Michael J. A. Reid

Approaches to tuberculosis screening and diagnosis in people with HIV in resource-limited settings

Tuberculosis is the main cause of morbidity and mortality in people living with HIV/AIDS worldwide. Early diagnosis and treatment is essential to addressing the dual epidemic of tuberculosis and HIV. Increasing recognition of the importance of integrating tuberculosis services--including screening--into HIV care has led to global policies and the beginnings of implementation of joint activities at the national level. However, debate remains about the best methods of screening for pulmonary tuberculosis among people living with HIV/AIDS in resource-limited settings. Mycobacterial culture, the gold standard for tuberculosis diagnosis, is too slow and complex to be a useful screening test in such settings. More widely available methods, such as symptom screening, sputum smear microscopy, chest radiography, and tuberculin skin testing have important shortcomings, especially in people living with HIV/AIDS. However, until simpler, cheaper, and more sensitive diagnostics for tuberculosis are available in peripheral healthcare settings, a strategy must be developed that uses current evidence to combine available screening tools.

Cannabinoid-induced alterations in brain disposition of drugs of abuse.

Marijuana contains a complex mixture of compounds including tetrahydrocannabinol (THC), the major psychoactive constituent, and cannabidiol (CBD), a nonpsychoactive constituent. We have shown previously that CBD pretreatment of mice increases brain levels of THC and have now further characterized this effect and determined whether the brain pharmacokinetics of other drugs are also affected. CBD pretreatment of mice (30-60 min) increased brain levels of THC nearly 3-fold, whereas CBD co-administration did not. Because marijuana is often consumed with other drugs, the influence of cannabinoids on the brain levels of several other drugs of abuse was also determined. CBD pretreatment of mice increased brain levels (2- to 4-fold) of subsequently administered cocaine as well as phencyclidine (PCP). Although CBD pretreatment increased blood and brain levels of cocaine comparably, blood levels of PCP were only modestly elevated (up to 50%). Behavioral tests indicated that the CBD-mediated increases in the brain levels of THC, cocaine, and PCP correlated with increased pharmacological responses. Pretreatment with THC instead of CBD could similarly increase brain levels of cocaine, PCP, and CBD, although with a lower potency than CBD. On the other hand, pretreatment of mice with CBD had no effect on the brain levels of several other drugs of abuse including morphine, methadone, or methylenedioxyphenyl-methamphetamine. These findings demonstrate that cannabinoids can increase the brain concentrations and pharmacological actions of several other drugs of abuse, thereby providing a biochemical basis for the common practice of using marijuana concurrently with such drugs.

Diagnosing Balamuthia mandrillaris Encephalitis With Metagenomic Deep Sequencing

Identification of a particular cause of meningoencephalitis can be challenging owing to the myriad bacteria, viruses, fungi, and parasites that can produce overlapping clinical phenotypes, frequently delaying diagnosis and therapy. Metagenomic deep sequencing (MDS) approaches to infectious disease diagnostics are known for their ability to identify unusual or novel viruses and thus are well suited for investigating possible etiologies of meningoencephalitis.

Implementation of tuberculosis infection control measures at HIV care and treatment sites in sub-Saharan Africa.

SETTING A total of 663 human immunodeficiency virus (HIV) care and treatment sites in nine tuberculosis (TB) affected African countries, serving over 900,000 persons living with HIV. OBJECTIVE To determine the implementation of infection control (IC) measures and whether program and facility characteristics were associated with implementation of these measures. DESIGN A survey was conducted to assess the presence of a TB IC plan, triage practices for TB suspects, location of sputum collection and availability of particulate respirators. The association of facility characteristics with IC measures was examined using bivariate and multivariate methods. RESULTS Forty-seven per cent (range across countries [RAC] 2-77%) of sites had written TB IC plans; 60% (RAC 5-93%) practiced triage; of those with access to microscopy, 83% (RAC 59-91%) performed sputum collection outdoors and 13% (RAC 0-36%) in ventilated indoor rooms; 16% (RAC 1-87%) had particulate respirators available. Sites providing anti-tuberculosis treatment were more likely to have written IC plans (54% vs. 12%, P < 0.0001) and particulate respirators (18% vs. 8%, P = 0.0126), and to perform TB triage (65% vs. 40%, P = 0.0001) than those without anti-tuberculosis treatment services. CONCLUSIONS To protect HIV-infected patients and health care workers, there is an urgent need to scale up IC practices at HIV care and treatment sites, particularly at sites without anti-tuberculosis treatment services.

TB diagnostic capacity in sub-Saharan African HIV care settings.

Abstract:As HIV care services continue to scale-up in sub-Saharan Africa, adequate tuberculosis diagnostic capacity is vital to reduce mortality among HIV-infected persons. A structured survey was administered at 663 health facilities providing HIV care to 908,043 patients in across 9 sub-Saharan African countries to estimate the proportion of facilities and HIV patients at these facilities with access TB-related diagnostic tests. Sputum smear microscopy was available at 87% of facilities (representing 97% of patients), chest x-ray at 26% of facilities (representing 56% of patients), tuberculin skin tests were available at 12% of facilities (representing 33% of patients). Acid-fast bacillus culture was available on-/off-site at 53% of facilities (representing 77% of patients). Primary health facilities had lower availability of tuberculosis diagnostic tests compared with secondary and tertiary health facilities. As HIV care continues to decentralize to primary health facilities, a corresponding expansion of diagnostic capacity to lower levels of the health system will be essential.

New Models for Medical Education: Web-Based Conferencing to Support HIV Training in Sub-Saharan Africa

BACKGROUND Healthcare workers in Africa managing human immunodeficiency virus (HIV)-infected patients often receive inadequate HIV-specific medical education. The acceptability and feasibility of Web-based distance learning tools to enhance HIV training in Africa have not been extensively evaluated. MATERIALS AND METHODS In this prospective observational study, we assessed the feasibility of Web-conferencing to deliver HIV-specific medical training to clinicians supporting HIV care and treatment across 12 Sub-Saharan African countries over a 10-month period. Webinar attendance, technical quality, and participant satisfaction were measured for each Webinar. Demographic details about participants were recorded. RESULTS Attendance increased from 40 participants in Month 1 to over 160 in Month 10. Thirty-six percent of participants were physicians, and 21% were in allied health professions. A mean of 95% of respondents found the content to be relevant. Participants reported that the opportunity to interact with HIV clinicians from other countries and expert teaching from leading scientists were major reasons for attendance. Audio quality was variable across countries and over time. Barriers to attendance included lack of information technology (IT) literacy and Internet connectivity. CONCLUSIONS This analysis demonstrates that Webinars are feasible and acceptable to support HIV training. Significant impediments to scale up in use of Web-conferencing for HIV education in resource-limited settings include lack of IT hardware and limited IT literacy. Strengthening IT capacity and Internet infrastructure is necessary to support expanded use of Webinars as a tool for continuing HIV education.

Opinions and attitudes of participants in a randomized controlled trial examining the efficacy of SMS reminders to enhance antiretroviral adherence: a cross-sectional survey.

In sub-Saharan Africa antiretroviral therapy (ART) has significantly reduced mortality and morbidity of people living with HIV/AIDS. However incomplete treatment adherence - leading to treatment failure development of drug resistance and HIV disease progression - remains a major concern. Evidence suggests that adherence among individuals in sub-Saharan African declines over time and increasing mobile phone ownership across southern Africa has raised the possibility that text messages using SMS can be used to improve ART adherence. Given varying data about SMS interventions the authors sought to determine the acceptability of SMS interventions among participants in a randomized controlled trial evaluating the efficacy of SMS reminders to improve visit adherence in Gaborone Botswana. The object was to establish whether using SMS reminders was acceptable to patients on ART. The analysis is notable for its implications for the implementation of SMS-based adherence interventions across southern Africa. First it demonstrates that SMS reminders used to remind patients to attend clinic visits and pick up HIV medications are acceptable to patients. Second the data supports the hypothesis that inadvertent HIV status disclosure is an important perceived obstacle to the use of SMS technology in southern Africa. Third the study demonstrates that patients did not want to receive SMS reminders for all areas of their HIV care. [excerpt]

Diabetes mellitus in HIV-infected patients receiving antiretroviral therapy

BACKGROUND There is little in the literature on HIV and diabetes mellitus (DM) in sub-Saharan Africa. OBJECTIVE To assess the characteristics of HIV and DM in patients receiving antiretroviral therapy (ART) in Botswana. METHODS A retrospective case-control study was conducted at 4 sites. Each HIV-infected patient with DM (n=48) was matched with 2 HIV-infected controls (n=108) by age (±2 years) and sex. Primary analysis was conditional logistic regression to estimate univariate odds and 95% confidence intervals (CIs) for each characteristic. RESULTS There was no significant association between co-morbid diseases, tuberculosis, hypertension or cancer and risk of diabetes. DM patients were more likely to have higher pre-ART weight (odds ratio (OR) 1.09; 95% CI 1.04 - 1.14). HIV-infected adults >70 kg were significantly more likely to have DM (OR 12.30; 95% CI 1.40 - 107.98). Participants receiving efavirenz (OR 4.58; 95% CI 1.44 - 14.57) or protease inhibitor therapy (OR 20.7; 95% CI 1.79 - 240.02) were more likely to have DM. Neither mean pre-ART CD4 cell count (OR 1.0; 95% CI 0.99 - 1.01) nor pre-ART viral load >100 000 copies/ml (OR 0.71; 95% CI 0.21 - 2.43) were associated with a significant risk of diabetes. CONCLUSIONS These findings suggest a complex interrelation among traditional host factors and treatment-related metabolic changes in the pathogenesis of DM inpatients receiving ART. Notably, pre-ART weight, particularly if >70 kg, is associated with the diagnosis of diabetes in HIV-infected patients in Botswana.

Addressing the challenge of the emerging NCD epidemic: lessons learned from Botswana’s response to the HIV epidemic

Botswana has the second highest prevalence of human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS) in the world, and yet it has built one of Africas most progressive and comprehensive HIV programs. While public health infrastructure has responded remarkably to the HIV epidemic, the prevalence of non-communicable diseases (NCDs), particularly diabetes mellitus and cardiovascular disease, in both HIV-infected and non-infected individuals, is increasing rapidly. Applying lessons learned from the scale-up of HIV/AIDS services may help with the implementation of an effective response to the challenges of the emerging NCD epidemic. We suggest that a successful response should include integrated service delivery, capacity building to provide disease-specific care, and strong partnerships to mobilize communities.

Higher CD163 levels are associated with insulin resistance in hepatitis C virus-infected and HIV-infected adults.

Objectives: HIV/hepatitis C virus (HCV) coinfection is associated with insulin resistance, but the mechanism is unclear. We hypothesized that intestinal epithelial damage and the consequent monocyte/macrophage activation and inflammation explain this perturbation. Design: Cross-sectional study of 519 adults (220 HIV+/HCV−; 64 HIV−/HCV+; 89 HIV+/HCV+; 146 HIV−/HCV−). Methods: We used multivariable linear regression to evaluate associations of HIV and HCV with the homeostasis model assessment of insulin resistance (HOMA-IR) and if intestinal fatty (FA) acid binding protein (I-FABP, a marker of gut epithelial integrity), soluble CD14 (sCD14) and soluble CD163 (sCD163) (markers of monocyte/macrophage activation), and IL-6 (an inflammatory cytokine) mediated this association. Results: HIV+/HCV+ and HIV−/HCV+ had greater demographic-adjusted HOMA-IR [mean (95% confidence interval (CI)): 1.96 (1.51, 2.54) and 1.65 (1.22, 2.24)] than HIV+/HCV− and HIV−/HCV−[1.41 (1.18, 1.67) and 1.44 (1.17, 1.75), respectively]. After additional adjustment for lifestyle and metabolic factors, HIV+/HCV+ remained associated with 36% (95% CI: 4, 80%) greater HOMA-IR relative to HIV−/HCV−, whereas HIV−/HCV+ and HIV+/HCV− had smaller differences. Adjustment for sCD163 substantially attenuated the difference between HIV+/HCV+ and HIV−/HCV−; adjustment for I-FABP, sCD14, and IL-6 had little effect. Higher sCD163 was independently associated with 19% (95% CI: 7, 33%), 26% (95% CI: 15, 39%), 25% (95% CI: 14, 37%), and 23% (95% CI: 11, 36%) greater HOMA-IR in HIV+/HCV+, HIV−/HCV+, HIV+/HCV−, and HIV−/HCV− (all estimates per doubling of sCD163). I-FABP, sCD14, and IL-6 were not associated with HOMA-IR. Conclusion: HIV/HCV coinfection is associated with greater HOMA-IR, even after controlling for demographic, lifestyle, and metabolic factors. sCD163, which appears independent of intestinal epithelial damage and inflammation, partly explains this association. Our findings that the association of sCD163 with HOMA-IR occurred even in the absence of HIV and HCV, indicate that viral and nonviral factors affect sCD163 levels. Its role in insulin resistance needs elucidation.