity and its predictors among women in Ethiopia. A spatial and multiscale geographically weighted regression analysis.

BACKGROUND: Although promising efforts have been made so far, HIV remains a public health concern. Women in Ethiopia are disproportionately affected by HIV, accounting for a majority of new infections and AIDS-related deaths. However, the geospatial distribution of HIV among women in Ethiopia is not well understood, making it challenging to develop geographically targeted measures. Besides, to accelerate the pathway of decreasing HIV prevalence and plan geographically specific interventions, understanding the geospatial distribution of HIV seropositivity and its predictors among women plays a significant role. METHODS: A spatial and multiscale geographically weighted regression analysis was conducted using the 2016 EDHS dataset, comprising 14,778 weighted samples of women in the reproductive age group. The EDHS sample underwent two-stage stratification and selection. The data were extracted between October 18 and 30, 2023. Non-spatial analysis was carried out using STATA version 17. Additionally, ArcGIS Pro and Sat Scan version 9.6 were used to visually map HIV seropositivity. Global Moran's I was computed to evaluate the distribution of HIV seropositivity. The Getis-Ord Gi* spatial statistic was utilized to identify significant spatial clusters of cold and hot spot areas. Geographically weighted regression analysis was subsequently performed to identify significant predictors of HIV seropositivity. Significance was established at a P-value <0.05 throughout all statistical analyses. RESULTS: HIV seropositivity among women in Ethiopia is distributed non-randomly (Global Moran's I = 0.16, p-value <0.001 and Z-score = 7.12). Significant hotspot clustering of HIV seropositivity was found in the Addis Ababa, Harari, Dire Dawa, and Gambela region. Poor wealth index, being divorced and widowed, having more than one sexual partner, and early first sexual experience (<15 years) were found to be predictors of geographical variation of HIV seropositivity among women. CONCLUSION: HIV seropositivity among women in Ethiopia varies geographically. Thus, deploying additional resources in high hotspot regions is recommended. Programs should focus on improving the economic empowerment of women to prevent the from engaging in risky sexual behaviors. Furthermore, comprehensive sex education programs in schools and community settings regarding the consequences of early first sexual debut might play a role in reducing HIV seropositivity among women in Ethiopia.

"First was to sit down and bring our minds together". A qualitative study on safer conception decision-making among HIV sero-different couples in Zimbabwe.

Decision-making on childbearing and safer conception use in HIV sero-different couples involves an intricate balance of individual desires and perceived HIV acquisition risk. This paper addresses an important knowledge gap regarding HIV sero-different couples' considerations and the relationship and power dynamics involved when deciding to use a safer conception method. Between February and June 2019, we conducted semi-structured in-depth interviews among 14 men and 17 women, representing 17 couples, who exited the SAFER study - a pilot study assessing the feasibility, acceptability and cost-effectiveness of a safer conception programme for HIV sero-different couples in Zimbabwe. All couples in SAFER were provided with a choice of safer conception methods and were followed for up to 12 months of pregnancy attempts and 3 months following pregnancy. While couples generally perceived their safer conception discussions to be easy and consensus-driven, the decision-making process also involved complex gender dynamics and trade-offs in relationship power, which resulted in differing interpretations of what constituted a joint or shared couple decision. Participants regarded effective couple communication as an essential component of and precursor to good safer conception conversations and requested additional training in couple communication. Couples relied on information from healthcare providers to kickstart their safer conception discussions. Safer conception programmes should address relationship power imbalances, promote effective couple communication and offer healthcare provider support to enable HIV sero-different couples to make informed choices about conception in a manner that upholds their safety and reproductive autonomy.

Our study explored how HIV sero-different couples in Zimbabwe made decisions on the use of safer conception methods. We interviewed 14 men and 17 women who participated in the SAFER study ­ a pilot study looking at how feasible, acceptable and cost-effective a safer conception programme for HIV sero-different couples is in Zimbabwe. We sought to understand the relationship dynamics, considerations and power trade-offs involved in choosing a safer conception method. Couples reported that their conversations about safer conception were easy and agreeable. At the same time, we found that both gender norms and HIV status shaped the couples' decision-making process, with male gender and partners with an HIV-negative status often having more influence in the final decision of which method to use. Effective couple communication was deemed crucial to support safer conception conversations, with participants requesting additional training in this area. The findings emphasise the importance of providing safer conception methods in a context that addresses power disparities, fosters good communication and includes healthcare providers' support to uphold HIV sero-different couples' reproductive rights and help them achieve their reproductive goals.

Determinants of psychological distress among individuals who are aware of their HIV serostatus in South Africa: findings from the 2017 national HIV prevalence, incidence, behavior, and communication survey.

Introduction: Psychological distress is a growing public health challenge among people living with HIV. This study investigated the prevalence of psychological distress among individuals who know their HIV positive or negative serostatus in South Africa using 2017 data from a nationwide cross-sectional household-based population survey. Methods: The data for this secondary analysis was collected using a multi-stage stratified cluster randomized sampling design. Multivariable backward stepwise generalized linear regression models were fitted to determine factors associated with psychological distress as measured by the Kessler Scale (K10) among HIV-positive and HIV-negative individuals who know their serostatus in South Africa. Results: Of 18,662 participants, psychological distress was 27.4% (95% CI: 25.3-29.7) among those HIV-positive and 20.1% (95% C: 18.8-21.4) among those HIV-negative. The odds of psychological distress were significantly higher among HIV-positive individuals who rated their health as fair/poor [AOR = 1.22 (95% CI: 1.09-1.35), p < 0.001], and the odds were lower among those residing in rural formal/farm areas [AOR = 0.85 (95% CI: 0.78-0.93), p < 0.001], and those with tertiary education level [AOR = 0.88 (95% CI: 0.78-0.99), p = 0.033]. The odds of psychological distress in HIV-negative individuals were significantly higher among females than males [AOR = 1.09 (95% CI: 1.05-1.14), p < 0.001], high-risk alcohol drinkers [AOR = 1.26 (95% CI: 1.02-1.57), p = 0.035] and hazardous alcohol drinkers [AOR = 1.09 (95% CI: 1.01-1.18), p = 0.028] than abstainers and those who rated their health as fair/poor rather than excellent/good [AOR = 1.18 (95% CI: 1.10-1.26), p < 0.001]. Conclusion: The study underscores the importance of addressing, alcohol misuse and socio-structural inequalities linked to gender and race-based disparities, such as low educational attainment and unemployment, as critical factors associated with psychological distress in the study population.

Factors associated with PrEP-era HIV seroconversion in a 4-year U.S. national cohort of n = 6059 sexual and gender minority individuals who have sex with men, 2017-2022.

INTRODUCTION: Community-based cohort studies of HIV seroconversion can identify important avenues for enhancing HIV prevention efforts in the era of pre-exposure prophylaxis (PrEP). Within individuals, one can assess exposure and outcome variables repeatedly and with increased certainty regarding temporal ordering. This cohort study examined the association of several risk factors with subsequent HIV seroconversion. METHODS: We report data from a 4-year study (2017-2022) of 6059 HIV seronegative sexual and gender minority individuals who have sex with men who had indications for-, but were not using-, PrEP at enrolment. Participants completed repeat exposure assessments and self-collection of biospecimens for HIV testing. We examined the roles of race and ethnicity, socio-economic status, methamphetamine use and PrEP uptake over the course of follow-up in relation to HIV seroconversion. RESULTS: Over 4 years, 303 of the participants seroconverted across 18,421 person-years (incidence rate = 1.64 [95% CI: 1.59-1.70] per 100 person-years). In multivariable discrete-time survival analysis, factors independently associated with elevated HIV seroconversion risk included being Black/African American (adjusted risk ratio [aRR]: 2.44, 1.79-3.28), Hispanic/Latinx (1.53, 1.19-1.96), housing instability (1.58, 1.22-2.05) and past year methamphetamine use (3.82, 2.74-5.33). Conversely, time since study enrolment (24 vs. 12 months, 0.67, 0.51-0.87; 36 months, 0.60, 0.45-0.80; 48 months, 0.48, 0.35-0.66) and higher education (master's degree or higher vs. less than or equal to high school, 0.36, 0.17-0.66) were associated with reduced seroconversion risk. Compared to non-PrEP users in the past 2 years without a current clinical indication, those who started PrEP but then discontinued had higher seroconversion risk, irrespective of clinical indication (3.23, 1.74-6.46) or lack thereof (4.30, 1.85-9.88). However, those who initiated PrEP in the past year (0.14, 0.04-0.39) or persistently used PrEP in the past 2 years (0.33, 0.14-0.74) had a lower risk of seroconversion. Of all HIV seroconversions observed during follow-up assessments (12, 24, 36 and 48 months), methamphetamine was reported in the 12 months prior 128 (42.2%) times (overall). CONCLUSIONS: Interventions that acknowledge race and ethnicity, economic variables such as education and housing instability, and methamphetamine use are critically needed. Not only are interventions to engage individuals in PrEP care needed, but those that retain them, and re-engage those who may fall out of care are essential, given the exceptionally high risk of seroconversion in these groups.

Viral load suppression and its predictor among HIV seropositive people who receive enhanced adherence counseling at public health institutions in Bahir Dar, Northwest Ethiopia. Retrospective follow-up study.

BACKGROUND: For those HIV seropositive people with high viral loads, the World Health Organization recommends more counseling before changing ART regimens. A high viral load can lead to increased HIV transmission and lower survival rates. Clients with viral loads above 1000 copies/mL should receive enhanced adherence counseling for 3-6 months before switching. Despite enhanced adherence counseling programs, most countries struggle with viral load suppression. Little is known about viral load suppression in Ethiopia and the research area after counseling. OBJECTIVE: This study aims to assess viral load suppression and its predictors among HIV-positive individuals receiving enhanced adherence counseling in Bahir Dar, Northwest Ethiopia, in 2022. METHODS: An institution-based retrospective follow-up study was conducted among randomly selected 546 clients on Enhanced Adherence Counseling at public health facilities in Bahir Dar city. The Epicollect5 mobile application was used to collect the data, which was then exported to Stata version 14 for analysis. A Log-Binomial regression model was fitted for each explanatory variable. Variables having a p-value <0.25 in bivariate analysis were entered into a multivariable Log-Binomial regression model. Finally, an adjusted risk ratio with a 95% confidence interval and a p-value <0.05 was used to measure the strength of the prediction. RESULTS: Following enhanced adherence counseling, 312 (57.1%) people had their viral load suppressed. Absence of recurrent OI (ARR 1.40; CI 1.03-1.91), EAC stay less than 3 months (ARR 1.54; CI 1.19-1.99), EAC stay 3-6 months (ARR 1.38; CI 1.12-1.69), once-daily ARV dose regimen (ARR 1.28; CI 1.03-1.58), baseline viral load of 2879.00 copies/ml (ARR 1.30, CI 1.06-1.60), being orthodox Tewahido Christian (ARR 0.37; CI 0.18-0.75) were significant predictors of viral load suppression after Enhanced Adherence Counseling. CONCLUSION AND RECOMMENDATION: Most importantly, this study found that most people had suppressed viral loads after receiving enhanced adherence counseling. Significant predictors of viral load suppression included recurrent OI, length of stay on EAC, daily ARV dosing regimen, baseline viral load, and religion. Clients with a high baseline viral load and those who experience recurring opportunistic infections should get extra care during EAC sessions.

Kinetic coevolutionary models predict the temporal emergence of HIV-1 resistance mutations under drug selection pressure.

Drug resistance in HIV type 1 (HIV-1) is a pervasive problem that affects the lives of millions of people worldwide. Although records of drug-resistant mutations (DRMs) have been extensively tabulated within public repositories, our understanding of the evolutionary kinetics of DRMs and how they evolve together remains limited. Epistasis, the interaction between a DRM and other residues in HIV-1 protein sequences, is key to the temporal evolution of drug resistance. We use a Potts sequence-covariation statistical-energy model of HIV-1 protein fitness under drug selection pressure, which captures epistatic interactions between all positions, combined with kinetic Monte-Carlo simulations of sequence evolutionary trajectories, to explore the acquisition of DRMs as they arise in an ensemble of drug-naive patient protein sequences. We follow the time course of 52 DRMs in the enzymes protease, RT, and integrase, the primary targets of antiretroviral therapy. The rates at which DRMs emerge are highly correlated with their observed acquisition rates reported in the literature when drug pressure is applied. This result highlights the central role of epistasis in determining the kinetics governing DRM emergence. Whereas rapidly acquired DRMs begin to accumulate as soon as drug pressure is applied, slowly acquired DRMs are contingent on accessory mutations that appear only after prolonged drug pressure. We provide a foundation for using computational methods to determine the temporal evolution of drug resistance using Potts statistical potentials, which can be used to gain mechanistic insights into drug resistance pathways in HIV-1 and other infectious agents.

Secondary syphilis presenting with alopecia and leukoderma in a stable HIV-positive patient in a resource-limited setting: a case report.

BACKGROUND: Syphilis is an infection caused by the bacteria Treponema pallidum. It is mainly transmitted through oral, vaginal and anal sex, in pregnancy and through blood transfusion. Syphilis develops in primary, secondary, latent and tertiary stages and presents with different clinical features at each stage. Infected patients can remain asymptomatic for several years and, without treatment, can, in extreme cases, manifest as damage in several organs and tissues, including the brain, nervous tissue, eyes, ear and soft tissues. In countries with a high human immunodeficiency virus (HIV) burden, syphilis increases the risk of HIV infections. We report the case of a young HIV-positive black woman who presented with alopecia and hypopigmentation as features of secondary syphilis. CASE PRESENTATION: A virologically suppressed 29-year-old woman on Anti-retroviral Therapy (ART) presented with a short history of generalized hair loss associated with a non-itchy maculopapular rash and skin depigmentation on the feet. Limited laboratory testing confirmed a diagnosis of secondary syphilis. She was treated with Benzathine Penicillin 2.4MU. After receiving three doses of the recommended treatment, the presenting features cleared, and the patient recovered fully. CONCLUSION: This case demonstrates the importance of a high index of clinical suspicion and testing for syphilis in patients presenting with atypical clinical features of secondary syphilis, such as hair loss and hypopigmentation. It also highlights the challenges in diagnosing and clinically managing syphilis in a resource-limited setting.

Violencia en pareja en personas seropositivas: una revisión sistemática / Violência por parceiro íntimo em pessoas soropositivas: uma revisão sistemática / Partner violence in HIV-positive people: a systematic review

El presente trabajo tiene como objetivo, caracterizar la violenciaen pareja en personas con seropositividad (prevalencia,tipos de acciones violentas, variables de riesgo/ protectorasy consecuencias), para lo cual se realizó una revisión sistemáticaa través del protocolo PRISMA. La búsqueda de artículos serealizó en Scopus, Web of Science, Eric, Scielo y Pubmedpublicados hasta 2021. Se encontraron 113 artículos, de loscuales 22 cumplieron con los criterios de elegibilidad. Losresultados indican que la violencia en pareja en personasseropositivas, además de manifestarse de manera física,psicológica, patrimonial, sexual y verbal, se puede presentar através del uso del VIH para ejercer la violencia. La prevalenciavaría en función del contexto geográfico en un intervalo del19,6% al 43,1%; la cual es superior en población migrantey en hombres que tienen sexo con hombres (HSH) mujeresseropositivas, parejas no heterosexuales y en parejas en la queambos miembros son seropositivos. Las variables de riesgo/protectoras identificadas se asociaron con las dimensiones:informativas, motivacionales, de habilidades conductuales,sociodemográficas, culturales, de salud, sociofamiliares ypolíticas. Asimismo, se evidenciaron consecuencias sociales,económicas y de salud.(AU)

The objective of this work is to characterize partner violencein people with seropositivity (prevalence, types of violentactions, risk/protective variables, and consequences), for whicha systematic review was carried out through the PRISMAprotocol. The search for articles was carried out in Scopus,Web of Science, Eric, Scielo and Pubmed published up to 2021. 113 articles were found, of which 22 met the eligibilitycriteria. The results indicate that intimate partner violencein seropositive people, in addition to manifesting itself ina physical, psychological, patrimonial, sexual, and verbalway, can be presented using HIV to exercise violence. Theprevalence varies depending on the geographical contextin a range from 19.6% to 43.1%, which is higher in themigrant population and in men who have sex with men(MSM), seropositive women, non-heterosexual couples andin couples in which both members are seropositive. Therisk/protective variables identified were associated with thedimensions: informational, motivational, behavioral skills,sociodemographic, cultural, health, socio-family and political.Likewise, social, economic and health consequences wereevidenced.(AU)

O objetivo deste trabalho é caracterizar a violência conjugalem pessoas com soropositividade (prevalência, tipos de açõesviolentas, variáveis de risco/proteção e consequências), paraa qual foi realizada uma revisão sistemática por meio doprotocolo PRISMA. A busca de artigos foi realizada no Scopus,Web of Science, Eric, Scielo e Pubmed publicados até 2021.Foram encontrados 113 artigos, dos quais 22 atenderamaos critérios de elegibilidade. Os resultados indicam que aviolência por parceiro íntimo em pessoas soropositivas, alémde se manifestar de forma física, psicológica, patrimonial,sexual e verbal, pode se apresentar por meio do uso do HIVpara exercer a violência. A prevalência varia de acordo como contexto geográfico em uma faixa de 19,6% a 43,1%; queé maior na população migrante e em homens que fazemsexo com homens (HSH), mulheres soropositivas, casais nãoheterossexuais e em casais em que ambos os membros sãosoropositivos. As variáveis de risco/proteção identificadasforam associadas às dimensões: informacional, motivacional,habilidades comportamentais, sociodemográficas, culturais,de saúde, sociofamiliares e políticas. Da mesma forma, foramevidenciadas consequências sociais, econômicas e de saúde.(AU)

The lived experiences of HIV-positive women in rural Zimbabwe: A qualitative focus group study.

BACKGROUND:  The study explored and described the meaning attached to the lived experiences of women living with human immunodeficiency virus (HIV) in the rural context of Zimbabwe. Stigma and discrimination negatively impact one's ability to perform the expected social roles, the quality of life, and the efforts to prevent the spread of HIV and acquired immunodeficiency syndrome (AIDS) and reduce HIV-related mortality. Thus, the study aims to understand the meaning attached to the lived experiences of HIV-positive women living in rural areas or villages of Matabeleland South province in Zimbabwe. METHODS:  The study used a qualitative, descriptive, and exploratory design. Four focus group discussions were conducted with 24 HIV-positive rural women living in Matabeleland South province, Zimbabwe. An Interpretative Phenomenological Analysis (IPA) was adopted to explore and describe the meaning attached to the lived experiences of women living with HIV. RESULTS:  Two interconnected themes were identified in the analysis with their sub-themes. These were: (1) struggle for social belonging, with subthemes - loss of social belonging and reduced access to community-based empowerment opportunities and (2) struggle for maintaining the quality of life with subthemes - lack of need-based community healthcare and food insecurity. CONCLUSION:  Being a woman living with HIV in rural Zimbabwe means a perpetual struggle to maintain one's humanness and quality of life.Contribution: This study's results will support the efforts of the Zimbabwean government to improve the quality of life of HIV-positive women living in rural areas.

The development, evaluation, performance, and validation of micro-PCR and extractor for the quantification of HIV-1 &-2 RNA.

HIV infection has been a global public health threat and overall reported ~ 40 million deaths. Acquired immunodeficiency syndrome (AIDS) is attributed to the retroviruses (HIV-1/2), disseminated through various body fluids. The temporal progression of AIDS is in context to the rate of HIV-1 infection, which is twice as protracted in HIV-2 transmission. Q-PCR is the only available method that requires a well-developed lab infrastructure and trained personnel. Micro-PCR, a portable Q-PCR device, was developed by Bigtec Labs, Bangalore, India. It is simple, accurate, fast, and operationalised in remote places where diagnostic services are inaccessible in developing countries. This novel micro-PCR determines HIV-1 and HIV-2 viral load using a TruePrep™ extractor device for RNA isolation. Five ml blood samples were collected at the blood collection centre at AIIMS, New Delhi, India. Samples were screened for serology, and a comparison of HIV-1/2 RNA was done between qPCR and micro-PCR in the samples. The micro-PCR assay of HIV-RNA has compared well with those from real-time PCR (r = 0.99, i < 0.002). Micro-PCR has good inter and intra-assay reproducibility over a wide dynamic range (1.0 × 102-1.0 × 108 IU/ml). The linear dynamic range was 102-108 IU/ml. The clinical and analytical specificity of the assay was comparable, i.e., 100%. Intra-assay and inter-assay coefficients of variation ranged from 1.17% to 3.15% and from 0.02% to 0.46%, respectively. Moreover, due to the robust, simple, and empirical method, the Probit analysis has also been done for qPCR LODs to avoid uncertainties in target recoveries. The micro-PCR is reliable, accurate, and reproducible for early detection of HIV-1 and HIV-2 viral loads simultaneously. Thus, it can easily be used in the field and in remote places where quantification of both HIV-1/2 is not reachable.

Epidemiological and virological surveillance of the prevention of mother-to-child transmission of HIV among pregnant women in Togo.

BACKGROUND: In 2015, Togo introduced the "test-and-treat" strategy for the prevention of mother-to-child transmission (PMTCT) of HIV. Pediatric HIV infection remains a public health problem in Togo, with a mother-to-child transmission (MTCT) rate of 3.6% in 2020. This study aimed to estimate cases of HIV seroconversion during pregnancy and to identify pregnant women at high risk of transmitting HIV to their children in Lomé, Togo. METHODS: A descriptive cross-sectional study was carried out from 18 March to 22 May 2022 among women who had given birth in five maternity units providing PMTCT services in Lomé. Umbilical cord blood samples were taken from the maternal side by midwives after delivery. HIV serology was performed in the laboratory using the Alere™ HIV Combo SET and First Response HIV 1-2. Card Test version 2.0. A sample was considered positive if both tests were positive. The HIV-1 viral load in HIV-1-positive samples was measured using Cobas/Roche 4800 equipment. Information on the women was extracted from maternal antenatal records and antenatal consultation registers. RESULTS: A total of 3148 umbilical cord blood samples (median maternal age: 28 years (interquartile range [24-32]) were collected. Among them, 99.3% (3145/3148) had presented for at least one antenatal clinic visit before giving birth, and 78.7% (2456/3122) had presented for at least four visits. One hundred and twenty-one (121) cord samples were HIV-1 positive, representing a seroprevalence of 3.8% (95% CI = [3.2-4.6]). Among them, 67.8% (82/121) were known HIV-positive before the current pregnancy, 29.7 (36/121) were diagnosed as HIV-positive at the antenatal visits and 2.5% (3/121) were diagnosed as HIV-positive in the delivery room. Of the HIV-positive women, 85.9% (104/121) were on ARV treatment before delivery. The viral load was < 1000 copies/ml in 97.5% (118/121) cases. CONCLUSION: This study explored the virologic and epidemiological aspects of HIV among pregnant women in Togo. The results show significant viral suppression at delivery in women ART. Surveillance based on umbilical cord blood specimen screening is an interesting approach for monitoring the effectiveness of PMTCT programmes.

Receptor transfer between immune cells by autoantibody-enhanced, CD32-driven trogocytosis is hijacked by HIV-1 to infect resting CD4 T cells.

Immune cell phenotyping frequently detects lineage-unrelated receptors. Here, we report that surface receptors can be transferred from primary macrophages to CD4 T cells and identify the Fcγ receptor CD32 as driver and cargo of this trogocytotic transfer. Filamentous CD32+ nanoprotrusions deposit distinct plasma membrane patches onto target T cells. Transferred receptors confer cell migration and adhesion properties, and macrophage-derived membrane patches render resting CD4 T cells susceptible to infection by serving as hotspots for HIV-1 binding. Antibodies that recognize T cell epitopes enhance CD32-mediated trogocytosis. Such autoreactive anti-HIV-1 envelope antibodies can be found in the blood of HIV-1 patients and, consistently, the percentage of CD32+ CD4 T cells is increased in their blood. This CD32-mediated, antigen-independent cell communication mode transiently expands the receptor repertoire and functionality of immune cells. HIV-1 hijacks this mechanism by triggering the generation of trogocytosis-promoting autoantibodies to gain access to immune cells critical to its persistence.

Late presentations and missed opportunities among newly diagnosed HIV patients presenting to a specialty clinic in Lebanon.

Late presentation to medical care of individuals infected with the human immunodeficiency virus (HIV) is linked to poor outcomes and increased morbidity and mortality. Missed opportunities for a prompt diagnosis are frequently reported among late presenters. We aimed to estimate the proportion of late presenters and missed opportunities in diagnosis among newly diagnosed HIV-positive subjects presenting to a specialty clinic in Lebanon. This is a retrospective chart review of all newly diagnosed adult HIV-positive subjects presenting to clinic from 2012 to 2022. Demographic, laboratory, and clinical data were collected at initial HIV diagnosis or presentation to medical care. We defined late presentation as having a CD4 count < 350 or AIDS-defining event regardless of CD4 count. Advanced disease is defined as having a CD4 count below 200 cells/µL or the presence of an AIDS-defining illness, regardless of the CD4 count. A missed opportunity was defined as the presence of an indicator condition (IC) that suggests infection with HIV/AIDS during 3 years preceding the actual HIV diagnosis and not followed by a recommendation for HIV testing. The proportions for demographic, epidemiological, and clinical characteristics are calculated by excluding cases with missing information from the denominator. Our cohort included 150 subjects (92.7% males; 63.6% men who have sex with men (MSM); 33.3% heterosexuals; median age 30.5 years at diagnosis). 77 (51.3%) were late presenters and 53 (35.3% of all subjects, 68.8% of late presenters) had advanced HIV on presentation. Up to 76.5% of late presenters had a presentation with an HIV-related condition at a healthcare provider without getting HIV test within the previous 3 years. The most frequent ICs were weight loss, generalized lymphadenopathy, constitutional symptoms, and chronic idiopathic diarrhea. Overall mortality rate was 4% (6/150 individuals). All-cause mortality among those who presented with AIDS was 15.4% (6/39 subjects). In our setting, late presentations and missed opportunities for HIV diagnosis are common. In the Middle East, AIDS mortality remains high with a large gap in HIV testing. To effectively influence policies, comprehensive analyses should focus on estimating the preventable health and financial burdens of late HIV presentations. Another concern pertains to healthcare providers' attitudes and competencies.

Association between HIV Serostatus and premalignant cervical lesions among women attending a cervical cancer screening clinic at a tertiary care facility in southwestern Uganda: a comparative cross-sectional study.

BACKGROUND: Uganda has approximately 1.2 million people aged 15-64 years living with human immunodeficiency virus (HIV). Previous studies have shown a higher prevalence of premalignant cervical lesions among HIV-positive women than among HIV-negative women. Additionally, HIV-infected women are more likely to have human papilloma virus (HPV) infection progress to cancer than women not infected with HIV. We determined the prevalence of premalignant cervical lesions and their association with HIV infection among women attending a cervical cancer screening clinic at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda. METHODS: We conducted a comparative cross-sectional study of 210 women aged 22-65 years living with HIV and 210 women not living with HIV who were systematically enrolled from March 2022 to May 2022. Participants were subjected to a structured interviewer-administered questionnaire to obtain their demographic and clinical data. Additionally, Papanicolaou smears were obtained for microscopy to observe premalignant cervical lesions. Multivariate logistic regression was performed to determine the association between HIV status and premalignant cervical lesions. RESULTS: The overall prevalence of premalignant cervical lesions in the study population was 17% (n = 72; 95% C.I: 14.1-21.4), with 23% (n = 47; 95% C.I: 17.8-29.5) in women living with HIV and 12% (n = 25; 95% C.I: 8.2-17.1) in women not living with HIV (p < 0.003). The most common premalignant cervical lesions identified were low-grade squamous intraepithelial lesions (LSIL) in both women living with HIV (74.5%; n = 35) and women not living with HIV (80%; n = 20). HIV infection was significantly associated with premalignant lesions (aOR: 2.37, 95% CI: 1.27-4.42; p = 0.007). CONCLUSION: Premalignant cervical lesions, particularly LSILs, were more common in HIV-positive women than in HIV-negative women, highlighting the need to strengthen the integration of cervical cancer prevention strategies into HIV care programs.

Gestational gigantomastia complicated by pseudo-angiomatous stromal hyperplasia - a multidisciplinary management approach.

SUMMARY: Gestational gigantomastia is a rare condition typified by disproportionate bilateral breast enlargement in pregnant women, resulting in skin thinning, ulceration, and bleeding. Less than sixty cases have been documented worldwide, and only one other in South Africa. Pseudo-angiomatous stromal hyperplasia (PASH) is a rare benign proliferation of stromal tissue in a tumorous or diffuse pattern. This, to the best of our knowledge, is the first published case, a 27-year-old human immunodeficiency virus (HIV) positive woman, to present with both conditions concurrently. Medical management with cabergoline was initiated and, seven months post-delivery, a novel Goldilocks mastectomy was performed with acceptable outcomes.

Discovery of low-molecular-weight phenylalanine derivatives as novel HIV capsid modulators with improved antiretroviral activity and metabolic stability.

The HIV capsid (CA) protein is a promising target for anti-AIDS treatment due to its critical involvement in viral replication. Herein, we utilized the well-documented CA inhibitor PF74 as our lead compound and designed a series of low-molecular-weight phenylalanine derivatives. Among them, compound 7t exhibited remarkable antiviral activity with a high selection index (EC50 = 0.040 µM, SI = 2815), surpassing that of PF74 (EC50 = 0.50 µM, SI = 258). Furthermore, when evaluated against the HIV-2 strain, 7t (EC50 = 0.13 µM) demonstrated approximately 14-fold higher potency than that of PF74 (EC50 = 1.76 µM). Insights obtained from surface plasmon resonance (SPR) revealed that 7t exhibited stronger target affinity to the CA hexamer and monomer in comparison to PF74. The potential interactions between 7t and the HIV-1 CA were further elucidated using molecular docking and molecular dynamics simulations, providing a plausible explanation for the enhanced target affinity with 7t over PF74. Moreover, the metabolic stability assay demonstrated that 7t (T1/2 = 77.0 min) significantly outperforms PF74 (T1/2 = 0.7 min) in human liver microsome, exhibiting an improvement factor of 110-fold. In conclusion, 7t emerges as a promising drug candidate warranting further investigation.

Phase 1 trial evaluating safety and pharmacokinetics of HIV-1 broadly neutralizing mAbs 10E8VLS and VRC07-523LS.

BACKGROUNDBroadly neutralizing monoclonal antibodies (bNAbs) represent a promising strategy for HIV-1 immunoprophylaxis and treatment. 10E8VLS and VRC07-523LS are bNAbs that target the highly conserved membrane-proximal external region (MPER) and the CD4-binding site of the HIV-1 viral envelope glycoprotein, respectively.METHODSIn this phase 1, open-label trial, we evaluated the safety and pharmacokinetics of 5 mg/kg 10E8VLS administered alone, or concurrently with 5 mg/kg VRC07-523LS, via s.c. injection to healthy non-HIV-infected individuals.RESULTSEight participants received either 10E8VLS alone (n = 6) or 10E8VLS and VRC07-523LS in combination (n = 2). Five (n = 5 of 8, 62.5%) participants who received 10E8VLS experienced moderate local reactogenicity, and 1 participant (n = 1/8, 12.5%) experienced severe local reactogenicity. Further trial enrollment was stopped, and no participant received repeat dosing. All local reactogenicity resolved without sequelae. 10E8VLS retained its neutralizing capacity, and no functional anti-drug antibodies were detected; however, a serum t1/2 of 8.1 days was shorter than expected. Therefore, the trial was voluntarily stopped per sponsor decision (Vaccine Research Center, National Institute of Allergy and Infectious Diseases [NIAID], NIH). Mechanistic studies performed to investigate the underlying reason for the reactogenicity suggest that multiple mechanisms may have contributed, including antibody aggregation and upregulation of local inflammatory markers.CONCLUSION10E8VLS resulted in unexpected reactogenicity and a shorter t1/2 in comparison with previously tested bNAbs. These studies may facilitate identification of nonreactogenic second-generation MPER-targeting bNAbs, which could be an effective strategy for HIV-1 immunoprophylaxis and treatment.TRIAL REGISTRATIONClinicaltrials.gov, accession no. NCT03565315.FUNDINGDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH.

Implementation of a Pharmacist-Led, Long-Acting, Injectable Cabotegravir/Rilpivirine Program for HIV-1 at Health System-Based Clinics in the New York Metropolitan Area.

Long-acting cabotegravir/rilpivirine (LA-CAB/RPV) is the first complete injectable antiretroviral for patients living with HIV. To facilitate patient access to long-acting injectable treatment, a system-wide, pharmacist-led, LA-CAB/RPV transition program was developed at four health system-based New York clinics. Provider referrals were received across four clinics between January 22nd, 2021, and December 31st, 2022. All referrals were evaluated by a pharmacist for clinical eligibility and medication access. The primary outcome was the treatment retention rate defined as the percentage of patients who remained on LA-CAB/RPV at 3 months post-transition. A total of 171 referrals were received, with 73 patients (43%) initiating LA-CAB/RPV. Baseline demographics included a median age of 38 years, 81% patients were male, 41% were African American, and 49% had commercial insurance coverage. The treatment retention rate was 90% at 3 months post-transition. By the end of the study period, 84% of patients who transitioned remained on LA-CAB/RPV. Treatment was discontinued due to reasons such as viral breakthrough (4%), emergence of mutations (4%), and intolerable side effects (4%). Injection site reactions were commonly reported (51%), but only resulting in treatment discontinuation for one patient. A pharmacist-led program can transition a diverse population of patients living with HIV to LA-CAB/RPV. Results from this study further add to clinical experiences with LA-CAB/RPV, demonstrating real-world treatment retention despite more frequent clinic visits for patients.

Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people with HIV-1 aged ≥ 50 years: week 48 pooled results from the TANGO and SALSA studies.

BACKGROUND: As the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years). METHODS: Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis. RESULTS: Of 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years. CONCLUSIONS: Among individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities. TRIAL REGISTRATION NUMBER: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019).