EBV-encoded microRNAs (miRNAs) have been identified and their functions are being studied. The expression pattern of these miRNAs in clinical samples of EBV-associated non–Hodgkin's lymphomas is unknown. We analyzed five primary “endemic” pediatric Burkitt's lymphomas (BL), two acquired immunodeficiency syndrome (AIDS)-related type I latency BL lines, a type III latency line, three EBV⁺ primary effusion lymphomas (PEL), and three AIDS-related diffuse large B-cell lymphomas (DLBCL) for expression of EBV-encoded miRNAs. A markedly elevated expression of miRNA BHRF1-3 in type III relative to its parental type I BL line was found. Primary unmanipulated type I BLs and EBV⁺ PELs expressed high levels of BART2 miRNA, whereas DLBCLs expressed both BART2 and BHRF1-3 species. BHRF1-3 miRNA expression inversely correlated with levels of a putative cellular target, the IFN-inducible T-cell attracting chemokine CXCL-11/I-TAC, and suppression of this factor was reversed by transfection of an antisense oligo to the EBV miRNA BHRF1-3. EBV-encoded miRNAs are expressed in primary lymphomas classically linked to the virus and are associated with the viral latency status. Targeted suppression of CXCL-11/I-TAC by a viral-encoded miRNA may serve as an immunomodulatory mechanism in these tumors. [Cancer Res 2008;68(5):1436–42]

MicroRNAs (miRNA) have emerged as key regulators of cell lineage differentiation and cancer. We used precursor miRNA profiling by a novel real-time QPCR method (i) to define progressive stages of endothelial cell transformation cumulating in Kaposi sarcoma (KS) and (ii) to identify specific miRNAs that serve as biomarkers for tumor progression. We were able to compare primary patient biopsies to well-established culture and mouse tumor models. Loss of mir-221 and gain of mir-15 expression demarked the transition from merely immortalized to fully tumorigenic endothelial cells. Mir-140 and Kaposi sarcoma–associated herpesvirus viral miRNAs increased linearly with the degree of transformation. Mir-24 emerged as a biomarker specific for KS. MicroRNAs are key regulators of cancer and development. We can use their pattern of expression to classify different cancers or in our case different stages in cancer development. We used a novel method to define progressive stages for Kaposi sarcoma (KS), which is a cancer of the endothelial cells. We identified specific precursor-miRNAs that accurately identify stages of KS tumor progression. For the first time, we were able to profile KS patient material. This is difficult to come by, but it is more closely related to the human cancer than even the best cell culture models. Our work statistically defined clusters of pre-miRNAs, each signifying one step in cancer progression. This is the first time that precursor miRNAs profiling was used to define cancer stages. It is also the first time that we have defined makers of any kind that allow us to distinguish between different types of the endothelial cancer KS. Loss of mir-221 precursor miRNA and gain of mir-15 precursor miRNA expression demarked the transition from merely immortal to fully tumorigenic cells. Mir-140 and Kaposi sarcoma–associated herpesvirus viral microRNAs increased progressively with the degree of transformation, i.e. more aggressive stages expressed higher levels of these biomarkers. High levels of the precursor microRNA mir-24 emerged as a biomarker only in patient derived KS samples, not in any of the culture models.

Several tools have been developed to evaluate HIV health-related quality of life (HRQoL) during and after antiretroviral therapy (ART). Few longitudinal studies evaluated the effect of ART on the quality of life of HIV patients. To evaluate changes in HRQoL in HIV-infected individuals one year after initiating ART. A prospective study was conducted from May 2016 to July 2018. Data on clinical and sociodemographic characteristics of 91 HIV-infected patients were collected prior to initiation of ART and one year thereafter. Demographic and clinical data were collected and the questionnaires 36-item Short Form Health Survey (SF-36) and HIV/AIDS-targeted quality of life (HAT-QoL) were administered in both periods. Asymptomatic individuals, aged ≥18 years, were included in the study. Patients who discontinued treatment were excluded. The association between predictors of physical and mental HRQoL was analyzed by multiple linear regression analysis. Patients were predominantly male (78.0%), mean age 35.3 ± 10.7 years, with no stable relationship (80.2%), and no comorbidities (73.6%). Most of the SF-36 domains improved after one year, particularly Physical Function (p = 0.0001), General Health (p = 0.0001), Social Functioning (p = 0.0001), Mental Health (p = 0.001), and Mental Component Summary (p = 0.004). HAT-QoL domains improved in the Overall Function (p = 0.0001), Life Satisfaction (p = 0.0001), Provider Trust (p = 0.001), and Sexual Function (p = 0.0001) domains. Sex (p = 0.032), age (p = 0.001), income (p = 0.007), and stable relationship (p = 0.004) were good predictors of the Physical Component Summary. Sex (p = 0.002) and stable relationship (p = 0.038) were good predictors of the Mental Component Summary. SF-36 and HAT-QoL scales presented strong correlations, except for Medication Concerns (0.15-0.37), HIV Mastery (0.18-0.38), Disclosure Worries (-0.15 to 0.07), and Provider Trust (-0.07 to 0.15). ART improved HRQoL after one year of use. The HAT-QoL and SF-36 correlated well and are good tools to evaluate HRQoL in HIV-infected patients on ART.

Patients with AIDS under antiretroviral therapy often present with metabolic problems associated with HIV infection and its therapy, which can affect their quality of life. The knowledge on the potential benefits of regular physical exercises for HIV-infected patients is limited. We conducted a clinical trial to evaluate the impact of regular physical activity on quality of life, anatomic disturbances, and/or metabolic changes in patients with AIDS in the city of Salvador, Brazil. Patients were randomly assigned in monthly workshops (1-hour duration) to discuss the importance of physical activity and receive nutritional counseling (control group) or to receive a 1-hour supervised gym class three times a week plus monthly nutritional counseling (intervention group). Before and after intervention, body composition, maximum oxygen consumption, metabolic equivalent, blood count, fasting total cholesterol, high-density lipoprotein, triglycerides, glucose, HIV viral load and CD4/CD8 counts, and resting heart rate were measured. Quality of life was evaluated at baseline and after 24 weeks. The domains of quality of life, general health, vitality and mental health increased in the exercise group (P < 0.05) compared with the control group. In the exercise group, fat mass (P = 0.04), the resting heart rate (P = 0.001), waist circumference (P = 0.002), and glucose (P = 0.003) decreased. Muscle mass (P = 0.002), CD4 T cells (P = 0.002), metabolic equivalent (P = 0.014), and maximum oxygen consumption (P = 0.05) increased. The practice of regular exercise, coupled with nutritional guidance, in individuals with HIV/AIDS significantly improves the quality of life.

(2018). Raltegravir versus lopinavir/ritonavir for treatment of HIV-infected late-presenting pregnant women. HIV Clinical Trials: Vol. 19, No. 3, pp. 94-100.

Introduction: Kaposi’s sarcoma (KS) remains the most frequent malignancy in persons living with HIV (PWH) in Latin America. We examined KS trends and outcomes from Latin American clinical sites in the era of increased access to antiretroviral therapy (ART).Methods: Cohorts in Brazil, Peru, Mexico, Honduras, Argentina and Chile contributed clinical data of PWH ≥16 years old from 2000 to 2017, excluding patients with KS diagnosed before clinic enrolment. We compared KS incidence over time using multivariable incidence rate ratios. Predictors of KS before/at or after ART initiation and of mortality after KS were examined using Cox regression.Results: Of 25 981 PWH, 481 had incident KS, including 200 ART‐naïve and 281 ART‐treated patients. From 2000 to 2017, the incidence of KS decreased from 55.1 to 3.0 per 1000 person‐years. In models adjusting for CD4 and other factors, the relative risk for KS decreased from 2000 to 2008. Since 2010, the adjusted risk of KS increased in the periods before and ≤90 days after ART initiation but decreased >90 days after ART. In addition to low CD4 and male‐to‐male sex, KS risk after ART was associated with age and history of other AIDS‐defining illnesses. Mortality after KS (approximately 25% after five years) was not associated with either year of KS diagnosis nor timing of diagnosis relative to ART initiation.Conclusions: KS incidence in Latin America has remained stable in recent years and risk is highest before and shortly after ART initiation. Early diagnosis of HIV and ART initiation remain critical priorities in the region.