Is the Sexual Behaviour of HIV Patients on Antiretroviral therapy safe or risky in Sub-Saharan Africa? Meta-Analysis and Meta-Regression

BACKGROUND: Reports on the sexual behavior of people on antiretroviral therapy (ART) are inconsistent. We selected 14 articles that compared the sexual behavior of people with and without ART for this analysis. METHODS: We included both cross-sectional studies that compared different ART-naïve and ART-experienced participants and longitudinal studies examining the behavior of the same individuals pre- and post-ART start. Meta-analyses were performed both stratified by type of study and combined. Outcome variables assessed for association with ART experience were any sexual activity, unprotected sex and having multiple sexual partners. Random-effect models were applied to determine the overall odds ratios. Sub-group analyses and meta-regression analyses were performed to examine sources of heterogeneity among the studies. Sensitivity analysis was also conducted to evaluate the stability of the overall odds ratio in the presence of outliers. RESULTS: The meta-analysis failed to show a statistically significant association of any sexual activity with ART experience. It did, however, show an overall statistically significant reduction of any unprotected sex, having multiple sexual partners and unprotected sex with HIV negative or unknown HIV status with ART experience. Meta-regression showed no interaction between duration of ART use or recall period of sexual behavior with the sexual activity variables. However, there was an association between the percentage of married or cohabiting participants included in a study and reductions in the practice of unprotected sex with ART. CONCLUSION: In general, this meta-analysis demonstrated a significant reduction in risky sexual behavior among people on ART in sub-Saharan Africa. Future studies should investigate the reproducibility and continuity of the observed positive behavioural changes as the duration of ART lasts a decade or more

Magnitude of Antiretroviral Drug toxicity in adult HIV patients in Ethiopia: A cohort study at seven teaching hospitals

Background: The introduction of antiretroviral therapy (ART) has resulted in significant mortality reduction and improvement in the quality of life. However, this has come at a cost of increased drug toxicity. The objective of this study was to assess the patterns and predictors of ART toxicity in adult HIV patients in Ethiopia.Methods: This is a prospective cohort study conducted at seven teaching hospitals between September 2009 and December 2013 involving 3921 HIV patients on ART. Adverse drug reactions (ADR) due to ART were identified based on clinical assessment and/or laboratory parameters. Multivariable random effects Poisson regression analysis was used to identify factors independently associated with toxicity.Result: ADR due to ART drugs was reported in 867 (22.1 %) of the participants; 374 (9.5%) had severe forms. About 87% of reported toxicities were limited to three organ systems – the skin, nervous system and blood. The overall incidence of ADR was 9 per 100 person years. About a third of toxicities occurred during the first six months after ART initiation with the incidence rate of 22.4 per 100 person years. Concomitant anti-tuberculosis treatment was the strongest independent predictor of toxicity.Conclusion: ADR was found to be highly prevalent in HIV patients on ART at tertiary hospitals in Ethiopia. Most of these conditions occurred early after ART initiation and in those with concomitant anti-tuberculosis treatment. Thus, routine monitoring of patients on ART should be strengthened with particular emphasis in the first 6 months. Strategies should also be devised to replace older and more toxic agents with newer and safer drugs available.Key words: HIV, ART, adverse drug reaction, incidence rate, ACM, Ethiopi

A Meta-Analysis of Risky Sexual Behaviour among Male Youth in Developing Countries

The purpose of this meta-analysis was to assess the association between risky sexual behaviour and level of education and economic status in male youth. Previous tests of the association of risky sexual behaviour with levels of education and economic status have yielded inconsistent results. Using data from 26 countries, from both within and outside Africa, we performed a meta-analysis with a specific focus on male youths’ risky sexual behaviour. We applied a random effects analytic model and calculated a pooled odds ratio. Out of 19,148 males aged 15–24 years who reported having sexual intercourse in the 12 months preceding the survey, 75% engaged in higher-risk sex. The proportion of higher-risk sex among male youth aged 15–19 years was nearly 90% in 21 of the 26 countries. The pooled odds ratio showed a statistically significant association of higher-risk sex with male youth younger than 20 years, living in urban centers, well educated, and of a high economic status. The overall proportion of condom use during youths’ most recent higher-risk sexual encounter was 40% and 51% among 15–19-year-olds and 20–24-year-olds, respectively. Our findings suggest that male youth’s socioeconomic status is directly related to the likelihood that they practice higher-risk sex. The relationship between income and sexual behaviour should be explored further

Virologic response to tipranavir-ritonavir or darunavir-ritonavir based regimens in antiretroviral therapy experienced HIV-1 patients: a meta-analysis and meta-regression of randomized controlled clinical trials.

The development of tipranavir and darunavir, second generation non-peptidic HIV protease inhibitors, with marked improved resistance profiles, has opened a new perspective on the treatment of antiretroviral therapy (ART) experienced HIV patients with poor viral load control. The aim of this study was to determine the virologic response in ART experienced patients to tipranavir-ritonavir and darunavir-ritonavir based regimens.A computer based literature search was conducted in the databases of HINARI (Health InterNetwork Access to Research Initiative), Medline and Cochrane library. Meta-analysis was performed by including randomized controlled studies that were conducted in ART experienced patients with plasma viral load above 1,000 copies HIV RNA/ml. The odds ratios and 95% confidence intervals (CI) for viral loads of <50 copies and <400 copies HIV RNA/ml at the end of the intervention were determined by the random effects model. Meta-regression, sensitivity analysis and funnel plots were done. The number of HIV-1 patients who were on either a tipranavir-ritonavir or darunavir-ritonavir based regimen and achieved viral load less than 50 copies HIV RNA/ml was significantly higher (overall OR = 3.4; 95% CI, 2.61-4.52) than the number of HIV-1 patients who were on investigator selected boosted comparator HIV-1 protease inhibitors (CPIs-ritonavir). Similarly, the number of patients with viral load less than 400 copies HIV RNA/ml was significantly higher in either the tipranavir-ritonavir or darunavir-ritonavir based regimen treated group (overall OR = 3.0; 95% CI, 2.15-4.11). Meta-regression showed that the viral load reduction was independent of baseline viral load, baseline CD4 count and duration of tipranavir-ritonavir or darunavir-ritonavir based regimen.Tipranavir and darunavir based regimens were more effective in patients who were ART experienced and had poor viral load control. Further studies are required to determine their consistent viral load suppression effect as the duration of treatment is more prolonged

Stiffness: a master regulator of fibrogenesis?

© 2019 Dr. Asres Berhan MitkeFibrosis is one of the leading causes of death that may affect all organs in the human body. All forms of fibrosis are characterized by fibrotic scarring resulting from replacement of normal tissue with extracellular matrix (ECM). Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonias; it is relentlessly progressive and ultimately fatal. The aberrant accumulation of myofibroblasts and the excessive deposition of ECM are the main features of IPF. The suggested sources of myofibroblasts include resident lung fibroblasts, lipofibroblasts, epithelial-mesenchymal transition (EMT), endothelial-mesenchymal transition (EndoMT) and recruitment from circulating fibrocytes. Lipofibroblasts are lipid-droplet containing cells, which have a key role in maintaining homeostasis of the lung. However, IPF patients have stiffer lungs and homeostatically dysregulated cellular microenvironments. Stiff substrates are known to augment myofibroblast differentiation, ECM production and the activation of the prototype profibrotic cytokine, transforming growth factor β1 (TGF-β1). In contrast, stiff substrates inhibit cyclooxygenase-2 (COX-2) expression and the synthesis of the anti-fibrotic prostanoid, prostaglandin E2 (PGE2). This thesis for the first time revealed a reduction in the lipofibroblast population and prostaglandin E synthase (PTGES) level in the lungs of IPF patients. This current study also highlighted the significance of dimensionality in modulating fibroblast behavior by establishing human lung fibroblasts in 2D soft and 3D soft microenvironments (that have similar stiffness) and performing head-to-head comparisons with the conventional 2D stiff cultures. Our data demonstrated the marked suppression of fibroblast proliferation and fibrogenesis in 3D soft microenvironment, as contrasted with 2D soft, independent of differences in prostanoid levels. This thesis also presented evidence that suggested the augmented anti-fibrogenic actions of glucocorticoid and PGE2 combination. Within this thesis, I showed that the phenotypic plasticity of fibroblasts depends on substrate stiffness and dimensionality. The level of lipid-droplet inclusions that mark the formation of lipofibroblasts was remarkably increased in 3D fibroblasts. In 2D soft and 3D microenvironments, striking reductions of the myofibroblast marker, alpha smooth muscle actin (ACTA2) and increases in the lipofibroblast markers, adipose differentiation-related protein (ADRP) were observed. Activated exogenous TGF-β1, despite elevating expression of the fibrogen interleukin-11 (IL-11), did not induce the differentiation of lipofibroblast into myofibroblasts in 2D soft 3D soft settings. This study has not only provided insight into fibroblast phenotypic plasticity, but has also revealed a novel role of parathyroid hormone-related protein (PTHrP), as a main effector in mediating the effects of softness or dimensionality on fibroblast phenotypic plasticity. Moreover, this study has established the anti-fibrogenic actions of PTHrP in lung fibroblasts in vitro

Mantel-Haenszel odds ratio of ART experienced HIV-1 patients who achieved HIV-1 RNA < 50 copies per ml (TPV/r or DRV/r vs CPIs/r).

<p>Mantel-Haenszel odds ratio of ART experienced HIV-1 patients who achieved HIV-1 RNA < 50 copies per ml (TPV/r or DRV/r vs CPIs/r).</p

Mantel-Haenszel odds ratio of ART experienced HIV-1 patients with HIV-1 RNA reduction ≥1 log₁₀ copies/ml from baseline (TPV/r or DRV/r vs CPIs/r).

<p>Mantel-Haenszel odds ratio of ART experienced HIV-1 patients with HIV-1 RNA reduction ≥1 log₁₀ copies/ml from baseline (TPV/r or DRV/r vs CPIs/r).</p

Summary of findings from meta-regression analyses.

<p>Summary of findings from meta-regression analyses.</p