Alterations in neurotransmitter levels and transcription factor expression following intranasal buprenorphine administration.

Buprenorphine is an opioid drug used in the management of pain and the treatment opioid addiction. Like other opioids, it is believed that it achieves these effects by altering functional neurotransmitter pathways and the expression of important transcription factors; cyclic AMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the brain. However, there is a lack of scientific evidence to support these theories. This study investigated the pharmacodynamic effects of BUP administration by assessing neurotransmitter and molecular changes in the healthy rodent brain. Sprague-Dawley rats (150-200 g) were intranasally administered buprenorphine (0.3 mg/mL) and sacrificed at different time points: 0.25, 0.5, 1, 2, 4, 6, 8 and 24 h post drug administration. LC-MS was used to quantify BUP and neurotransmitters (GABA, GLUT, DA, NE and 5-HT) in the brain, while CREB and BDNF gene expression was determined using qPCR. Results showed that BUP reached a Cmax of 1.21 ± 0.0523 ng/mL after 2 h, with all neurotransmitters showing an increase in their concentration over time, with GABA, GLUT and NE reaching their maximum concentration after 8 h. DA and 5-HT reached their maximum concentrations at 1 h and 24 h, respectively post drug administration. Treatment with BUP resulted in significant upregulation in BDNF expression throughout the treatment period while CREB showed patterns of significant upregulation at 2 and 8 h, and downregulation at 1 and 6 h. This study contributes to the understanding of the pharmacodynamic effects of BUP in opioid addiction by proving that the drug significantly influences NT pathways that are implicated in opioid addiction.

Evaluating DREAMS HIV prevention interventions targeting adolescent girls and young women in high HIV prevalence districts in South Africa: protocol for a cross-sectional study.

BACKGROUND: Young women in sub-Saharan Africa remain at the epicentre of the HIV epidemic, with surveillance data indicating persistent high levels of HIV incidence. In South Africa, adolescent girls and young women (AGYW) account for a quarter of all new HIV infections. Determined, Resilient, Empowered, AIDS-free, Mentored and Safe (DREAMS) is a strategy introduced by the United States President's Emergency Plan for AIDS Relief (PEPFAR) aimed at reducing HIV incidence among AGYW in 10 countries in sub-Saharan Africa by 25% in the programme's first year, and by 40% in the second year. This study will assess the change in HIV incidence and reduction in risk associated behaviours that can be attributed to the DREAMS initiative in South Africa, using a population-based cross-sectional survey. METHODS: Data will be collected from a household-based representative sample of AGYW (between the ages 12-24 years) in four high prevalence districts (more than 10% of the population have HIV in these districts) in South Africa in which DREAMS has been implemented. A stratified cluster-based sampling approach will be used to select eligible participants for a cross-sectional survey with 18,500, to be conducted over 2017/2018. A questionnaire will be administered containing questions on sexual risk behaviour, selected academic and developmental milestones, prevalence of gender based violence, whilst examining exposure to DREAMS programmes. Biological samples, including two micro-containers of blood and self-collected vulvovaginal swab samples, are collected in each survey to test for HIV infection, HIV incidence, sexually transmitted infections (STIs) and pregnancy. This study will measure trends in population level HIV incidence using the Limiting antigen (LAg) Avidity Enzyme Immuno-Assay (EIA) and monitor changes in HIV incidence. DISCUSSION: Ending the HIV/AIDS pandemic by 2030 requires the continual monitoring and evaluation of prevention programmes, with the aim of optimising efforts and ensuring the achievement of epidemic control. This study will determine the impact DREAMS interventions have had on HIV incidence among AGYW in a 'real world, non-trial setting'.

Health expenditure and catastrophic spending among older adults living with HIV.

INTRODUCTION: The burden of HIV is increasing among adults aged over 50, who generally experience increased risk of cormorbid illnesses and poorer financial protection. We compared patterns of health utilisation and expenditure among HIV-positive and HIV-negative adults over 50. METHODS: Data were drawn from the Study on global AGEing and adult health in South Africa with analysis focusing on individual and household-level data of 147 HIV-positive and 2725 HIV-negative respondents. RESULTS: HIV-positive respondents reported lower utilisation of private health-care facilities (11.8%) than HIV-negative respondents (25.0%) (p = .03) and generally had more negative attitudes towards health system responsiveness than HIV-negative counterparts. Less than 10% of HIV-positive and HIV-negative respondents experienced catastrophic health expenditure (CHE). Women (OR 1.8; p < .001) and respondents from rural settings (OR 2.9; p < .01) had higher odds of CHE than men or respondents in urban settings. Over half the respondents in both groups indicated that they had received free health care. CONCLUSIONS: These findings suggest that although HIV-positive and HIV-negative older adults in South Africa are protected to some extent from CHE, inequalities still exist in access to and quality of care available at health-care services - which can inform South Africa's development of a national health insurance scheme.

Verification of chemistry reference ranges using a simple method in sub-Saharan Africa.

BACKGROUND: Chemistry safety assessments are interpreted by using chemistry reference ranges (CRRs). Verification of CRRs is time consuming and often requires a statistical background. OBJECTIVES: We report on an easy and cost-saving method to verify CRRs. METHODS: Using a former method introduced by Sigma Diagnostics, three study sites in sub-Saharan Africa, Bondo, Kenya, and Pretoria and Bloemfontein, South Africa, verified the CRRs for hepatic and renal biochemistry assays performed during a clinical trial of HIV antiretroviral pre-exposure prophylaxis. The aspartate aminotransferase/alanine aminotransferase, creatinine and phosphorus results from 10 clinically-healthy participants at the screening visit were used. In the event the CRRs did not pass the verification, new CRRs had to be calculated based on 40 clinically-healthy participants. RESULTS: Within a few weeks, the study sites accomplished verification of the CRRs without additional costs. The aspartate aminotransferase reference ranges for the Bondo, Kenya site and the alanine aminotransferase reference ranges for the Pretoria, South Africa site required adjustment. The phosphorus CRR passed verification and the creatinine CRR required adjustment at every site. The newly-established CRR intervals were narrower than the CRRs used previously at these study sites due to decreases in the upper limits of the reference ranges. As a result, more toxicities were detected. CONCLUSION: To ensure the safety of clinical trial participants, verification of CRRs should be standard practice in clinical trials conducted in settings where the CRR has not been validated for the local population. This verification method is simple, inexpensive, and can be performed by any medical laboratory.

Strengthening HIV surveillance in the antiretroviral therapy era: rationale and design of a longitudinal study to monitor HIV prevalence and incidence in the uMgungundlovu District, KwaZulu-Natal, South Africa.

BACKGROUND: South Africa has over 6,000,000 HIV infected individuals and the province of KwaZulu-Natal (KZN) is the most severely affected. As public health initiatives to better control the HIV epidemic are implemented, timely, detailed and robust surveillance data are needed to monitor, evaluate and inform the programmatic interventions and policies over time. We describe the rationale and design of the HIV Incidence Provincial Surveillance System (HIPSS) to monitor HIV prevalence and incidence. METHODS/DESIGN: The household-based survey will include a sample of men and women from two sub-districts of the uMgungundlovu municipality (Vulindlela and the Greater Edendale) of KZN, South Africa. The study is designed as two sequential cross-sectional surveys of 10,000 randomly selected individuals aged 15-49 years to be conducted one year apart. From the cross sectional surveys, two sequential cohorts of HIV negative individuals aged 15-35 years will be followed-up one year later to measure the primary outcome of HIV incidence. Secondary outcomes include the laboratory measurements for pulmonary tuberculosis, sexually transmitted infections and evaluating tests for estimating population-level HIV incidence. Antiretroviral therapy (ART) access, HIV-1 RNA viral load, and CD4 cell counts in HIV positive individuals will assess the effectiveness of the HIV treatment cascade. Household and individual-level socio-demographic characteristics, exposure to HIV programmatic interventions and risk behaviours will be assessed as predictors of HIV incidence. The incidence rate ratio of the two cohorts will be calculated to quantify the change in HIV incidence between consecutive samples. In anticipation of better availability of population-level HIV prevention and treatment programmes leading to decreases in HIV incidence, the sample size provides 84% power to detect a reduction of 30% in the HIV incidence rate between surveys. DISCUSSION: The results from HIPSS will provide critical data regarding HIV prevalence and incidence in this community and will establish whether HIV prevention and treatment efforts in a "real world", non-trial setting have an impact on HIV incidence at a population level. Importantly, the study design and methods will inform future methods for HIV surveillance.

Prevalence of HIV and chronic comorbidities among older adults.

OBJECTIVES: Limited evidence is available on HIV, aging and comorbidities in sub-Saharan Africa. This article describes the prevalence of HIV and chronic comorbidities among those aged 50 years and older in South Africa using nationally representative data. DESIGN: The WHO's Study of global AGEing and adult health (SAGE) was conducted in South Africa in 2007-2008. SAGE includes nationally representative cohorts of persons aged 50 years and older, with comparison samples of those aged 18-49 years, which aims to study health and its determinants. METHODS: Logistic and linear regression models were applied to data from respondents aged 50 years and older to determine associations between age, sex and HIV status and various outcome variables including prevalence of seven chronic conditions. RESULTS: HIV prevalence among adults aged 50 and older in South Africa was 6.4% and was particularly elevated among Africans, women aged 50-59 and those living in rural areas. Rates of chronic disease were higher among all older adults compared with those aged 18-49. Of those aged 50 years and older, 29.6% had two or more of the seven chronic conditions compared with 8.8% of those aged 18-49 years (P < 0.0001). When controlling for age and sex among those aged 50 and older, BMI was lower among HIV-infected older adults aged 50 and older (27.5 kg/m2) than in HIV-uninfected individuals of the same age (30.6) (P < 0.0001). Grip strength among HIV-infected older adults was significantly (P=0.004) weaker than among similarly-aged HIV-uninfected individuals. CONCLUSION: HIV-infected older adults in South Africa have high rates of chronic disease and weakness. Studies are required to examine HIV diagnostics and treatment instigation rates among older adults to ensure equity of access to quality care, as the number and percentage of older adults living with HIV is likely to increase.

The epidemiology of HIV in South African workplaces.

OBJECTIVE: To determine the prevalence and distribution of HIV in South African workplaces. DESIGN: : Cross-sectional HIV prevalence and knowledge, attitudes and practices surveys, conducted in 22 public and private sector organizations in all nine provinces of South Africa on full-time, formally employed personnel who provided consent to participate. OUTCOME MEASURES: The primary outcome was HIV prevalence. RESULTS: The crude HIV prevalence among the 32 015 participants was 10.9%. HIV prevalence was higher among men (11.3%) than among women (9.8%) and among black Africans (16.6%) than among other race groups (2.7%). Although managers and employees with post-school education had a lower HIV prevalence than lower skilled employees, this only partly accounted for the race differences. CONCLUSION: The HIV prevalence within an organization is not entirely explained by the race, age and sex structure of the workforce. This indicates that there is some other factor that is associated with the organization and has an impact on HIV prevalence.

Carraguard Vaginal Gel Safety in HIV-Positive Women and Men in South Africa.

OBJECTIVE: To assess the safety of the candidate microbicide Carraguard gel in HIV-positive women and men. DESIGN: A randomized, placebo-controlled, triple-blinded clinical trial of Carraguard gel when applied vaginally once per day for 14 intermenstrual days by sexually abstinent and sexually active HIV-positive women; and when applied directly to the penis once per day for 7 days by sexually abstinent HIV-positive men. METHODS: In each cohort (n = 20 per cohort), participants were randomized to Carraguard, methylcellulose placebo, or no product (1:1:1). In addition to traditional microbicide trial safety endpoints, the effects of microbicide use on vaginal shedding of HIV-1 RNA and markers of genital inflammation, epithelial sloughing, and microhemorrhage were also explored. RESULTS: Gel compliance was high in both gel-use groups in the 3 cohorts. Carraguard use was not associated with abnormal genital findings, other abnormal clinical findings, markers of genital inflammation, epithelial sloughing or microhemorrhage, or self-reported symptoms in women and men, or with abnormal vaginal flora or genital shedding of HIV-1 RNA in women. Adverse events were mostly mild, not attributed to gel use, and similarly distributed between groups. CONCLUSIONS: Once-daily use of Carraguard for 7 to 14 days appeared to be safe in HIV-positive women and men.