Current HIV Research - Online First

Since the introduction of antiretroviral therapy (ART), non-AIDS malignancies—particularly anal cancer—have increased in people living with HIV (PLHIV). However, associated risk factors and disease progression remain poorly defined.

This retrospective observational study analysed PLHIV who developed anal cancer between 2000 and 2021 at a third-level university hospital. Epidemiological, immunological, and microbiological factors, as well as disease management and outcomes, were assessed.

A total of 38 patients were included, 95% of whom were men, with an incidence rate of 105 cases per 100,000 person-years. The median CD4 nadir was 169 cells/μl, with 60% of patients having a CD4 nadir <200 cells/μl, and 93.3% had a CD4/CD8 ratio <0.4. HPV infection was documented in 100% of tested patients (35/38), and 50% presented with advanced tumor stages. At 2 years post-diagnosis, 66% achieved complete remission, while 13.2% had a recurrence. Long-term tumor-related mortality was 15%, with an overall survival of 66%.

A significant number of patients presented with advanced-stage anal cancer and ongoing immunosuppression, emphasising the need for earlier detection and better follow-up. Despite guidelines, screening participation remains low, highlighting the importance of multidisciplinary care and targeted prevention strategies in high-risk PLHIV populations. However, as a retrospective single-centre study with a limited sample size, our findings may be affected by information and selection bias, restricting broader applicability.

Co-infection with HIV and HPV and low CD4 nadir were common features in these patients. HPV prevention and anal dysplasia screening are crucial to reducing this emerging condition.

The present study investigated the molecular mechanism by which the transactivator of transcription (Tat) protein of Human Immunodeficiency Virus 1 (HIV-1) activates the replication cycle of Kaposi’s Sarcoma-associated Herpesvirus (KSHV).

BCBL-1 cells were initially infected with lentivirus overexpressing HIV-1 Tat. The relative mRNA expression of Farnesyl Diphosphate Farnesyltransferase 1 (FDFT1), HIV-1 Tat, KSHV Open Reading Frame 73 (ORF73), and KSHV Open Reading Frame 50 (ORF50) was quantified by real-time fluorescent quantitative Polymerase Chain Reaction (RT-qPCR). The cellular cholesterol levels were determined using a total cholesterol assay kit. BCBL-1 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) served as a positive control for the lytic replication of KSHV. The relative mRNA expression levels of HIV-1 Tat, FDFT1, KSHV ORF73, and KSHV ORF50 were subsequently evaluated in BCBL-1 cells following infection with lentiviruses for FDFT1 overexpression or FDFT1-RNAi knockdown, and the cellular cholesterol content was quantified.

The findings revealed that HIV-1 Tat downregulated FDFT1 and upregulated the expression of KSHV ORF50 in BCBL-1 cells. FDFT1 overexpression upregulated the expression of the latency-associated gene, ORF73, of KSHV in BCBL-1 cells, while knockdown of FDFT1 upregulated the expression of genes associated with the lytic reactivation of KSHV. Infection with the HIV-1 lentivirus, which overexpresses Tat, as well as manipulation of FDFT1, significantly altered the cholesterol content in BCBL-1 cells.

The downregulation of FDFT1 by HIV-1 Tat modulates cellular cholesterol levels and is associated with KSHV replication in BCBL-1 cells.

Peripheral blood lymphocyte subsets have been shown to influence prognosis in HIV-associated Diffuse Large B-Cell Lymphoma (HIV-DLBCL), a rare and highly aggressive form of non-Hodgkin's lymphoma linked to immunosuppression and abnormal B-cell proliferation. To lay the foundation for individualized therapy based on factors such as CD4⁺/CD8⁺ ratio and Treg/NK cell characteristics, this retrospective study was conducted to explore the variations in lymphocyte subset levels.

Overall, 51 HIV-DLBCL patients, 50 DLBCL patients, and 42 Healthy Donors (HD) were enrolled in the study. Data were extracted from outpatient records and the Hospital Information Management System. SPSS 27.0 software was used for statistical analysis of the data.

Significant differences in lymphocyte subsets were observed between groups. HIV-DLBCL patients showed decreased CD4⁺ T cell and regulatory T cell (Treg) counts/percentages compared to DLBCL patients and HD, but increased CD8⁺ T cell counts and percentages, as well as Treg percentages. Age-stratified analysis revealed that older HIV-DLBCL patients had lower CD8⁺ T cell counts, reduced CD3⁺ T cell percentages, and elevated CD56⁺CD16⁺ NK cell proportions compared to their younger counterparts.

This study revealed a distinct pattern of immune dysregulation in HIV-DLBCL patients, characterized by CD4⁺ T cell depletion and CD8⁺ T cell expansion, which is consistent with previous studies. Age-related immunosenescence may exacerbate the increased proportion of NK cells and the decline in T-cell function, suggesting a poorer prognosis in elderly patients. However, the lack of association between lymphocyte subsets and chemotherapy efficacy may reflect the broad impact of standard regimens on immune reconstitution. Limitations include the small sample size, absence of functional experiments, and failure to assess the influence of co-infections. Future studies should expand the cohort and integrate multi-omics data to validate these findings.

Patients with HIV-DLBCL have distinctive alterations in peripheral blood lymphocyte subsets, such as a decreased absolute count and percentage of CD4⁺ T cells, in comparison to individuals with DLBCL. These alterations appear age-related and showed no significant association with prior antiretroviral therapy. The therapeutic effect of chemotherapy for HIV-DLBCL, however, might not be impacted by the low absolute count and percentage of CD4⁺ T-cells in peripheral blood, as well as whether or not they had previously received antiretroviral therapy.

Toxoplasma gondii (T. gondii) can cause serious complications in both immunocompetent and immunosuppressed individuals. This study aims to assess the seroprevalence of T. gondii among HIV-positive individuals and to investigate its association with age, sex, CD4⁺ T cell count, HIV RNA levels, and hematological parameters.

This study included 247 HIV-positive individuals followed up at a tertiary care hospital between November 1, 2022, and November 30, 2024. We analyzed serum samples for T. gondii IgG antibodies using electrochemiluminescent microparticle immunoassay.

The prevalence of T. gondii IgG seropositivity was found to be 32.8% (n=81; 95% CI: 26.9-39). The median age of seropositive individuals was 52 years (IQR: 42-61), which was significantly higher compared to seronegative individuals (p<0.001). The highest IgG seropositivity rate (66.7%) was observed in the 61-80 age group. Hemoglobin levels were significantly lower in IgG seropositive individuals (p=0.040). Logistic regression analysis indicated an increased risk of T. gondii infection with advancing age. The odds ratio for the 41-60 age group was 13.3 (95% CI: 1.6-106, p=0.02), while for the 61-80 age group, it was 28 (95% CI: 3.3-240, p=0.002).

The seroprevalence of T. gondii in HIV-positive individuals was lower than both global and regional averages. Age was identified as an independent risk factor for T. gondii seropositivity. Additionally, hematological alterations associated with anemia were observed in seropositive individuals. Further large-scale, multi-center, and regionally representative studies are required to optimize T. gondii infection management and screening strategies in people living with HIV.

These findings suggest that T. gondii infection in HIV-positive individuals increases with age and may be associated with anemia, highlighting the need for age-focused screening and management strategies.

The effectiveness of antiretroviral therapy (ART) in treating HIV is influenced by the clinical response of patients, which, in turn, impacts the development of drug resistance. This study aimed to assess the correlation between clinical treatment response and resistance to first-line reverse transcriptase inhibitors in HIV patients receiving treatment for ≤12 and >12 months in South Sulawesi, a province in Indonesia.

In this cross-sectional study, 36 people living with HIV (PLHIV) experiencing virological failure (VF) were sampled from HIV services in the province from August 2022 to January 2023. HIV-1 viral RNAs were extracted, sequenced, and analyzed for drug sensitivity and resistance classification using the Stanford University HIV Drug Resistance Database (HIVdb) according to World Health Organization (WHO) recommendations, determining resistance levels and HIV subtypes. Phylogenetic analysis of PR-RT sequences (~1200 base pairs) was performed using the Muscle program and MEGA11 software, utilizing the neighbor-joining method with the Kimura two-parameter model.

Genotyping of plasma samples revealed that a significant proportion of patients exhibited mutations associated with resistance to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) (48.6% and 51.4%, respectively). Clinical response indicators, such as initial body mass index and occurrence of opportunistic infections, were found to correlate with specific drug resistance, highlighting the importance of monitoring treatment response. Moreover, virologic response showed strong associations with resistance to specific drugs, suggesting the need for tailored therapeutic approaches. Patient behaviors related to transmission risk factors were also found to be linked to resistance levels, underscoring the multifactorial nature of resistance development.

Overall, this study underscores the importance of considering treatment response in managing HIV and suggests implications for optimizing therapy regimens to mitigate resistance emergence.