HIV-negative Counterparts Research Articles

Disparity in receiving destination treatment for heart failure patients according to HIV status

Abstract Background Patients living with HIV (PLWH) are well known to be at higher risk of developing cardiovascular diseases. However, PLWH with end-stage HF (ESHF) might not be considered for definitive treatments equally as their HIV-negative counterparts. Methods National Inpatient Sample (NIS) database was queried to identify ESHF patients hospitalized to receive left ventricular assist device (LVAD) or undergo heart transplantation (HTX). In-hospital outcomes of this population were stratified based on HIV status. Results Weighted data of a total of 16,700 ESHF patients was retrieved, out of which 65 patients (0.2%) had a positive HIV status. Out of 65 PLWH with ESHF, 35 patients (53.8%) received LVAD, and 30 patients (46.1%) received HTX, which were comparable to their HIV-negative counterparts (58.4% and 43.1%, respectively). Although PLWH had a longer length of stay (39.7±35.6 days vs. 49.5±, 42.3 days, p=0.3) and higher hospital charges ($1,458,527±$ 1,509,873 vs. $1,113,344±$953,830) than HIV negative counterparts, the difference was not statistically significant. Mortality rate did not differ between HF patients based on HIV positive status or the bridge/destination treatment they had received. Conclusions Although the proportion of PLWH with HF who received HTX has decreased over the last few years, the proportion of those who received LVAD has been on a compensatory rise. HIV positive status is not associated with a higher mortality rate but increases the length of stay and hospital charges.

Entangled Connections: HIV and HPV Interplay in Cervical Cancer-A Comprehensive Review.

Cervical cancer (CC) remains a prevalent malignancy and a significant global public health concern, primarily driven by persistent human papillomavirus (HPV) infections. The infectious nature of HPV underscores the preventability of CC through vaccination and screening programs. In addition to HPV, factors such as age, parity, smoking, hormonal contraceptives, and HIV co-infection elevate the risk of CC. HIV-associated immunodeficiency exacerbates susceptibility to infections and cancers, making CC a defining condition for acquired immune deficiency syndrome (AIDS) and one of the most commonly diagnosed cancers among women living with HIV (WLWH). These women face higher risks of HPV exposure due to sexual behavior and often encounter economic, social, and psychological barriers to screening. HIV and HPV co-infection can potentially accelerate CC carcinogenesis, with WLWH typically being diagnosed with CC earlier than their HIV-negative counterparts. Antiretroviral therapy (ART), which reduces AIDS-related mortality, also lowers the risk of invasive CC. The interaction between HIV and HPV is intricate and bidirectional. This summary reviews current evidence on HPV infection and CC in WLWH, highlighting the connections across pathogenesis, prevention, diagnosis, and treatment.

The unmet mental health needs of adolescents with HIV in eastern Tanzania: Experiences of healthcare providers, adolescents, and caregivers.

Adolescents with Human Immunodeficiency Virus (HIV) are at greater risk for mental health problems than their HIV-negative counterparts. However, there is a dearth of evidence on the need for mental health services, including interventions for depression in adolescents with HIV (AWHIV), in most low- and middle-income countries (LMICs). This study's objective was to explore the unmet mental health needs of AWHIV to inform the development and implementation of a psychological intervention for depression in AWHIV in Dar es Salaam, Tanzania. A descriptive phenomenological qualitative study design was used. Consultative meetings with providers and 45 in-depth interviews were conducted with AWHIV, caregivers, and healthcare providers (HCPs) to explore their experiences and unmet mental health needs for AWHIV. Data from the consultative meetings were triangulated to validate the obtained information with those from interviews. Data were organized and managed with the aid of NVIvo-11. The thematic analysis framework guided data analysis. Five major themes emerged: Experience of complex symptoms, unmet need for services, impact of the unmet needs, ways utilized in managing symptoms, and preferred intervention. Complex depressive symptoms expressed as physical, behavioral, or somatic complaints adversely affected ART adherence and academic performance, led to substance use, and compromised overall quality of life in AWHIV. HIV-Care and Treatment Centers (HIV-CTCs) did not conduct formal mental health screenings. Instead, caregivers and HCPs addressed the symptoms of mental health problems with death threats and corporal punishments. No evidence-based depression interventions existed in HIV-CTCs for observed symptoms. This study reports on unmet mental health needs with a clear impact on the lives of AWHIV, which may have significant implications for treatment adherence. There is an urgent need to develop and implement effective and scalable interventions to address these mental health needs.

A New Start with HAART: Evaluating Breast Reconstruction in the Era of Highly Active Antiretroviral Therapy.

As HIV-positive individuals utilizing highly active antiretroviral therapy live longer, the burden of breast cancer increases in the population. Breast reconstruction is an integral aspect of surgical treatment for many patients after a breast cancer diagnosis, prompting this examination of the characteristics and outcomes of breast reconstruction in this growing patient population. Using Merative MarketScan Research Databases, a large multipayer database, HIV-positive adult patients who underwent autologous or implant-based breast reconstruction between 2007 and 2021 were identified using International Classification of Disease codes and Common Procedural Terminology codes. In both HIV-positive and -negative cohorts, patient demographics, procedure-related complications, and postoperative revisions were recorded. Shapiro-Wilk, chi-square, Wilcoxon-Mann-Whitney, and multivariable logistic regression tests were used for statistical analysis. Of 173,421 patients who underwent breast reconstruction, 1816 had an HIV diagnosis. HIV-positive patients were younger (P < 0.001), underwent surgery more recently (P < 0.001), more often underwent immediate breast reconstruction (P < 0.001), and had higher comorbidity levels (P < 0.001). There was a regional variation in which the patient cohorts underwent breast reconstruction. There was no significant difference in overall complication rates between patient groups, but HIV-negative patients more often underwent revision procedures (P = 0.009). When compared to their HIV-negative counterparts, breast reconstruction can be considered safe and efficacious in patients living with HIV. HIV-positive patients are a growing demographic who seek breast reconstruction, and surgeons must continue to further understand the unique implications of breast reconstruction in this population.

Assessing COVID-19 Vulnerability Among HIV-positive Men Who Have Sex With Men in Korea: The Role of Vaccination and Sexual Behaviors.

Comorbidities increase susceptibility to severe coronavirus disease 2019 (COVID-19) infections, but limited information has been published regarding human immunodeficiency virus (HIV) and COVID-19 co-infections. This study explored the relationships among socioeconomic characteristics, sexual behaviors, and COVID-19 infection rates among Korean men who have sex with men (MSM) who are also living with HIV. Data were collected through a web survey aimed at members of the largest gay portal site in Korea, supported by the National Research Foundation of Korea (n=1005). The primary independent variables included COVID-19-related vaccinations and sexual behaviors. The dependent variable was the incidence of COVID-19 infection among respondents during the pandemic. For statistical analysis, hierarchical multiple logistic regression was performed, controlling for potential confounding variables. Model I indicated that older MSM were less likely to contract COVID-19 (adjusted odds ratio [aOR], 0.98; 95% confidence interval [CI], 0.96 to 0.99). Model II demonstrated that HIV-positive MSM were nearly twice as likely to be infected with COVID-19 compared to their HIV-negative counterparts (aOR, 1.97; 95% CI, 1.14 to 3.41). Furthermore, even after accounting for COVID-19 vaccination status in model III, HIV-positive MSM continued to show a higher risk of infection (aOR, 1.93; 95% CI, 1.12 to 3.35). The findings of this study indicate that HIV-positive MSM are at an increased risk of contracting COVID-19, even when their vaccination status is considered. Therefore, it is essential to prioritize the prevention of COVID-19 infections in HIV-positive individuals by administering appropriate antiretroviral therapy and ensuring adherence to public health guidelines.

Chronic immune activation and accelerated immune aging among HIV-infected adults receiving suppressive antiretroviral therapy for at least 12 years in an African cohort

BackgroundHIV-associated alterations innate and adaptive immune cell compartments are reminiscent of the process of immune aging. ObjectivesWe described immune aging phenotypes among ART-treated HIV-infected adults relative to age-matched HIV-negative counterparts. MethodsIn a cross-sectional comparative study of HIV-infected adults with CD4≥500 cells/μl after at least 12 years of suppressive ART and age-and-gender-matched HIV-negative individuals, immune activation and immune aging phenotypes were measured, using multi-color flowcytometry. ResultsART-treated HIV-infected individuals had higher body mass index (P = 0.004), waist-hip circumference (P = 0.041), hip circumference (P < 0.001), and diastolic blood pressure (P = 0.012) and immune activation (CD4+CD38+HLADR+; median 4.15,IQR(1.030,14.6)] relative to the HIV-negative age-matched individuals [median 3.14,IQR(1.030, 6.68)]; P=0.0034. Immune aging markers [CD4+CD57+T-cells; median 13.00 IQR (0.45,64.1)] were higher among HIV-infected ART-treated adults<50 years relative to HIV-negative<50 years[median 8.020,IQR(0.004,21.2)]; P=0.0010. Naïve CD4 T-cells, Central memory CD4 T-cells, Terminal Effector Memory T cells (TEMRA: CD27−CD45RA + CCR7-) and immune senescence CD4/CD8+CD28-/CD57+ T-cells were similar among ART-treated HIV-infected individuals<45 years relative to 60 years-and-older HIV-negative counterparts≥; p = 0.0932, p = 0.05357, p = 0.0950 and p = 0.5714 respectively. ConclusionART-treated adults are immunologically two decades older than their HIV-negative counterparts. Accelerated immune aging among individuals aging with HIV underscores the need for an HIV cure to avert the unprecedented complications of accelerated immune senescence and the associated NCD risk in African settings with protracted exposure to endemic co-infections.

Epidemiology and treatment outcomes of recurrent tuberculosis in Tanzania from 2018 to 2021 using the National TB dataset.

Patients with recurrent TB have an increased risk of higher mortality, lower success rate, and a relatively feeble likelihood of treatment completion than those with new-onset TB. This study aimed to assess the epidemiology of recurrent TB in Tanzania; specifically, we aim to determine the prevalence of TB recurrence and factors associated with unfavourable treatment outcomes among patients with recurrent TB in Tanzania from 2018 to 2021. In this cross-sectional study, we utilized Tanzania's routinely collected national TB program data. The study involved a cohort of TB patients over a fixed treatment period registered in the TB and Leprosy case-based District Health Information System (DHIS2-ETL) database from 2018 to 2021 in Tanzania. We included patients' sociodemographic and clinical factors, facility characteristics, and TB treatment outcomes. We conducted bivariate analysis and multivariable multi-level mixed effects logistic regression of factors associated with TB recurrence and TB treatment outcomes to account for the correlations at the facility level. A purposeful selection method was used; the multivariable model included apriori selected variables (Age, Sex, and HIV status) and variables with a p-value <0.2 on bivariate analysis. The adjusted odds ratio and 95% confidence interval were recorded, and a p-value of less than 0.05 was considered statistically significant. A total of 319,717 participants were included in the study; the majority were adults aged 25-49 (44.2%, n = 141,193) and above 50 years (31.6%, n = 101,039). About two-thirds were male (60.4%, n = 192,986), and more than one-fifth of participants (22.8%, n = 72,396) were HIV positive. Nearly two in every hundred TB patients had a recurrent TB episode (2.0%, n = 6,723). About 10% of patients with recurrent TB had unfavourable treatment outcomes (9.6%, n = 519). The odds of poor treatment outcomes were two-fold higher for participants receiving treatment at the central (aOR = 2.24; 95% CI 1.33-3.78) and coastal zones (aOR = 2.20; 95% CI 1.40-3.47) than the northern zone. HIV-positive participants had 62% extra odds of unfavourable treatment outcomes compared to their HIV-negative counterparts (aOR = 1.62; 95% CI 1.25-2.11). Bacteriological TB diagnosis (aOR = 1.39; 95% CI 1.02-1.90) was associated with a 39% additional risk of unfavourable treatment outcomes as compared to clinical TB diagnosis. Compared to community-based DOT, patients who received DOT at the facility had 1.39 times the odds of poor treatment outcomes (aOR = 1.39; 95%CI 1.04-1.85). TB recurrence in Tanzania accounts for 2% of all TB cases, and it is associated with poor treatment outcomes. Unfavourable treatment outcomes were recorded in 10% of patients with recurrent TB. Poor TB treatment outcome was associated with HIV-positive status, facility-based DOT, bacteriologically confirmed TB and receiving treatment at the hospital level, differing among regions. We recommend post-treatment follow-up for patients with recurrent TB, especially those coinfected with HIV. We also propose close follow-up for patients treated at the hospital facility level and strengthening primary health facilities in TB detection and management to facilitate early treatment initiation.

Oral health-related quality of life among people living with HIV and HIV-negative adults in Kigali, Rwanda: a comparative cross-sectional study

BackgroundAssessing health-related quality of life has become integral to people living with HIV (PLHIV) follow-up. However, there is a lack of data regarding the impact of oral health on quality of life, known as Oral health-related quality of life (OHRQoL) among PLHIV compared to HIV-negative individuals in Rwanda.AimThe study aimed to assess OHRQoL among PLHIV compared to HIV-negative counterparts in Kigali, Rwanda.MethodsThe Oral Health Impact Profile short version (OHIP-14) questionnaire was interviewer-administered to 200 PLHIV and 200 HIV-negative adults (≥ 18 years old) at an HIV clinic of Kigali Teaching Hospital (CHUK). Socio-demographic characteristics, including age, sex, occupation, and socioeconomic status (SES) of participants, were collected using a survey questionnaire. A 4-point Likert scale was used to assess the frequency of oral impacts for all 14 items within 7 domains of the OHIP tool. The descriptive statistics were used to see frequencies and percentages of OHRQoL among PLHIV and HIV-negative persons, respectively. The Chi-square test was used to determine the association of OHRQoL with caries (DMFT) and periodontal disease (CPITN) among PLHIV compared to HIV-negative individuals.ResultsThe results revealed a higher prevalence of PLHIV with poor OHRQoL than HIV-negative individuals in 5 domains and almost all items of OHIP-14 except for the OHIP 3 (found it uncomfortable to eat any foods because of problems with teeth or mouth) and OHIP-14 (being totally unable to function because of problems with teeth or mouth). The findings showed statistically significant results (p ≤ 0.05) for the OHIP1 item “trouble pronouncing any word,” with a prevalence of 2.5% (n = 11) and 2.25% (n = 9) in PLHIV and HIV-negative, respectively. Also, PLHIV had a significantly higher prevalence, 2.75% (n = 11) for the OHIP 13 item “life not satisfying due to teeth and mouth problems compared to HIV-negative individuals 2% (8) p ≤ 0.05. Moreover, dental caries was significantly associated with poor OHRQoL among PLHIV and HIV-negative adults and for all 14 items of the OHIP tool. Periodontal disease was not significantly associated with OHRQoL among PLHIV and HIV-negative adults.ConclusionThis study revealed poor OHRQoL among PLHIV compared to HIV-negative adults. There is a need for further longitudinal studies to investigate the OHRQoL in Rwanda, especially among PLHIV. It is essential to include oral health care as one of the components of the medical health care programs for PLHIV in Rwanda.

No Evidence for an Association of HIV and Antiviral Treatment With Changes in Framingham Cardiovascular Risk Score in the Ndlovu Cohort Study.

HIV and antiretroviral therapy (ART) have been associated with increased cardiovascular disease (CVD) risk in high-income countries. The authors studied the longitudinal association between HIV and ART and nonlaboratory Framingham Risk Score (FRS) in a middle-income country. This longitudinal analysis of the NCS (Ndlovu Cohort Study), South Africa used baseline to 36-month follow-up data. Demographics, HIV, ART status, and cardiometabolic measures were obtained. FRS was used as a CVD risk measure. Through linear mixed models, FRS trends over time and the association with HIV were studied. Analysis included 1136 participants, with 609 (54%) having HIV, and 495 (81%) taking ART. At baseline, 9.8% of participants had a high FRS. People living with HIV (PLHIV) had a 3.2% lower FRS than HIV-negative participants (P<0.001). FRS increased similarly for both groups over time. Other factors associated with FRS were secondary and higher education (ß value: -0.075, P<0.001; ß value: -0.084, P<0.001) and alcohol consumption (ß value: 0.011, P<0.001). CVD risk increased for all participants over 36 months, suggesting classic risk factors rather than HIV status or ART to be drivers of CVD risk. People living with HIV had a significantly lower FRS than their HIV-negative counterparts, possibly related to HIV itself or a more frequent interaction with healthcare services. No association of HIV and ART with changes in FRS over 36 months was observed, suggesting the need for research using clinical endpoints to elucidate the effects of HIV and ART on CVD risk. Population-based prevention of CVD risk factors in sub-Saharan Africa is warranted, regardless of HIV status.

Supportive Care for People Living with HIV and Cancer in the United States

People with HIV (PWH) in the United States (US) are living longer and are aging into demographic groups in which chronic conditions such as cancer, specifically non-AIDS defining cancers, more commonly occur. Not only do PWH have higher rates of these cancers, but they are also more likely to experience higher, stage-adjusted, cancer-specific mortality compared to their HIV-negative counterparts. One important contributing factor is the disparity in the type of treatment offered to cancer patients with HIV. In a study comparing the use of palliative care among patients with cancer living with and without HIV in the US, researchers found that among those diagnosed with early stage-cancer, PWH had 96% higher odds of receiving palliative care versus those without HIV. On the other hand, among those diagnosed with stage 4 cancer, PWH had 30% lower odds of receiving palliative care compared to their HIV-negative counterparts. The investigators also showed that PWH who did not receive palliative care had 48% lower odds of receiving curative treatment. As for those who did receive palliative care, they were also less likely to receive curative treatment compared to those without HIV, suggesting that PWH were receiving palliative care in lieu of curative treatment. These findings reinforce prior data that curative treatment is not routinely offered to PWH in an equitable way and underscore the importance of developing efforts to improve outcomes in this marginalized population.

Human Papillomavirus Types and Cervical Cancer Screening among Female Sex Workers in Cameroon.

Female sex workers (FSWs) are at high risk for sexually transmitted infections (STIs), including infection with human papillomavirus (HPV) and cervical cancer due to occupational exposure. The objective of this study was to estimate the prevalence of HPV, HPV types, and precancerous lesions of the cervix among FSWs in Cameroon. In this cross-sectional study, FSWs in Cameroon aged 30 years and above were screened for cervical cancer using high-risk HPV testing and genotyping and visual inspection with acetic acid and Lugol's iodine (VIA/VILI) enhanced using digital cervicography (DC) simultaneously. Those who were positive for VIA/VILI-DC were provided treatment with thermal ablation (TA) immediately for cryotherapy/TA-eligible lesions while lesions meeting the criteria for large loop excision of the transformation zone (LLETZ) were scheduled at an appropriate facility for the LLETZ procedure. HPV-positive FSWs without any visible lesion on VIA/VILI-DC were administered TA. Bivariate analyses were conducted to compare demographic and clinical characteristics. Crude and adjusted logistic regression models were computed for HPV infection status and treatment uptake as outcomes in separate models and their ORs and 95% confidence intervals (95% CI) were reported. Among the 599 FSWs aged 30 years and older that were screened for HPV and VIA/VILI-DC, 62.1% (95% CI: (0.58-0.66)) were positive for one or more HPV types. HPV type 51 had the highest prevalence (14%), followed by types 53 (12.4%) and 52 (12.2%). Type 18 had the lowest prevalence of 2.8% followed by type 16 with 5.2%. In the multivariable model, HIV-positive FSWs were 1.65 times more likely to be infected with HPV compared to their HIV-negative counterparts (AOR: 1.65, CI: 1.11-2.45). A total of 9.9% of the 599 FSWs were positive for VIA/VILI-DC. The prevalence of HPV infection among FSWs in Cameroon is higher than the worldwide pooled FSW prevalence. HPV types 51 and 53 were the most prevalent, while types 18 and 16 were the least prevalent. HIV status was the only variable that was significantly associated with infection with HPV.

The association between HIV infection and perimenopausal syndrome: A matched cross-sectional study of women living with HIV/ AIDS and their uninfected counterparts in rural areas of Anhui, China.

The study compared the level of perimenopausal syndrome (PS) among women age 40 or older living with HIV/AIDS (WLWH) and their HIV-negative counterparts in rural areas of Anhui, China and it analyzed the association between HIV infection and PS. From March 2018 to February 2019, WLWH ≥ the age of 40 and their aged-matched HIV-negative female neighbors in 8 townships in the cities of Fuyang and Bozhou in Anhui Province, China were selected by cluster random sampling to respond to a questionnaire survey. Multivariable logistic regression analysis was performed. Responses from a total of 464 participants were analyzed, including 220 HIV-positive women and 244 HIV-negative female neighbors. The average score for PS was 18.02 and the prevalence of PS was 85.0% in the HIV-positive group, both of which were higher than those in the control group (p < 0.05). The most common PS symptoms among WLWH were irritability (83.2%), followed by fatigue (79.5%) and arthralgia myalgia (68.2%). The risk of developing moderate to severe PS in HIV-uninfected women was 0.605 times that in WLWH. Other significant risk factors included being older, a history of chronic diseases, poor sleep quality, and poor appetite. In the future, more attention should be paid to the prevention of PS in WLWH while actively providing antiretroviral therapy and follow-up.

Pattern and Prevalence of Intestinal Helminthiasis among Human Immunodeficiency Virus-Infected Children at the University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu State.

Children infected with the human immunodeficiency virus (HIV) may be more prone to helminthic infestation because they have depleted immunity, which increases their susceptibility to infection and infestations, even with minimally pathogenic organisms such as helminths. The prevalence and pattern of intestinal helminthiasis among children living with HIV attending the University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla, Enugu. A cross-sectional study in which 70 HIV-infected children were consecutively recruited from the Pediatric HIV clinic and matched for age and sex with 70 children recruited from the children outpatient clinic (CHOP) of UNTH Ituku-Ozalla. Stool samples of study participants were collected and analyzed using the Kato-Katz method and subsequently examined under the microscope for helminths' eggs and larvae. The worm intensity was determined using the theoretical analytic sensitivity (TAS) of 24 eggs per gram (EPG) to obtain the number of eggs per gram of feces. The CD4+ count, which describes the severity of immunosuppression in HIV-positive children was determined using the PARTEC Cyflow counter for the CD4+ lymphocyte count, whereas HIV screening was performed using the rapid diagnostic tests for HIV (Determine, Statpack and Unigold). Data were analyzed using IBM SPSS. The prevalence of intestinal helminthiasis among HIV-infected and non-infected children was 27.1% and 12.9%, respectively (P = 0.038). HIV-positive children were more likely to have intestinal helminthiasis than HIV-negative children (odds ratio [OR] =2.525, 95% confidence interval [CI]: 1.052-6.063). Ascaris lumbricoides was the predominant helminthic species in both HIV-infected and non-infected groups; however, there was no statistical significance between intestinal helminthic species and HIV status (P = 0.655) but the severity of intestinal helminthiasis was significantly associated with decreasing CD4+ count (P = 0.028). The risk factors for intestinal helminthic infestation examined were similar in both HIV-positive and HIV-negative children (P > 0.05). There was a significantly higher prevalence of helminthic infestation among HIV-infected children compared to their HIV-negative counterparts. The severity of intestinal helminthiasis was significantly associated with decreasing CD4+ count.

Genomic Stability, DNA Repair and the SKP1-CUL1-F-Box Complex in HIV Associated Diffuse Large B-Cell Lymphoma

Introduction: Previously we demonstrated that HIV associated diffuse large B-cell lymphomas (DLBCL) of Germinal Center B-cell subtype (GCB) are more proliferative, with enhanced genomic stability and increased expression of DNA repair genes, particularly Fanconi anemia (FA) and homologous recombination (HR) genes compared to their HIV negative counterparts (Maguire et al, 2019). It is unknown if this signature is unique to the GCB subtype or if it is also observed in Activated B-cell (ABC) and Unclassified (UNC) DLBCL. Herein we validate our HIV associated GCB DLBCL findings in a larger independent cohort and report for the first time the aberrational profile of molecularly profiled HIV associated ABC DLBCL compared to their HIV negative counterparts respectively. Methods: An independent cohort of 353 DLBCL FFPE cases was assembled, including 125 HIV-DLBCL samples. All samples underwent hematopathological review to confirm diagnosis and determine tumor content. Samples with &amp;lt;60% tumor content were macro-dissected before they were RNA/DNA extracted. Cell of origin (COO) profiles were assessed using the Lymph3Cx molecular assay which can distinguish primary mediastinal B-cell lymphoma (PMBL) like from GCB, ABC and UNC DLBCL (Mottok et al 2018). Copy number (CN) analyses were performed on samples with sufficient DNA (41 HIV neg, 32 HIV pos) using the OncoScan FFPE assay kit and the resulting data analyzed using Chromosome Analysis Suite (ChAS) v4.1 and the multisample viewer module of Reproductive Health Research Analysis Software (RHAS) v1.1. Additional digital gene expression profiling was performed using the Pan-Cancer panel (NanoString, Seattle, WA) customized to include 9 BCL2 family genes for a total of 739 genes and analyzed using the NanoString nSolver Advanced Analysis module. Results: GCB, ABC, UNC and PMBL-like proportions were 50%, 30%, 14% and 6% in HIV unassociated (HIV neg) and 50%, 23%, 25% and 2% in HIV pos tumors respectively, confirming both cohorts were GCB-enriched by molecular profiling. PMBL-like cases were excluded from further analyses. OncoScan CN analyses showed that HIV pos DLBCL were significantly less aberrant than HIV neg DLBCL (median CN per sample 0.56 vs 1.01, p&amp;lt;0.001). HIV pos GCB tumors were significantly less aberrant than both HIV neg GCB tumors (median CN per sample 0.50 vs 1.11, p&amp;lt;0.001), and HIV pos ABC tumors (median CN per sample 0.50 vs 0.81, p=0.009). HIV pos ABC tumors were also less aberrant than HIV neg ABC tumors, however, the difference was not significant overall (median CN per sample 0.81 vs 1.03, p=0.162) or for gain/amplifications (median CN per sample 0.38 vs 0.42, p=0.814), but was borderline significant for loss/deletions (median CN per sample 0.31 vs 0.47, p=0.06). GEP analyses identified Cell Cycle and DNA repair as the top two upregulated pathways in HIV pos GCB tumors compared to HIV neg GCB tumors. In contrast, Cell Cycle and DNA repair were downregulated in HIV pos ABC tumors compared to HIV neg ABC tumors. However, one gene ( RBX1) was identified as significantly upregulated in both pathways in HIV pos GCB (adjusted p-value 0.0215) and HIV pos ABC (adjusted p-value 0.0046) tumors compared to their HIV neg counterparts. A second gene ( SKP1) was also significantly upregulated in HIV pos GCB (adjusted p-value 3.94E-5) and HIV pos ABC (adjusted p-value 0.0031) tumors. Together RBX1 and SKP1 encode the two principal functional subunits of the SKP1, CUL1, F-box protein (SCF) complex which is part of the ubiquitin proteasome system (UPS) and has been reported as essential for maintaining genome and chromosome stability (Thompson et al 2021). Conclusions: These results demonstrate that HIV pos DLBCL tumors are less aberrant than their HIV neg counterparts irrespective of COO subtype. However, the degree of genomic stability differs by COO, with HIV pos GCB tumors being more genomically stable than HIV pos ABC tumors. Although both have enhanced expression of UPS related SCF genes ( RBX1, SKP1), only HIV pos GCB tumors have enhanced expression of key DNA repair genes as well including Fanconi Anemia ( BRCA2/FANCD1, FANCL) and mismatch repair ( MSH2, MSH6) genes (adjusted p-values of ≤ 0.0263). Given the reported role of SCF in genomic stability maintenance, the HIV pos COO CN differences could be due to the contributions of both DNA repair and SCF mechanisms in HIV pos GCB and mainly SCF mechanisms in HIV pos ABC tumors.

Enhanced Genomic Stability in Monomorphic Post-Transplant Lymphoproliferative Disorders Is Driven By Distinct Mechanisms Stratified By EBV Status

Introduction: We previously showed that HIV associated EBV negative (-) diffuse large B-cell lymphomas (DLBCL) of germinal center origins (GCB) have enhanced genomic stability and increased expression of DNA repair genes compared to their HIV negative counterparts (Maguire et al 2019). Given that immune deficiency can be induced virally or therapeutically, including the administration of immunosuppressive drugs post solid organ or hematopoietic stem cell transplant, we questioned whether these observations are specific to HIV or if they represent a more global immune impaired signature. Here we assessed the genomic stability of monomorphic DLBCL post-transplant lymphoproliferative disorders (PTLD) and the potential role of DNA repair. Methods: A total of 49 monomorphic DLBCL PTLDs (26 EBV(-), 23 EBV positive (+)) and 170 immune competent (IC) DLBCL (EBV status unknown) were studied. All were pathologically reviewed and samples with &amp;lt;60% tumor content were macro-dissected before RNA/DNA extraction. Cell of origin (COO) profiles were assessed using the DLBCL90 molecular assay which can distinguish primary mediastinal B-cell lymphoma (PMBL) from GCB, Activated B-cell (ABC) and unclassified (UNC) DLBCL (Ennishi et al 2019). NanoString gene expression profiling (GEP) was performed using the PanCancer Pathways panel and analyzed using NanoString nSolver Advanced Analysis. Copy number (CN) analysis was performed on a subset of samples (45 PTLD, 41 DLBCL) using the OncoScan CN assay and analyzed using Chromosome Analysis Suite (ChAS) v4.1. All p-values listed were Benjamini-Hochberg adjusted and Mann-Whitney tested for the GEP and CN data respectively. Results: In contrast to IC-DLBCL which are GCB enriched (50%), COO profiling revealed PTLD to be ABC enriched (43%). CN analyses revealed that the median CN/sample for PTLD (0.57, p&amp;lt;0.001), EBV(+)PTLD (0.25, p&amp;lt;0.001) and EBV(-)PTLD (0.80, p = 0.050) tumors were significantly less aberrant than IC-DLBCL (1.01). The data also showed that EBV(+)PTLD are less aberrant than EBV(-)PTLD tumors (0.25 vs 0.80, p&amp;lt;0.001). GEP pathway analysis identified DNA repair as downregulated in PTLD and EBV(+)PTLD but upregulated in EBV(-)PTLD compared IC-DLBCL. Nine DNA repair genes ( RAD51, CCNA2a, CHEK1b, POLR2Da, PCNAa, WHSC1a, GTF2H3a, ATM c, EP300 c) were differentially expressed (DE) in EBV(-)PTLD compared to IC-DLBCL (7 increased, 2 decreased, p ≤ 0.0425): where the most overexpressed gene RAD51, a critical mediator of Homologous Recombination (HR) and the Fanconi Anemia (FA) DNA repair pathways, was not DE in PTLD or EBV(+)PTLD compared to IC-DLBCL. Five a genes were increased in PTLD (p ≤ 0.0204) but not EBV(+)PTLD, 1 b was decreased in EBV(+)PTLD (p = 0.01) but not PTLD and 2 c were reduced in PTLD regardless of EBV status compared to IC-DLBCL (p ≤ 0.0024). Twenty-8 genes were DE in EBV(+)PTLD compared to IC-DLBCL. Of these, 23 were downregulated (p ≤ 0.0418) and included HR, FA and mismatch repair genes ( CHEK1, CHEK2, BRAC1/FANCS, FANCA, FANCB, FANCE, MSH2, MSH6). All but 2/23 were similarly expressed in PTLD compared to IC-DLBCL of which 11 were significant (p ≤ 0.0356). The five upregulated genes ( ZBTB32, DDB2, NBN, POLB, RBX1, p ≤ 0.0092) were also upregulated in PTLD (p ≤ 0.0042) but not EBV(-)PTLD compared to IC-DLBCL. Two additional genes ( SKP1, FBXW7) were also identified as increased in EBV(+)PTLD and PTLD (p ≤ 0.0204) compared to IC-DLBCL. In contrast, SKP1 was increased (p = 2.7E-4) and FBXW7 was decreased (p = 0.3610) in EBV(-)PTLD compared to IC-DLBCL. Together the protein products of RBX1, SKP1 and FBXW7 comprise the functional cores of a complete UPS complex, the SCF FBXW7 E3 ubiquitin ligase which have been reported to regulate the DNA damage response and promote genomic stability. Conclusions: Like HIV associated DLBCL, these results show that PTLD is more genomically stable than IC-DLBCL, and that genomic stability is further enhanced in EBV(+)PTLD which have increased expression of UPS related genes. In contrast, EBV(-)PTLD have increased expression of DNA damage repair genes, including RAD51. In summary, monomorphic DLBCL PTLD tumors have enhanced genomic stability that appears to be mediated by two distinct mechanisms stratified by EBV status. Further work is required to assess if this stratification of mechanisms is unique to PTLD or reflects a more global immune impaired EBV related signature.

Painful to Discuss: The Intersection of Chronic Pain, Mental Health, and Analgesic Use among People with HIV

Objective: This retrospective chart review study aims to identify patients in an HIV clinical setting in an area of high HIV prevalence in Atlanta, Georgia, USA who have chronic pain, analgesic prescriptions, and/or mental health diagnoses. Design: People living with HIV (PLWH) are at higher risk for experiencing trauma, mental health conditions, and chronic pain than their HIV-negative counterparts. This study was designed to evaluate the intersection of these factors within an urban HIV clinic. Methods: Retrospective chart review study. Results: Of the adult patients enrolled at an HIV clinic in Atlanta, Georgia USA between 2011-2022 (n=15,970), 93.7% were prescribed analgesics, 40.5% had documented pain diagnoses, and 23.5% had documented mental health diagnoses. Additionally, 14.3% of all enrolled patients had all three factors concurrently. Conclusions: The complexity of HIV, chronic pain, mental health challenges, and analgesic use demand a patient-centered, collaborative approach including a multidisciplinary care team. Seeing persistent pain among PLWH with a trauma-informed approach to care within the lens of co-occurring mental health diagnoses will allow us to better understand, treat, and sustain patients in life-saving HIV care.

Disease awareness and healthcare utilization in rural South Africa: a comparative analysis of HIV and diabetes in the HAALSI cohort

BackgroundStudies from rural South Africa indicate that people living with HIV (PLHIV) may have better health outcomes than those without, potentially due to the frequent healthcare visits necessitated by infection. Here, we examined the association between HIV status and healthcare utilization, using diabetes as an illustrative comparator of another high-burden, healthcare-intensive disease.MethodsOur exposure of interest was awareness of positive disease status for both HIV and diabetes. We identified 742 individuals who were HIV-positive and aware of their status and 305 who had diabetes and were aware of their status. HIV-positive status was further grouped by viral suppression. For each disease, we estimated the association with (1) other comorbid, chronic conditions, (2) health facility visits, (3) household-level healthcare expenditure, and (4) per-visit healthcare expenditure. We used log-binomial regression models to estimate prevalence ratios for co-morbid chronic conditions. Linear regression models were used for all other outcomes.ResultsVirally suppressed PLHIV had decreased prevalence of chronic conditions, increased public clinic visits [β = 0.59, 95% CI: 0.5, 0.7], and reduced per-visit private clinic spending [β = -60, 95% CI: -83, -6] compared to those without HIV. No differences were observed in hospitalizations and per-visit spending at hospitals and public clinics between virally suppressed PLHIV and non-PLHIV. Conversely, diabetic individuals had increased prevalence of chronic conditions, increased visits across facility types, increased household-level expenditures (β = 88 R, 95% CI: 29, 154), per-visit hospital spending (β = 54 R, 95% CI: 7, 155), and per-visit public clinic spending (β = 31 R, 95% CI: 2, 74) compared to those without diabetes.ConclusionsOur results suggest that older adult PLHIV may visit public clinics more often than their HIV-negative counterparts but spend similarly on a per-visit basis. This provides preliminary evidence that the positive health outcomes observed among PLHIV in rural South Africa may be explained by different healthcare engagement patterns. Through our illustrative comparison between PLHIV and diabetics, we show that shifting disease burdens towards chronic and historically underfunded diseases, like diabetes, may be changing the landscape of health expenditure inequities.

Abstract 12157: Underutilization of Revascularization Procedures Among Patients Living With HIV Admitted to the US Hospitals With Acute Myocardial Infarction and Factors Associated With Higher Odds of Receiving Revascularization: A Cross-Sectional Study

Introduction: Despite significant improvements in the prevention and treatment of infection with the human immunodeficiency virus (HIV), people living with HIV (PLWH) suffer cardiovascular diseases to a more extent than HIV-negative patients. Research Question: Is there a disparity in the demographics and socioeconomic status of hospitalized PLWH with AMI, who undergo revascularization compared to those who do not? Methods: Data pertinent to admission cases with AMI was analyzed from the National Inpatient Sample registry between 2016 and 2019 to determine differences in the frequency and outcomes of revascularization (percutaneous or surgical) between PLWH and HIV-negative counterparts and identify factors associated with higher odds of undergoing revascularization. Results: The frequency of revascularization was significantly lower among PLWH with AMI than HIV-negative patients. The difference was more substantial for PCI than for CABG (Fig.1). Younger age, male gender, White race, residential of a zip code with higher income quartile or smaller metropolitan regions, private insurance or self-paid status, and hospitalization in the Western states were all associated with a higher likelihood of undergoing revascularization (Table1). Although total hospital charges were significantly higher for PLWH and AMI who underwent revascularization compared to those who did not, the length of hospital stay was significantly shorter. Conclusions: There is a significant disparity in revascularization approaches between HIV-positive and HIV-negative patients hospitalized with acute myocardial infarction.

HIV and Early Treatment Outcomes Among Women With Cervical Cancer Treated With Concurrent Chemoradiation in Tanzania.

Cervical cancer (CC) is the leading malignancy in Tanzania. Low-income countries are faced with double epidemics of HIV and CC. This study aimed to investigate how HIV and cancer stage at diagnosis affect early treatment outcomes among women with CC treated with concurrent chemoradiation in Tanzania in the highly active antiretroviral therapy era. This was a prospective cohort study of patients newly diagnosed with CC at the Ocean Road Cancer Institute from November 2019 to January 2020. The tumor response was assessed using RECIST 3 months post-treatment. The tumor response was categorized as a complete or partial response according to the ultrasound and pelvic examination findings. The univariate and multivariate logistic regression explained the relationship between several covariates (age, stage, HIV status, equivalent dose in 2 Gy fractions, chemotherapy cycles, and treatment time) and treatment response. A total of 102 patients with CC were included in this study at baseline. After adjusting for other covariates, only completion of treatment within 56 days (odds ratio [OR], 9.23; 95% CI, 1.53 to 55.85; P = .016) and receiving at least three cycles of cisplatin (OR, 5.6; 95% CI, 1.47 to 21.34; P = .012) were significantly associated with complete tumor response. HIV status was not significantly associated with complete tumor response (OR, 1.534; 95% CI, 0.424 to 5.545; P = .5144). Early treatment response was independent of HIV status. With wide coverage of anitretroviral therapy, patients with HIV can receive radical treatment and have the same early outcomes as their HIV-negative counterparts.

Rural-urban disparities in nutritional status among women in Ethiopia based on HIV serostatus: a cross-sectional study using demographic and health survey data

BackgroundEthiopia is one of the sub-Saharan African countries most affected by the human immunodeficiency virus (HIV) epidemic and also by severe undernutrition, which is particularly prevalent among women. HIV infection, reproductive biology, and their role in society increase the vulnerability of women to malnutrition. Various factors including urbanization could cause differences in the nutritional status of rural and urban residents. In this study, we aimed to assess rural-urban disparities in nutritional status among women of reproductive age based on HIV serostatus in Ethiopia.MethodData from the Ethiopian Demographic and Health Survey (EDHS) conducted in 2016 were used. Among 15,683 women included in the survey, 8822 non-pregnant women aged 15–49 years, including those who gave birth two months before the DHS survey were included in this study. Multinomial logistic regression was used to determine the relative risk ratios (RRR) for the associations between study variables.ResultsGenerally, the prevalence of underweight among women of reproductive age was higher in rural residents (28.9%) than in urban residents (12.3%) in Ethiopia. Being overweight was more prevalent among urban women than rural women, (35.1% vs. 4.8%). About 32% of HIV-positive women were underweight in both rural and urban areas. About 29% of HIV-positive urban women were overweight compared to 3.4% of HIV-positive rural women. Among urban residents, HIV-positive women were about 4 times more likely to be underweight than their HIV-negative counterparts, RRR 3.8 (95% CI: 1.58, 9.26). However, there was no significant difference in nutritional status between HIV-positive and HIV-negative women living in rural areas. Anemic women were more likely to be underweight while, wealthy women were less likely to be underweight in both rural and urban areas. Women aged 25–49 years were generally more likely to be overweight/obese and less likely to be underweight compared to younger women aged le 24years.ConclusionMalnutrition was more prevalent among HIV-positive women living in urban Ethiopia. Targeted nutritional interventions for HIV-positive women of reproductive age living in urban areas could be considered. Furthermore, efforts should be made to improve the nutritional status of women of reproductive age across the country.