Depression in the Pathway of HIV Antiretroviral Effects on Sexual Risk Behavior Among Patients in Uganda

HIV antiretroviral therapy (ART) can increase safe sex or lead to disinhibition and less condom use. We conducted one of the first controlled studies of ART effects on sexual risk behavior in sub-Saharan Africa, and the potential explanatory roles of physical and mental health. Participants (302 non-ART, 300 ART) were followed for the first 12?months of HIV care in Uganda. Multivariate intention-to-treat regression analysis showed that frequency of sex increased significantly in both groups, but more among ART patients; when added to the model in separate analyses, changes in physical health functioning and depression were both significant predictors, as was time in HIV care, but there was no longer an ART effect. Both ART and non-ART groups had similar dramatic increases in consistent condom use over time; however, change in depression, unlike physical health functioning, was a significant predictor of consistent condom use when added to this model, and there remained a similar level of increased condom use among ART and non-ART patients. HIV care and ART increase sexual activity and condom use, but depression undercuts the prevention benefits of ART, highlighting the need to integrate mental health services into HIV care.     

A Human-Centered Approach to CV Care: Infrastructure Development in Uganda

In this case study, we describe an ongoing approach to develop sustainable acute and chronic cardiovascular care infrastructure in Uganda that involves patient and provider participation. Leveraging strong infrastructure for HIV/AIDS care delivery, University Hospitals Harrington Heart and Vascular Institute and Case Western Reserve University have partnered with U.S. and Ugandan collaborators to improve cardiovascular capabilities. The collaboration has solicited innovative solutions from patients and providers focusing on education and advanced training, penicillin supply, diagnostic strategy (e.g., hand-held ultrasound), maternal health, and community awareness. Key outcomes of this approach have been the completion of formal training of the first interventional cardiologists and heart failure specialists in the country, establishment of 4 integrated regional centers of excellence in rheumatic heart disease care with a national rheumatic heart disease registry, a penicillin distribution and adherence support program focused on retention in care, access to imaging technology, and in-country capabilities to treat advanced rheumatic heart valve disease.     

Implementation of an antiretroviral access program for HIV-1-infected individuals in resource-limited settings: clinical results from 4 African countries

BACKGROUND: We assessed the effectiveness and safety of highly active antiretroviral therapy (HAART) in HIV-1-infected patients in resource-limited African countries. HIV-1 screening, therapy, counseling, monitoring, training, and education were provided free of charge. METHODS: In an open-label cohort program, 206 antiretroviral-naive HIV-1-infected patients who could not afford HAART were recruited in 4 urban clinics in Senegal, C?te d'Ivoire, Uganda, and Kenya and were treated with saquinavir boosted with ritonavir (1600/100 mg once daily), lamivudine (150 mg twice daily), and zidovudine (300 mg twice daily). The primary outcome was a plasma viral load (pVL) of <400 copies/mL after 96 weeks of treatment. Secondary analyses included CD4 cell count changes and the occurrence of treatment-emergent adverse events. RESULTS: The median age of the patient group was 36 years, 38% were male, 35% of the patients had AIDS, the median CD4 count was 119 cells/microL, and the median pVL was 304,210 copies/mL. Overall, 65%/52% (on treatment [OT]/intent to treat [ITT]) of the patients had a pVL <400 copies/mL after 96 weeks of follow-up. This proportion varied significantly between sites, however; although in Nairobi and Dakar, 51%/40% and 56%/46% (OT/ITT) were found, respectively, Abidjan and Kampala showed proportions of 69%/54% and 83%/69% (OT/ITT), respectively. The median increase in the CD4 count was 198 cells/microL (interquartile range: 86-319 cells/microL), ranging from 191 to 292 cells/microL between the sites. Fourteen patients (6.8%) died between 8 and 96 weeks of follow-up, whereas 18 (9%) developed an AIDS-defining event between 8 and 96 weeks of follow-up. Non-HIV-related serious adverse events occurred in 55 patients (26.7%), of whom 13 were diagnosed with severe anemia. Thirty-five patients (17%) changed treatment for toxicity reasons. CONCLUSIONS: Although a statistically significant difference was observed between sites with respect to virologic success, overall virologic and immunologic responses to HAART in resource-limited African settings can be as good as in Western settings. There were some difficulties (eg, laboratory, logistics, proper training) during the early phase of the program. Therefore, provision of adequate medical care, counseling, proper instruction, and education of patients and medical staff during the entire study is warranted in such programs, with special care in the early phase.     

Rational identification of a novel peptide for targeting nanocarriers to 9L glioma

Traditional therapies for high grade gliomas are limited in part by collateral damage to normal tissues. Selective delivery of therapies to tumors is, therefore, needed. Here, we report that liposomal nanocarriers coated with a novel oligopeptide enhance uptake by 9L gliosarcoma. A targeting nine amino acid peptide sequence (RSI) was identified by differential panning of random peptide phage display libraries on 9L cells and rat blood cells and plasma. Peptides were coupled to the surface of liposomal nanocarriers which were subsequently loaded with doxorubicin. The ability of RSI coated liposomes to facilitate drug uptake and cytotoxicity was compared with conventional liposomal nanocarriers and controls. In addition, plasma clearance profiles of the RSI peptide coupled liposomal nanocarriers were evaluated in adult immuno-competent rats. RSI peptide-coupled liposomal nanocarriers enhanced drug uptake by 9L cells by 500% compared with conventional liposomal nanocarriers, and significantly increased cytotoxicity. The plasma half-lives confirmed that the presence of the RSI peptide on the liposomal nanocarriers did not compromise circulation time in the blood in comparison with Stealth liposomal nanocarriers. These data suggest that phage-identified oligopeptides could lead to the development of new tumor selective nanocarriers.     

Eating away from home is associated with overweight and obesity among Ugandan adults: the 2014 Uganda non-communicable disease risk factor survey

BACKGROUND/OBJECTIVESWe investigated the associations between eating away from home (EAFH) and overweight and obesity among Ugandan adults using the 2014 Uganda non-communicable disease risk factor survey.SUBJECTS/METHODSIn total, 3,025 participants aged 18–69 years were included in the analysis. The frequency of EAFH was assessed by asking participants the number of meals eaten per week that were not prepared at a home. EAFH frequency was categorized as; less than once/week, 1-2 times/week, or ≥ 3 times/week. Logistic regression was used to evaluate the associations between overweight, obesity, and EAFH. We also tested whether sex and age modified these associations.RESULTSParticipants that ate away from home ≥ 3 times/week were 2.13 times more likely to be obese than those that ate away from home less than once/week (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.28–3.54). However, when the analysis was stratified by sex, women that ate away from home ≥ 3 times/week were 42% less likely to be overweight than those that ate away from home less than once/week (OR, 0.58; 95% CI, 0.36–0.94). Men that ate away from home ≥ 3 times a week were 3.89 times and 2.23 times more likely to be obese and overweight, respectively, than those that ate away from home less than once/week (obesity: OR, 3.89; 95% CI, 1.50–10.09; overweight: OR, 2.23; 95% CI, 1.42–3.51). Age-stratified analysis showed that among participants aged 31–50 years, those that ate away from home ≥ 3 times a week were 3.53 times more likely to be obese than those that ate away from home less than once/week (OR, 3.53; 95% CI, 1.69–7.37).CONCLUSIONSFrequent EAFH was positively associated with overweight and obesity among men, and obesity among young/middle-aged adults, but negatively associated with overweight in women. Nutritional interventions for obesity reduction in Uganda should include strategies aimed at reducing the frequency of eating meals prepared away from home, and specifically target men and young/middle-aged adults.     

Resistance to antiretroviral therapy among patients in Uganda

OBJECTIVE: To characterize HIV-1 phenotypic resistance patterns and genotypic mutations among patients taking antiretroviral medications in Uganda. METHODS: We reviewed charts and retrieved archived plasma specimens from patients at an AIDS specialty center in Uganda where antiretroviral therapy has been used since 1996. Phenotypic and genotypic resistance testing was done on specimens associated with a viral load of 1000 copies/ml. RESULTS: Resistance testing of specimens was completed for 16 patients. Among 11 specimens collected before initiation of antiretroviral therapy, no phenotypic resistance or primary genotypic mutations were found. Among 8 patients taking lamivudine, phenotypic resistance was found for 9 (90%) of 10 specimens and was associated with an M184V mutation in all nine cases. Among 12 patients taking zidovudine, no phenotypic resistance and few primary mutations were found. For 6 patients who were receiving protease inhibitors, we observed no phenotypic resistance and only one primary genotypic mutation associated with resistance. CONCLUSIONS: The absence of apparent resistance among samples collected before antiretroviral therapy supports the notion that a similar approach to selection of antiretroviral therapy can generally be used against non-B subtypes. A genotypic marker of antiretroviral resistance to lamivudine in HIV-1 subtypes A, C, and D was similar to those in subtype B infections. These results suggest that the methods used for monitoring for the emergence of drug resistance in antiretroviral programs in Africa may be similar to those used in developed settings.