AIDS Research and Human Retroviruses

In persons living with HIV (PWH), non-AIDS-related tumors, including colorectal cancer (CRC), have become major health concerns worldwide since the introduction of highly active antiretroviral therapy. To date, no study has addressed the underlying molecular mechanisms in PWH with CRC. To explore the impact of PWH with CRC, we sequenced total RNA and DNA from individuals with HIV-negative and PWH formalin-fixed paraffin-embedded (FFPE) CRC for transcriptome and genome analyses. We performed RNA and DNA extraction from FFPE samples, library preparation, total RNA sequencing, and whole-genome sequencing. A total of 1,705 genes were found to be differentially expressed genes (DEGs), including 1,121 upregulated DEGs and 584 downregulated DEGs, in PWH compared with HIV-negative CRC. Functional pathway analysis revealed that the DEGs were enriched mainly in infectious and immune diseases and various metabolic processes. The immune infiltration results revealed that the numbers of activated dendritic cells (aDCs), natural killer T cells (NKT cells), and T follicular helper cells (Tfh cells) were greater and that the number of memory B cells was lower in patients with CRC than in PWH. Twelve hub genes involved in interferon-stimulated genes (ISGs)—IFI44, MX1, OAS1, OAS3, BST2, IFIT1, FGF2, EGF, CCL3, CCL4, SHH, and PPARG—are positively related to aDC, NKT, Tfh, and memory B cells. We found highly analogous insertions, deletions, and functional annotations of the detected single nucleotide polymorphisms and indel mutations in PWH and patients with HIV-negative CRC. This study provides new insights into crucial ISGs, immune infiltration, immune variants, and pathways involved in CRC with HIV infection.

This study aimed to identify key predictors of immunological failure in elderly patients with HIV receiving antiretroviral therapy (ART) through machine learning approaches. We conducted a retrospective analysis of 490 elderly patients with HIV (including 120 with immunological failure) treated at Guigang People’s Hospital from January 2009 to May 2024, using data extracted from the AIDS Comprehensive Prevention and Control Information System. Employing a two-stage analytical approach, we first applied least absolute shrinkage and selection operator (LASSO) regression to screen 50 potential risk factors, identifying 6 significant predictors. These were subsequently analyzed via logistic regression, revealing six protective factors: moderate disease stage [odds ratio (OR) = 0.401], AIDS stage (OR = 0.130), cotrimoxazole use (OR = 0.495), β2-microglobulin levels (OR = 0.755), platelet count (OR = 0.767), and alanine aminotransferase levels (OR = 0.760). Age was identified as an independent risk factor (OR = 1.275). Finally, the Shapley Additive explanations (SHAP) algorithm was utilized to rank feature importance, providing interpretable insights into predictor contributions. This study used machine learning (LASSO and logistic regression) to pinpoint critical predictors of immunological failure in elderly patients with HIV on ART, aiding early detection of high-risk individuals and informing prevention strategies.

When local epidemiology of endemic fungal infections is poorly understood, it is difficult to determine the clinical impact of screening for these pathogens in people living with HIV. We found no Histoplasma urine antigen or serum antibody in over 450 symptomatic patients with a new diagnosis of HIV in Port-au-Prince, Haiti. These findings indicate that systematic testing is likely to be low yield in Port-au-Prince, although it is well described in other countries in the region, and may have higher prevalence in rural areas. These findings are relevant to other settings where the prevalence of histoplasmosis is poorly defined, as similar studies could also inform local evidence-based guidelines.

Liver fibrosis presents a unique diagnostic challenge in people coinfected with hepatitis C virus (HCV) and human immune deficiency virus (HIV). This study aimed to explore the association between CD4 discordance and liver fibrosis in that population, alongside assessing the predictive power of different models for significant fibrosis. A cross-sectional study was conducted on 198 adult people with HIV/HCV coinfection. Liver fibrosis was noninvasively assessed using transient elastography, and CD4 discordance was defined based on the discrepancy between absolute CD4 cell count and CD4 cell percentage. Multivariate logistic regression and receiver operating characteristic curves were used for analysis. Only 52 (26.3%) individuals had concordant CD4 values. The study found a significant correlation between high CD4 discordance and significant liver fibrosis (p < .001), with a higher prevalence of significant fibrosis in those with high discordance (65.5%) than those with low (14.5%) or concordant (13.5%) CD4 values. High CD4 discordance was strongly associated with significant fibrosis (odds ratio = 11.48, p < .001). The CD4-only model showed a high negative predictive value (87.5%), making it suitable for excluding significant fibrosis. In contrast, models incorporating both CD4 count and percentage demonstrated higher positive and negative predictive values (78.6% and 87.6%, respectively), indicating their utility in diagnosing significant fibrosis. This study highlights the complexity of assessing liver fibrosis in HIV/HCV-coinfected individuals and underscores the value of CD4 discordance as a predictive factor. The predictive models, especially those combining CD4 count and percentage, provide an approach for evaluating liver fibrosis. Further research is needed to refine these models and enhance their clinical applicability.

The human T-lymphotropic virus 1 (HTLV-1) affects millions globally, notably in Brazil. The classical neurological presentation of this infection is HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is limited information on its association with lipid disorders and cardiovascular risks. Here, we compare the lipid profile of 30 people with HTLV-1 and HAM/TSP to 73 people with HTLV-1 without evidence of HAM/TSP from a Brazilian reference center between July 2021 and September 2023. People with HAM/TSP had lower levels of high-density lipoprotein and higher levels of low-density lipoprotein (LDL) and total cholesterol than people without HAM/TSP. In addition, people with HAM/TSP had a sixfold risk increase for elevated LDL. Therefore, patients with HAM/TSP show an adverse lipid profile, indicating higher dyslipidemia and cardiovascular risks. Regular lipid monitoring in this group is recommended.