Search Results (124)

HIV/AIDS continues to pose a significant global public health concern, with Sub-Saharan Africa having the highest number of people living with HIV (PLHIV). Traditional medicines have been increasingly essential in treating and managing PLHIV. Product Nkabinde (PN), a polyherbal formulation derived from traditional medicinal plants, has recently demonstrated significant potential in the treatment of HIV. This study aims to elucidate the molecular mechanisms underlying the therapeutic effects of phytochemicals identified from PN in HIV treatment, utilizing network pharmacology and molecular docking. The intersecting (common) genes of the 27 phytochemicals of PN and HIV were computed on a Venn diagram, while the protein–protein interaction (PPI) network of the intersecting genes was plotted using STRING. The hub (10) genes were computed and analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathways using ShinyGO. Molecular docking and protein–ligand interaction analysis of the 27 phytochemicals with each of the 10 hub genes were performed using the Maestro Schrodinger suite. The KEGG analysis reveals an important network with lower False Discovery Rate (FDR) values and higher fold enrichment. The pathway enrichments reveal that the 10 hub genes regulated by PN focus on immune regulation, metabolic modulation, viral comorbidity, carcinogenesis, and inflammation. GO analysis further reveals that PN plays key roles in transcription regulation, such as miRNA, responses to hormones and endogenous stimuli, oxidative stress regulation, and apoptotic signalling, kinase binding, protein kinase binding, transcription factor binding, and ubiquitin ligase binding enriched pathways. Consequently, molecular docking unveils complexes with higher binding energies, such as rutin-HSP90AA1 (−10.578), catechin-JUN (−9.512), quercetin-3-O-arabinoside-AKT1 (−9.874), rutin-EGFR (−8.127), aloin-ESR1 (−8.585), and quercetin-3-0-β-D-(6′-galloyl)-glucopyranoside-BCL2 (−7.021 kcal/mol). Overall, the results reveal pathways associated with HIV pathology and possible anti-HIV mechanisms of PN. Therefore, further in silico, in vitro, and in vivo validations are required to substantiate these findings. Full article

Background/Objectives: Having access to antiretroviral therapy (ART) has altered the health status of people living with HIV (PLHIV) to that of having a chronic condition, with a greater life expectancy. The development of the Veterans Aging Cohort Study (VACS) Index has allowed for the prediction of 5-year mortality in PLHIV, using both HIV-related and non-HIV-related markers. The modified Charlson Index describes the comorbidity burden and is indicated to predict 10-year mortality. This study validates the Veterans Aging Cohort Study (VACS) Index 1.0 and the modified Charlson Index in a contemporary European cohort, with the aim of better predicting mortality. Methods: An observational, multicenter study was conducted using data from the eVIHa cohort in the Balearic Islands (Spain) from 2000 to 2023. The VACS Index 1.0 and the modified Charlson Index were calculated. Model discrimination was assessed using Harrell’s C-statistic, and observed mortality was estimated using Kaplan–Meier analysis. Results: Of 6913 eligible PLHIV, 4480 (64.8%) had sufficient data for VACS Index calculation and were included in the primary analysis. The excluded group (N = 2433) had significantly higher mortality (27.7% vs. 9.4%) and a greater proportion of people who inject drugs. In the analyzed cohort, the VACS Index 1.0 showed good discrimination for 5-year all-cause mortality (C-statistic: 0.759), outperforming the modified Charlson Index (C-statistic: 0.729). Discrimination was the highest for deaths from liver disease (C: 0.875) and non-HIV-related infections (C: 0.853). Conclusions: In our analyzed cohort, the VACS Index 1.0 accurately predicted 5-year mortality. However, its performance in populations with higher rates of people who inject drugs and irregular follow-up is unknown and likely to be lower. Clinicians should be aware of these limitations when applying the index in practice. Full article

Background: The Coronavirus Disease 2019 (COVID-19) remains a major global public health issue. People living with HIV (PLHIV) are among the vulnerable groups facing a higher risk of severe outcomes. Combining COVID-19 vaccination with HIV services can improve access and utilization of the vaccine among PLHIV although effective methods of delivery are yet to be ascertained. We conducted a scoping review to identify and describe models for delivering COVID-19 vaccines through HIV care services in low- and middle-income countries (LMICs). Methods: We used PRISMA-ScR guidelines to conduct the review. On 3rd and 4th February 2025, we searched PubMed, Web of Science, Cochrane Library, and EMBASE for studies on integrated COVID-19 vaccine delivery for PLHIV. Results: Three studies from sub-Saharan Africa reported call-back strategy, diverse partnership, and mixed service delivery models for implementing COVID-19 vaccination in HIV care services. Key strategies that were used included building capacity, generating demand, managing the supply chain, and involving stakeholders. The outcomes showed significant increases in vaccination coverage among PLHIV and reduced vaccine wastage. Conclusions: Integrating COVID-19 vaccination into HIV services is practical and effective in LMICs. It makes use of current infrastructure, partnerships, and local innovations. Full article

Mycobacterium tuberculosis (TB) antigen-based skin tests, known as TB-specific skin tests (TBSTs), have been recommended by the World Health Organization (WHO) to test for TB infection (TBI). In light of these new recommendations, we conducted a situational analysis and market assessment to evaluate the utility of testing for TBI in general and of the new TBSTs in South Africa. We found the following barriers to acceptability of testing for TBI overall, regardless of the test: the perceived high prevalence of TBI; prior experiences of poor TB preventive treatment (TPT) uptake, which has led to the removal of TBI tests from the current TPT guidelines; and a poor sensitivity of previous TBI tests in people living with HIV (PLHIV). In addition, further barriers to the new TBSTs in particular were as follows: patient level barriers linked to repeat visits; the need for cold chains; and the need for a strong laboratory system, which reduces the need for point-of-care options. TBI testing was thought to be potentially useful to determine the eligibility for TPT in these use cases: healthcare workers, pregnant women living with HIV and prisoners. One other use case was in the TB diagnoses of children, where it was thought that a positive immunological test (TST/IgRA/TBST) could indicate a TB contact and serve as a ‘rule in’ test to strengthen the evidence for TB disease as a cause. Full article

Purpose: The COVID-19 pandemic has led to the publication of numerous primary studies and meta-analyses; however, conclusive evidence on whether HIV infection influences COVID-19 outcomes among people living with HIV (PLHIV) is still lacking. This research uses a novel technique, the exit meta-analysis, to conclusively update the evidence of HIV’s impact on COVID-19-related mortality, hospitalization, and need for Intensive Care Unit (ICU) admission in severe disease. Methods: A search of PubMed, EMBASE, Cochrane Reviews (CDSR), SCOPUS, CINAHL reviews and Google Scholar databases was conducted up to the 18 January 2024 for meta-analyses and observational studies that reported adjusted associations for the effect of HIV on COVID-19 related mortality, hospitalization, and ICU admission. Evidence from existing meta-analyses was summarized narratively, and an updated meta-analysis was carried out using a bias-adjusted inverse variance heterogeneity model. Subgroup analysis was carried out for age groups and geographical regions. Results: Of 3153 records identified, 20 meta-analyses and 56 primary studies, with a total of 27,936,428 participants, including 655,882 PLHIV, were included. A review of the meta-analyses showed conflicting results for all outcomes. In the updated synthesis, HIV was associated with higher odds of mortality (aOR 1.43, 95% CI: 1.01–1.86, I² = 90.7%) and ICU admission (aOR 1.49, 95% CI: 0.67–2.30, I² = 88.8%), but not hospitalization (aOR 1.11, 95% CI: 0.78–1.48, I² = 97.5%). The results for both ICU admission and hospitalization include the null value, leading to lower certainty. The exit meta-analysis suggested conclusive results for mortality (DAts score = −0.012) and hospitalization (DAts score = −0.014), but not for ICU admission. Conclusions: This exit meta-analysis provides conclusive evidence that HIV increases mortality in people with COVID-19; however, more studies may be required to address ICU admission and hospitalization. Full article

Background: Most of the currently approved TB diagnostics are sputum-based. However, due to unusual clinical presentations of TB among HIV patients, they may not have TB symptoms and be able to produce sputum. Hence, these diagnostics may not be able to detect as many TB cases as possible among these patients. Therefore, this study assessed the performance of C-reactive protein (CRP) and interferon-gamma-inducible protein 10 (IP-10) as a screening tool for TB. Methods: This prospective study was conducted by consecutively recruiting patients with TB symptoms, collecting their sputum and blood samples, using sputum culture as the reference standard, and determining the best cut-off point of serum levels of CRP and IP-10 (separately and in combination) for TB diagnosis. Findings: CRP and IP-10 were measured in 408 patients with TB symptoms, of which 21% had culture-confirmed TB. CRP’s sensitivity and specificity were (91.4% and 33.2%), (95.3% and 42.6%) and (84.8% and 22.1%) for the whole study population, HIV-negative and HIV-positive patients, respectively. The sensitivity and specificity of IP-10 were (87.3% and 40.9%), (87.5% and 50.3%) and (79.4% and 47.2%) for the patients’ categories, respectively. Combination of CRP and IP-10 slightly improved the performance of the biomarkers among HIV-negative patients, with sensitivity of 97.5% and specificity of 43.3%. Interpretation: Though CRP and IP-10 performed better in HIV-negative patients than among people living with HIV (PLHIV), the performance of the biomarkers is lower than what is recommended by the WHO (sensitivity ≥ 90% and specificity ≥ 70%) for a TB screening tool. Hence, there is a need for better non-sputum-based TB diagnostics. Full article

Background: Tuberculosis (TB) is a leading cause of death among people living with HIV (PLHIV). While body mass index (BMI) affects TB risk, its association with latent tuberculosis infection (LTBI) in PLHIV is unclear. High-transmission settings, such as prisons, may further increase LTBI risk, yet this relationship has not been studied across both prison and community populations of PLHIV. Methods: We conducted a dual cross-sectional study of PLHIV in Jiangsu Province, China, recruiting participants from a prison hospital in 2021 and community healthcare facilities from July to November 2023. BMI was calculated from measured height and weight. LTBI was identified by a positive ESAT6-CFP10 (EC) skin test or the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay. Logistic regression and generalized additive models (GAMs) assessed the association between BMI and LTBI, adjusting for demographic, clinical, and behavioral confounders. Results: A total of 1799 PLHIV were included in the analysis, of whom 343 (19.07%) were recruited from prison settings and 1456 (80.93%) from community-based screening. The overall prevalence of LTBI was 13.79% (n = 248). Obesity (BMI ≥ 28 kg/m²) was linked to a significantly lower risk of LTBI (adjusted OR = 0.47, 95% CI: 0.23–0.95, p = 0.036), particularly when identified by EC testing (adjusted OR = 0.13, 95% CI: 0.03–0.54, p = 0.005). The BMI–LTBI association followed a nonlinear “U-shaped” pattern, with the lowest prevalence in individuals who were obese. Among those with CD4+ T cell counts < 500 cells/μL, the inverse association between obesity and LTBI was even more marked (adjusted OR = 0.20, 95% CI: 0.05–0.83, p = 0.027). Conclusion: In summary, obesity is significantly associated with a lower risk of LTBI among PLHIV, with an approximate 54% risk reduction. This inverse relationship was most pronounced when using the EC skin test. Full article

Tuberculosis preventive treatment (TPT) reduces the incidence of tuberculosis (TB) among people living with HIV (PLHIV), but its coverage remains suboptimal in most settings. We conducted a cross-sectional study to describe TPT uptake among PLHIV and factors influencing TPT initiation. Healthcare workers (HCWs) in selected facilities were trained and supported to strengthen TPT management among PLHIV, including children living with HIV (CLHIV). Of 1309 enrolled PLHIV, 1268 (97%) were eligible for TPT; 1078 (85%) initiated TPT, including 663/776 (86%) among those currently on ART and 415/492 (84%) among clients newly on ART. The major reasons for not starting TPT included stock-outs of TPT medicines, TB disease, and refusal of TPT, mostly by CLHIV and adults currently on ART. Optimal and sustained uptake of TPT can be achieved through ensuring uninterrupted stocks of TPT medicines, including shorter regimens and pediatric formulations, addressing knowledge deficits among HCWs, and improving demand for TPT by educating PLHIV and caregivers of CLHIV about the benefits and risks of TPT formulations. Full article

Social isolation is a critical but understudied concern for people living with HIV (PLHIV), particularly in rural U.S. communities where social visibility is high and access to supportive services is limited. Disclosure of HIV status is often framed as a health-promoting behavior that facilitates engagement with care and access to social support, yet it can also increase vulnerability to exclusion and isolation, especially where confidentiality is difficult to maintain. Using data from a pilot survey of rural PLHIV in the United States ($n=17$), this study examines when disclosure may function adaptively and when it may coincide with a heightened social burden. A Social Isolation Index was constructed from 15 indicators of exclusion across family, community, and institutional domains. Disclosure was measured both by the number of people informed and whether sexual partners were told. Typological methods and Qualitative Comparative Analysis (QCA) were applied to explore how disclosure patterns relate to race, sexual identity, and reported isolation. The results indicate that disclosure is not uniformly protective: several participants who disclosed widely also reported high levels of isolation, with heterosexual and Black participants often reporting a higher cumulative burden. These findings challenge one-size-fits-all assumptions about disclosure in public health messaging and underscore the need for tailored strategies that recognize both disclosure and nondisclosure as potentially adaptive responses in rural and marginalized communities. Full article

Despite advances in the understanding of Kaposi sarcoma (KS), research from resource-limited settings remains limited. This study aimed to estimate the proportion of epidemic visceral KS among Mexican people living with HIV (PLHIV) and to describe their clinical and biochemical characteristics. We included PLHIV with histopathologically confirmed KS who received care at the National Medical Center La Raza between March 2020 and February 2023. We calculated the prevalence of epidemic KS and epidemic visceral KS and analyzed clinical and biochemical variables potentially associated with visceral involvement. The prevalence of epidemic KS was 5.6%. Among these cases, 51.4% had visceral involvement, yielding an overall prevalence of 2.8%. Patients with epidemic visceral KS exhibited significantly higher rates of oral mucosal involvement and lower hemoglobin levels compared with those without visceral disease. These findings highlight the substantial burden of epidemic visceral KS in this population and should be confirmed in future studies with larger cohorts and robust designs aimed at identifying clinical and biochemical predictors of visceral involvement. Full article

Background: In people living with HIV (PLHIV), ongoing neuronal injury has shown a correlation with elevated levels of soluble markers of immune activation, such as sCD163. Additionally, various risk factors, such as injection drug use (IDU), can independently affect immune and cognitive functions, leading to neurocognitive impairment (NCI). However, the potential sCD163-IDU-NCI axis in ART-experienced PLHIV is not clear. This study aims to determine NCI prevalence and investigate the interplay between risk factors and sCD163 in Pakistani PLHIV. Methods: For this cross-sectional study, 150 PLHIV and 30 HIV-negative people who inject drugs (PWID) were recruited using a convenience sampling strategy. NCI screening was performed using the International HIV Dementia Scale (IHDS) tool. Blood samples from PLHIV were used to perform HIV recency testing using the Asante Rapid Recency Assay, and to evaluate sCD163 levels using ELISA. Sociodemographic and clinical data were collected from medical records. Subsequently, descriptive statistics were used to summarize data variables, while comparisons (two and multiple groups) between participants with and without NCI were conducted, respectively, using the Mann–Whitney test or Kruskal–Wallis test for continuous variables, and Fisher’s exact test for categorial variables. Receiver Operating Characteristic (ROC) curve analysis was performed to assess the discriminative ability of sCD163. Logistic regression was used to identify predictors of neurocognitive impairment. Results: The majority of PLHIV had IDU as a high-risk behavior. In PLHIV, the median age was 34.5 years (IQR: 30–41), ART duration was 35 months (IQR: 17–54), and median CD4 count was 326.5 cells/µL (IQR: 116–545.5). Long-term infections (>6 months post-seroconversion; median ART duration: 35 months; median CD4 counts: 326.5 cells/μL) were noted in 83.3% of PLHIV. IHDS-based screening showed that 83.33% (all PLHIV) and 50% (PLHIV with no IDU history) scored ≤ 9 on the IHDS, suggestive of NCI. IHDS-component analysis showed the memory recall to be significantly affected in PLHIV compared to controls (median score 3.2 versus 3.7, respectively, p < 0.001). Regression analysis showed only long-term infection (OR: 2.99, p = 0.03) to be significantly associated with neurocognitive impairment. sCD163 levels were significantly lower in PLHIV with NCI (mean = 7.48 ng/mL, SD = 7.05) compared to those without NCI (mean = 14.82 ng/mL, SD = 8.23; p < 0.0001), with an AUC of 0.803 (95% CI: 0.72–0.88). However, after adjusting for IDU history, the regression analysis showed an odds ratio for sCD163 of 0.998 (95% CI: 0.934, 1.067, p = 0.957), indicating no association between sCD163 levels and NCI. Conclusion: This study reports a high prevalence of NCI in Pakistani PLHIV, and no association between sCD163 and neurocognitive impairment in PLHIV after adjustment for a history of IDU. Long-term infection and IDU were significantly linked to NCI, while only IDU was associated with lower sCD163 levels, regardless of NCI. Full article

Background: Neurocysticercosis (NCC) and HIV co-infection frequently occur in sub-Saharan Africa, yet the accuracy of available serological tests for NCC in immunosuppressed patients is uncertain. Methodology: We performed a cross-sectional diagnostic study on 101 people living with HIV from two endemic districts in Tanzania. Participants provided serum for cysticercosis antigen ELISA and Western Blot IgG; any positive result prompted neuroimaging investigation with cerebral computed tomography. NCC was diagnosed according to the 2017 revised Del Brutto criteria based on cCT according to Del Brutto criteria modified to exclude serology. Sensitivity, specificity, and area under the receiver–operating–characteristic curve (AUC) were calculated and adjusted for CD4 count and HIV stage. Two algorithms were compared: parallel testing (“either-test-positive”) and sequential screening (Ag ELISA screen, western blot IgG confirm). Results: NCC prevalence was 23%. Western Blot IgG outperformed Ag ELISA (sensitivity 57% vs. 30%; specificity 87% vs. 86%; AUC 0.73 vs. 0.57). Western blot IgG sensitivity declined to 54% when CD4 < 500 cells µL⁻¹, while Ag ELISA remained low. Western blot IgG positivity independently predicted NCC (adjusted odds ratio 4.1, 95% CI 1.4–11.9); Ag ELISA did not. When we counted a positive if either test was positive (parallel rule), sensitivity rose to 78% and NPV to 87%. When we ran Ag ELISA only if IgG was negative (sequential rule), we saved 70% of IgG strips, kept specificity at 95%, and PPV at 69%, but sensitivity fell to 39%. Conclusions: Western blot IgG is the most reliable single serological test for NCC in PLHIV. Parallel testing increased sensitivity and NPV and may suit better primary-level facilities without routine imaging. Sequential testing achieved high specificity, PPV, and conserved test kits, making it ideal for centers with limited reagents or scanner access. Tiered use of these assays can streamline NCC diagnosis in T. solium endemic, resource-limited settings. Full article

Background/Objectives: Opportunistic fungal infections are common among people living with HIV (PLHIV) and contribute substantially to morbidity, mortality, and hospitalization rates in this population. This study aimed to determine the prevalence of dermatological manifestations of fungal infections in HIV-positive patients and examine their association with demographic, clinical, and immunological characteristics. Methods: A retrospective review of medical records from 2500 PLHIV treated at the Infectious Diseases Unit of “Andreas Syggros” Hospital for Skin and Venereal Diseases between 1988 and 2017. Data from patients diagnosed with opportunistic fungal infections were analyzed. Participants were classified as either antiretroviral therapy (ART)-naïve or already receiving treatment. Recorded fungal infections were correlated with epidemiological variables and CD4+ T-cell counts. Results: Opportunistic fungal infections were identified in 859 patients (34.36%), with a marked male predominance. Candidiasis was the most frequently reported condition, with a higher prevalence among female patients. Lower CD4+ counts were significantly associated with an increased risk of cryptococcal meningitis, esophageal candidiasis, Pneumocystis jirovecii pneumonia (PJP), and oral candidiasis, whereas higher CD4+ counts were more common in patients with dermatophytosis, onychomycosis, and pityriasis/tinea versicolor. Conclusions: Opportunistic fungal infections remain highly prevalent in PLHIV, particularly among those with advanced immunosuppression. CD4+ T-cell counts are key diagnostic and prognostic markers, reinforcing their importance in monitoring disease progression and guiding clinical management. Full article

Background: Despite virological suppression through antiretroviral therapy (ART), people living with HIV (PLHIV) may exhibit inadequate immune responses to vaccination, placing them at continued risk for preventable infectious diseases. Evidence regarding the durability of vaccine-induced immunity in PLHIV with vertically acquired infection remains limited. Methods: We conducted a cross-sectional observational study to evaluate humoral immunity to routine childhood vaccines in a cohort of PLHIV with perinatally acquired infection. Antibody titers against diphtheria, tetanus, measles, mumps, rubella, varicella, and hepatitis B (HBV) were retrospectively assessed via serological testing and review of medical records. Seroprotection rates were analyzed at predefined intervals following the completion of the primary immunization schedule. Multivariate analysis was used to explore potential predictors of long-term immune response. Results: A total of 85 individuals were included. Two years after completing the primary vaccination series, seroprotection rates were as follows: diphtheria 71%, tetanus 79%, measles 79%, mumps 67%, rubella 87%, and varicella 54%. Five years post-vaccination, 50–70% of participants maintained protective antibody levels, declining further to 50–58% after ten years. By twenty years, protective immunity dropped below 30% for all antigens except rubella (47%). HBV vaccine responses were notably poor, with only 60%, 37%, 24%, and 7.5% retaining protective anti-HBs titers at 2, 5, 10, and 20 years post-immunization, respectively. Time elapsed since vaccination was the sole significant predictor of seroprotection across all vaccines. Conclusions: In this cohort of vertically infected PLHIV, vaccine-induced immunity was suboptimal and declined markedly over time compared to the general population. These findings highlight the need for tailored immunization strategies, including timely boosters and regular serological monitoring, to maintain long-term protection in this high-risk group. Full article

Background/Objectives: Restored CD4 absolute counts (CD4AC) and CD4/CD8 ratio in the setting of continuous antiretroviral treatment (ART) do not exclude a low-level immune activation associated with HIV reservoirs, microbial translocation, or the side effects of ART itself, which accelerates the aging of people living with HIV (PLHIV). To delineate biomarkers of incomplete immune restoration in PLHIV on successful ART, we evaluated T-lymphocyte mitochondrial parameters in relation to phenotypic markers of immune exhaustion and senescence. Methods: PLHIV with sustained viral suppression, CD4AC > 500 and CD4/CD8 ratio >0.9 on ART (n = 39) were compared to age-matched ART-naïve donors (n = 27) and HIV(–) healthy controls (HC, n = 35). CD4 and CD8 differentiation and effector subsets (CCR7/CD45RA and CD27/CD28), activation, exhaustion, and senescence markers (CD38, CD39 Treg, CD57, TIGIT, and PD-1) were determined by flow cytometry. Mitochondrial mass (MM) and membrane potential (MMP) of CD8 and CD4 T cells were evaluated with MitoTracker Green and Red flow cytometry dyes. Results: ART+PLHIV differed from HC by increased CD4 TEMRA (5.3 (2.1–8.8) vs. 3.2 (1.6–4.4), p < 0.05), persistent TIGIT+CD57–CD27+CD28– CD8+ subset (53.9 (45.5–68.9) vs. 40.1 (26.7–58.5), p < 0.05), and expanding preapoptotic TIGIT–CD57+CD8+ effectors (9.2 (4.3–21.8) vs. 3.0 (1.5–7.3), p < 0.01) in correlation with increased CD8+ MMP (2527 (1675–4080) vs.1477 (1280–1691), p < 0.01). These aberrations were independent of age, time to ART, or ART duration, and were combined with increasing CD4 T cell MMP and MM. Conclusions: In spite of recovered CD4AC and CD4/CD8 ratio, the increased CD8+ MMP, combined with elevated markers of exhaustion and senescence in ART+PLHIV, signals a malfunction of the CD8 effector pool that may compromise viral reservoir latency. Full article