Mental Health, ART Adherence, and Viral Suppression Among Adolescents and Adults Living with HIV in South Africa: A Cohort Study.

We followed adolescents and adults living with HIV aged older than 15 years who enrolled in a South African private-sector HIV programme to examine adherence and viral non-suppression (viral load > 400 copies/mL) of participants with (20,743, 38%) and without (33,635, 62%) mental health diagnoses. Mental health diagnoses were associated with unfavourable adherence patterns. The risk of viral non-suppression was higher among patients with organic mental disorders [adjusted risk ratio (aRR) 1.55, 95% confidence interval (CI) 1.22-1.96], substance use disorders (aRR 1.53, 95% CI 1.19-1.97), serious mental disorders (aRR 1.30, 95% CI 1.09-1.54), and depression (aRR 1.19, 95% CI 1.10-1.28) when compared with patients without mental health diagnoses. The risk of viral non-suppression was also higher among males, adolescents (15-19 years), and young adults (20-24 years). Our study highlights the need for psychosocial interventions to improve HIV treatment outcomes-particularly of adolescents and young adults-and supports strengthening mental health services in HIV treatment programmes.

RESUMEN: Monitoreamos adolescentes y adultos mayores de 15 años que viven con VIH y que están registrados en un programa privado Surafricano para el tratamiento del VIH. Nuestro propósito fue examinar adherencia a los medicamentos y supresión viral (carga viral < 400 copias/mL) en los participantes con (20,743, 38%) y sin (33,635, 62%) diagnósticos de salud mental. Los diagnósticos de salud mental estuvieron asociados con patrones de adherencia desfavorables. Comparados con pacientes sin diagnósticos de salud mental, el riesgo de no supresión viral fue más alto entre pacientes con desórdenes mentales orgánicos [riesgo relativo ajustado (aRR) 1.55, 95% intervalo de confidencia (CI) 1.22­1.96], desórdenes en el uso de sustancias (aRR 1.53, 95% CI 1.19­1.97), desórdenes mentales serios (aRR 1.30, 95% CI 1.09­1.54), y depresión (aRR 1.19, 95% CI 1.10­1.28). El riesgo de no supresión viral también fue más alto en hombres que en mujeres, en adolescentes (15­19 años), y en adultos jóvenes. Nuestro estudio resalta la necesidad de intervenciones psicosociales para mejorar los resultados del tratamiento contra el VIH ­particularmente en adolescentes y adultos jóvenes­, y respalda el fortalecimiento de servicios de salud mental como parte de los programas para el tratamiento del VIH.

Immune Checkpoints, Inhibitors and Radionuclides in Prostate Cancer: Promising Combinatorial Therapy Approach.

Emerging research demonstrates that co-inhibitory immune checkpoints (ICs) remain the most promising immunotherapy targets in various malignancies. Nonetheless, ICIs have offered insignificant clinical benefits in the treatment of advanced prostate cancer (PCa) especially when they are used as monotherapies. Current existing PCa treatment initially offers an improved clinical outcome and overall survival (OS), however, after a while the treatment becomes resistant leading to aggressive and uncontrolled disease associated with increased mortality and morbidity. Concurrent combination of the ICIs with radionuclides therapy that has rapidly emerged as safe and effective targeted approach for treating PCa patients may shift the paradigm of PCa treatment. Here, we provide an overview of the contextual contribution of old and new emerging inhibitory ICs in PCa, preclinical and clinical studies supporting the use of these ICs in treating PCa patients. Furthermore, we will also describe the potential of using a combinatory approach of ICIs and radionuclides therapy in treating PCa patients to enhance efficacy, durable cancer control and OS. The inhibitory ICs considered in this review are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD1), V-domain immunoglobulin suppressor of T cell activation (VISTA), indoleamine 2,3-dioxygenase (IDO), T cell Immunoglobulin Domain and Mucin Domain 3 (TIM-3), lymphocyte-activation gene 3 (LAG-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), B7 homolog 3 (B7-H3) and B7-H4.

Cancer treatment and survival among cervical cancer patients living with or without HIV in South Africa.

Objective: To compare cancer treatment and all-cause mortality between HIV-positive and HIV-negative cervical cancer patients in South Africa. Methods: We assessed cancer treatment and all-cause mortality in HIV-positive and HIV-negative cervical cancer patients who received cancer treatment within 180 days of diagnosis using reimbursement claims data from a private medical insurance scheme in South Africa between 01/2011 and 07/2020. We assessed treatment provision using logistic regression and factors associated with all-cause mortality using Cox regression. We assigned missing values for histology and ethnicity using multiple imputation. Results: Of 483 included women, 136 (28 %) were HIV-positive at cancer diagnosis (median age: 45.7 years), and 347 (72 %) were HIV-negative (median age: 54.1 years). Among 285 patients with available ICD-O-3 morphology claims codes, the proportion with cervical adenocarcinoma was substantially lower in HIV-positive (4 %) than in HIV-negative patients (26 %). Most HIV-positive patients (67 %) were on antiretroviral therapy at cancer diagnosis. HIV-positive patients were more likely to receive radiotherapy (adjusted odds ratio [aOR] 1.90, 95 % confidence interval [CI] 1.05-3.45) or chemotherapy (aOR 2.02, 95 %CI 0.92-4.43) and less likely to undergo surgery (aOR 0.53, 95 %CI 0.31-0.90) than HIV-negative patients. HIV-positive patients were at a higher risk of death from all causes than HIV-negative patients (adjusted hazard ratio 1.52, 95 %CI 1.06-2.19). Other factors associated with higher all-cause mortality included age > 60 years and metastases at diagnosis. Conclusions: HIV-positive cervical cancer patients in South Africa had higher all-cause mortality than HIV-negative patients which could be explained by differences in tumour progression, clinical care, and HIV-specific mortality.

Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma.

Glioblastoma (GB) remains the most fatal brain tumor characterized by a high infiltration rate and treatment resistance. Overexpression and/or mutation of receptor tyrosine kinases is common in GB, which subsequently leads to the activation of many downstream pathways that have a critical impact on tumor progression and therapy resistance. Therefore, receptor tyrosine kinase inhibitors (RTKIs) have been investigated to improve the dismal prognosis of GB in an effort to evolve into a personalized targeted therapy strategy with a better treatment outcome. Numerous RTKIs have been approved in the clinic and several radiopharmaceuticals are part of (pre)clinical trials as a non-invasive method to identify patients who could benefit from RTKI. The latter opens up the scope for theranostic applications. In this review, the present status of RTKIs for the treatment, nuclear imaging and targeted radionuclide therapy of GB is presented. The focus will be on seven tyrosine kinase receptors, based on their central role in GB: EGFR, VEGFR, MET, PDGFR, FGFR, Eph receptor and IGF1R. Finally, by way of analyzing structural and physiological characteristics of the TKIs with promising clinical trial results, four small molecule RTKIs were selected based on their potential to become new therapeutic GB radiopharmaceuticals.

The Association of Tumor Burden by 18F-FDG PET/CT and Survival in Vulvar Carcinoma.

PURPOSE: The aim of this study was to assess the impact of 18F-FDG PET/CT metabolic parameters obtained at initial staging of vulva carcinoma on survival in women with and without HIV infection. PATIENTS AND METHODS: 18F-FDG PET/CT images of women with vulva cancer who are planned for definitive therapy were analyzed. SUVmax, SUVmean, MTV, and total lesion glycolysis (TLG) as well as whole-body MTV and whole-body TLG were computed. RESULTS: Twenty-five women were included with a mean age of 43.44 ± 10.32. The majority of the patients were HIV infected with a median CD4 count of 444.00 cells/mm3. The HIV-infected women are younger at diagnosis than their HIV-uninfected counterparts. All patients presented with inguinofemoral lymph node involvement, whereas half the patients had pelvic nodal metastasis. All the patients with distant visceral or skeletal metastasis were HIV infected. The lungs were the most common site of distant metastasis. When comparing the SUVmax, SUVmean, MTV, TLG, wbMTV, and wbTLG between HIV-infected and HIV-uninfected patients, we did not find statistical differences. Twelve patients (48%) were upstaged to metastatic disease. Seven patients had died at the time of analysis. The wbMTV and wbTLG were significantly higher in nonsurvivors than survivors. CONCLUSIONS: 18F-FDG PET/CT improves initial staging of squamous cell carcinoma among women with and without HIV infection. The whole-body tumor burden assessed by 18F-FDG PET metabolic metrics did not differ between HIV-infected and HIV-uninfected women. A higher whole-burden tumor burden is associated with a higher risk of mortality among women with vulva cancer.

18F-FDG PET/CT imaging of vulva cancer recurrence: A comparison of PET-derived metabolic parameters between women with and without HIV infection.

OBJECTIVE: To assess the patterns of recurrence of vulva cancer on 18F-FDG PET/CT and to compare the 18F-FDG PET metabolic metrics in patients with and without Human Immunodeficiency Virus (HIV). METHODS: Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumour volume (MTV and total lesion glycolysis (TLG) were obtained on Flourine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) images of women referred with suspected or confirmed vulva cancer recurrence. We compared HIV-infected and HIV-uninfected patients regarding pattern disease recurrence, age at diagnosis, and the PET-derived metabolic indices. RESULTS: We analyzed 33 patients with a mean age 50.76 ± 15.78 including 21 HIV-infected women. The majority of patients (94 %) had squamous cell carcinoma and 84.85 % were Blacks. Of the HIV-infected individuals, the median CD4 count was 526.0 cells/mm3 (IQR: 379.0-729.0). HIV infected patients were younger than the HIV uninfected at the time of diagnosis: 40.50 ±â€Š8.87 vs 66.54 ±â€Š9.71 respectively, p < 0.001. We found a local (vulvar) recurrence rate of 75.8 %. Nodal pelvic recurrences were higher in the HIV-infected patients than in the HIV uninfected patients (70 % vs 30 %, p = 0.027). Three patients had distant metastasis and all three were HIV-infected. There was a higher whole-body MTV and TLG among HIV-infected women compared with HIV-uninfected women, 103.39 vs 17.58 and 852.64 vs 101.79, respectively (p < 0.05 for both). CONCLUSION: HIV-infected women are diagnosed with vulva cancer at a younger age. HIV-infected patients had a higher rate of pelvic lymph node recurrence. There is a higher tumor burden at vulva cancer recurrence among women with HIV infection.

Comparison of Fluorine(18)-fluorodeoxyglucose and Gallium(68)-citrate PET/CT in patients with tuberculosis.

18F-FDG and 68Ga-citrate PET/CT have both been shown to be useful in the management of tuberculosis (TB). We compared the abnormal PET findings of 18F-FDG- and 68Ga-citrate-PET/CT in patients with TB. METHODS: Patients with TB on anti-TB therapy were included. Patients had a set of PET scans consisting of both 18F-FDG and 68Ga-citrate. Abnormal lesions were identified, and the two sets of scans were compared. The scan findings were correlated to the clinical data as provided by the attending physician. RESULTS: 46 PET/CT scans were performed in 18 patients, 11 (61 %) were female, and the mean age was 35.7 ± 13.5 years. Five patients also had both studies for follow-up reasons during the use of anti-TB therapy. Thirteen patients were co-infected with HIV. 18F-FDG detected more lesions than 68Ga-citrate (261 vs. 166, p < 0.0001). 68Ga-citrate showed a better definition of intracerebral lesions due to the absence of tracer uptake in the brain. The mean SUVmax was higher for 18F-FDG compared to 68Ga-citrate (5.73 vs. 3.01, p < 0.0001). We found a significant correlation between the SUVmax of lesions that were determined by both tracers (r = 0.4968, p < 0.0001). CONCLUSION: Preliminary data shows 18F-FDG-PET detects more abnormal lesions in TB compared to 68Ga-citrate. However, 68Ga-citrate has better lesion definition in the brain and is therefore especially useful when intracranial TB is suspected.