Maxwell O. Akanbi

Genetic Determinants of Drug-Resistant Tuberculosis among HIV-Infected Patients in Nigeria

ABSTRACT Tuberculosis (TB) is the most common opportunistic infection in human immunodeficiency virus (HIV)-infected patients and the emergence of drug-resistant tuberculosis (DR-TB) is a growing problem in resource-limited settings. Adequate infrastructure for testing drug sensitivity and sufficient evidence of first-line resistance are currently unavailable in Nigeria. We collected sputum samples from HIV-infected patients enrolled in the Harvard PEPFAR/APIN Plus program over 12 months at two PEPFAR antiretroviral therapy (ART) clinics in the southwest and north central regions in Nigeria. Smear-positive sputum samples were submitted for GenoType MTBDRplus testing (n = 415); mutations were confirmed through sequencing. Our results show high rates of DR-TB in Nigerian HIV-infected individuals (7.0% for rifampin [RIF] and 9.3% for RIF or isoniazid [INH]). Total RIF resistance indicative of MDR-TB in treatment-naive patients was 5.52%, far exceeding the World Health Organization predictions (0 to 4.3%). RIF resistance was found in 6/213 (2.8%) cases, INH resistance was found in 3/215 (1.4%) cases, and MDR-TB was found in 8/223 (3.6%) cases. We found significantly different amounts of DR-TB by location (18.18% in the south of the country versus 3.91% in the north central region [P < 0.01]). Furthermore, RIF resistance was genetically distinct, suggesting possible location-specific strains are responsible for the transmission of drug resistance (P < 0.04). Finally, GenoType MTBDRplus correctly identified the drug-resistant samples compared to sequencing in 96.8% of cases. We found that total DR-TB in HIV-infection is high and that transmission of drug-resistant TB in HIV-infected patients in Nigeria is higher than predicted.

High-risk of obstructive sleep apnea and excessive daytime sleepiness among commercial intra-city drivers in Lagos metropolis

Background: The burden of obstructive sleep apnea among commercial drivers in Nigeria is not known. Aim: To assess the prevalence of high risk of obstructive sleep apnea (OSA) and excessive daytime sleepiness (EDS) among intra-city commercial drivers. Setting and Design: A descriptive cross-sectional study in three major motor parks in Lagos metropolis. Materials and Methods: Demographic, anthropometric and historical data was obtained. The risk of OSA and EDS was assessed using the STOP BANG questionnaire and the Epworth Sleepiness Scale, respectively. Statistical Analysis: The relationship between the OSA risk, EDS risk and past road traffic accident (RTA) was explored using the Pearsons chi square. Independent determinants of OSA risk, EDS risk and past RTA, respectively, were assessed by multiple logistic regression models. Result: Five hundred male commercial drivers (mean age (years) ±SD = 42.36 ± 11.17 and mean BMI (kg/m2) ±SD = 25.68 ± 3.79) were recruited. OSA risk was high in 244 (48.8%) drivers and 72 (14.4%) had EDS. There was a positive relationship between OSA risk and the risk of EDS (Pearsons X2 = 28.2, P < 0.001). Sixty-one (12.2%) drivers had a past history of RTA but there was no significant relationship between a past RTA and either OSA risk (X2 = 2.05, P = 0.15) or EDS risk (X2 = 2.7, P = 0.1), respectively. Abdominal adiposity, regular alcohol use and EDS were independent determinants of OSA risk while the use of cannabis and OSA risk were independent determinants of EDS. No independent risk factor for past RTA was identified. Conclusion: A significant proportion of commercial drivers in Lagos metropolis are at high risk of OSA and EDS.

Awareness and knowledge of human immunodeficiency virus post exposure prophylaxis among Nigerian Family Physicians

Background: To determine the level of awareness and knowledge of HIV postexposure prophylaxis (HIV PEP) and determinants of adequate knowledge among Family Physicians in Nigeria. Materials and Methods: This was a cross-sectional questionnaire-based survey conducted among 175 Family Physicians at two national conferences. Results: Majority (97.7%) of the respondents was aware of the concept of HIV PEP and 99.4% believed it was effective in preventing HIV transmission. Over two third of our respondents had been exposed to NSI; however, less than 25% of those exposed received PEP. There was high level of knowledge of the various high-risk body fluids as well as types of high-risk exposures. 93.9% of our respondents knew that HIV PEP should commence within 1 h of exposure, 83.3% knew the correct duration of HIV PEP, but only 57.0% knew the ideal PEP regimen for high-risk exposures. The total mean score for our respondents was 17.8±2.9 with 79.4% having an adequate score. Being a junior doctor and male sex were associated with adequate knowledge. Conclusion: This study shows that despite high levels of awareness and knowledge of HIV PEP, access to its use among family physicians in Nigeria is still sub-optimal.

Incidence and predictors of adverse drug events in an African cohort of HIV-infected adults treated with efavirenz

INTRODUCTION Adverse drug reactions associated with efavirenz (EFV) therapy are poorly described beyond the first year of treatment. We aimed to describe the incidence and predictors of EFV-related adverse drug reactions (ADRs) in a cohort of adult Nigerian HIV-infected patients on antiretroviral therapy (ART). METHODS This retrospective cohort study utilized clinical data of HIV-1 infected adults (aged ≥15 years), commenced on efavirenz containing-regimen between January 2004 and December 2011. The time-dependent occurrence of clinical adverse events as defined by the World Health Organization was analyzed by Cox regression analysis. RESULTS A total of 2920 patients with baseline median (IQR) age of 39 (33-46) years, largely made up of men (78%) were included in the study. During 8834 person-years of follow up, 358 adverse drug events were reported; the incidence rate was 40.3 ADRs per 1000 person-years of treatment. Lipodystrophy and neuropsychiatric disorders were the most common ADRs with incidences of 63 and 30 per 1000 patients respectively. About one-third of the neuropsychiatric adverse events were within 12 months of commencement of ART. The risk of neuropsychiatric ADRs was independently predicted for women [adjusted hazard ratio (aHR) 9.05; 95% CI: 5.18-15.82], those aged <40 years (aHR 2.59; 95% CI: 1.50-4.45), advanced HIV disease (WHO stage 3 or 4) [aHR 2.26; 95% CI: 1.37-3.72], and zidovudine [aHR 2.21; 95% CI: 1.27-3.83] or stavudine [aHR 4.22; 95% CI: 1.99-8.92] containing regimen compared to tenofovir. CONCLUSION Neuropsychiatric adverse drug events associated with efavirenz-based ART had both early and late onset in our clinical cohort of patients on chronic EFV therapy. Continuous neuropsychiatric assessment for improved detection and management of neuropsychiatric ADRs is recommended in resource-limited settings where the use of efavirenz-based regimens has been scaled up.

HIV associated chronic obstructive pulmonary disease in Nigeria.

OBJECTIVE To determine the prevalence and risk factors for chronic obstructive pulmonary disease (COPD) among HIV-infected adults in Nigeria. DESIGN Cross-sectional study. METHODS HIV-infected adults aged ≥ 30 years with no acute ailments accessing care at the antiretroviral therapy clinic of Jos University Teaching Hospital were enrolled consecutively. Participants were interviewed to obtain pertinent demographic and clinical information, including exposure to risk factors for COPD. Post-bronchodilator spirometry was carried out. HIV related information was retrieved from the clinic medical records. COPD case-definition was based on the Global Initiative for Obstructive Lung Disease (GOLD) criteria using post-bronchodilator FEV1/FVC <0.7. COPD prevalence was also calculated using the lower limit of normal for FEV1/FVC criteria (LLN) from the European Respiratory Society normative equation. Factors associated with COPD were determined using logistic regression models. RESULTS Study population comprised 356 HIV infected adults with mean age of 44.5 (standard deviation, 7.1) years and 59% were female. The mean time elapsed since HIV diagnosis was 7.0 (SD, 2.6) years and 97.5% of the respondents were on stable ART with virologic suppression present in 67.2%. Prevalence of COPD were 15.4% (95% confidence interval [CI] 11.7-19.2), 12.07% (95% CI 8.67-15.48), 22.19% (95% CI 18.16-26.83) using GOLD, ERS LLN and GLI LLN diagnostic criteria respectively. In multivariate analyses adjusting for gender, exposure to cigarette smoke or biomass, history of pulmonary tuberculosis, use of antiretroviral therapy, current CD4 T-cell count and HIV RNA, only age > 50 years was independently associated with COPD with OR 3.4; 95% CI 1.42-8.17 when compared to ages 30-40 years. CONCLUSION HIV-associated COPD is common in our population of HIV patients.

Factors Associated With Pulmonary Tuberculosis-HIV Co-Infection in Treatment-Naive Adults in Jos, North Central Nigeria

Background: Co-infection with tuberculosis and human immunodeficiency virus (TB-HIV) remains a major global health problem, with about 1.1 million new cases of TB in HIV-positive persons reported in 2011; 79% of the reported cases were amongst patients living in Africa. Advanced immune suppression remains the most important risk factor for tuberculosis in those with HIV, but epidemiological and clinical factors have also been identified. We sought to determine the prevalence and factors associated with pulmonary tuberculosis (PTB) in antiretroviral therapy (ART)- naive HIV-infected patients seeking HIV care services at a tertiary health facility in North Central Nigeria. Methods: We compared clinical and laboratory data for 218 HIV-1 positive adults with and without a diagnosis of pulmonary tuberculosis. Results from univariate analyses informed the selection of predictors to conduct multivariate analysis to determine which factors were associated with presence of PTB-HIV co-infection. Results: The prevalence of PTB-HIV co-infection in the evaluated cohort was 9.6%. Lower CD4+ cell count and the presence of oropharyngeal candidiasis were independently associated with PTB-HIV co-infection. CD4+ cell count was strongly associated with PTB-HIV co-infection (p=0.002) with the odds of co-infection reduced by 85% in those with a CD4+ cell count >100 cells/mm3 compared to those with <100 cells/ mm3. There was a strong association between oropharyngeal candidiasis and PTB-HIV co-infection, where the odds of co-infection are about 4.5 times higher in those with oropharyngeal candidiasis than those without candidiasis (p=0.008). Conclusion: PTB was prevalent among HIV patients seeking care in our setting. Severe immune suppression and oropharyngeal candidiasis were associated with PTB-HIV co-infection in our patients at presentation. Potential implications for severe immune suppression and advanced HIV disease are a poor clinical outcome and further spread of PTB. Strategies to encourage the early diagnosis of both HIV and TB should be considered

Combination Nucleoside/Nucleotide Reverse Transcriptase Inhibitors for Treatment of HIV Infection

Introduction: The combination of two nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) and a third agent from another antiretroviral class is currently recommended for initial antiretroviral therapy. In general, N(t)RTIs remain relevant in subsequent regimens. There are currently six nucleoside reverse transcriptase inhibitors and one nucleotide reverse transcriptase inhibitor drug entities available, and several formulations that include two or more N(t)RTIs in a fixed-dose combination. These entities have heterogeneous pharmacological and clinical properties. Accordingly, toxicity, pill burden, dosing frequency, potential drug–drug interaction, preexisting antiretroviral drug resistance and comorbid conditions should be considered when constructing a regimen. This approach is critical in order to optimize virologic efficacy and clinical outcomes. Areas covered: This article reviews N(t)RTI combinations used in the treatment of HIV-infected adults. The pharmacological properties of each N(t)RTI, and the clinical trials that have influenced treatment guidelines are discussed. Expert opinion: It is likely that N(t)RTIs will continue to dominate the global landscape of HIV treatment and prevention, despite emerging interest in N(t)RTI-free combination therapy. Clinical domains where only few alternatives to N(t)RTIs exist include treatment of HIV/HBV coinfection and HIV-2. There is a need for novel N(t)RTIs with enhanced safety and resistance profiles compared with current N(t)RTIs.

Specialist physician knowledge of chronic kidney disease: A comparison of internists and family physicians in West Africa

Abstract Background Postgraduate training is aimed at equipping the trainee with the necessary skills to practise as an expert. Non-nephrology specialist physicians render the bulk of pre-end-stage renal disease care for patients with chronic kidney disease (CKD). We sought to ascertain the knowledge of CKD amongst non-nephrology specialist physicians who serve as trainers and examiners for a training, accrediting and certifying body in postgraduate medicine in West Africa. We also compared the knowledge of family physicians and non-nephrology internists. Methods Self-administered questionnaires were distributed to non-nephrology specialist physicians who serve as examiners for the West African College of Physicians. Results Only 19 (27.5%) of the respondents were aware of the Kidney Disease Outcomes Quality Initiatives guidelines for CKD management. Twenty five (36.2%) of the respondents had adequate knowledge of CKD. There was no significant difference in the proportion of family physicians and non-nephrology internists who had adequate knowledge of CKD (27.3% vs. 40.4% respectively; p = 0.28). Hypertension and diabetes mellitus were identified by all of the physicians as risk factors for CKD. Non-nephrology internists more frequently identified systemic lupus erythematosus as a risk factor for CKD, urinalysis with microscopy as a laboratory test for CKD evaluation, and bone disease as a complication of CKD than family physicians. Conclusion There is a lack of adequate CKD knowledge amongst non-nephrology specialist physicians, since many of them are unaware of the CKD management guidelines. Educational efforts are needed to improve the knowledge of CKD amongst non-nephrology specialist physicians. Guidelines on CKD need to be widely disseminated amongst these physicians.

Sexual functioning and health-related quality of life in men

Background: Although erectile dysfunction (ED) is common, little is known about the impact of ED on the quality of life (QoL) among African men. Materials and Methods: We used the International Index of Erectile Function (IIEF) to evaluate ED and the WONCA charts to assess QoL among employees of a university. Results: A total of 508 men with a mean age of 43 ± 10 years were studied. IIEF5 scores of <22 were present in 406 participants (77.9%). Mild ED, mild-to-moderate ED, moderate ED, and severe ED were present in 34.6%, 26.6%, 10.4%, and 5.7%, respectively. Systolic and diastolic blood pressure were significantly lower in those with ED. Marital status, alcohol, cigarette, physical inactivity, obesity, hypertension, diabetes mellitus, and antihypertensive drug use were not associated with ED. ED was associated with poor QoL in the domains of social activities (odds ratio [OR] = 4.35; 95% confidence interval [CI]: 1.01–18.7), and overall health (OR = 2.27; 95% CI: 1.07–4.82). However, there was no association of ED with poor QoL in the domains of physical fitness (OR = 1.46; 95% CI: 0.82–2.59), feelings (OR = 1.43; 95% CI: 0.75–2.72), daily activities (OR = 4.72; 95% CI: 0.61–36.4), and change in health (OR = 1.75; 95% CI: 0.58–5.26). Conclusion: ED negatively impacts QoL in men.

Obesity and obstructive sleep apnea risk among Nigerians

Background: The contribution of obesity to obstructive sleep apnea (OSA) is poorly described in Nigeria. We aimed to compare OSA risk between obese and nonobese adults in urban Nigeria. Materials and Methods: An analytic cross-sectional study was conducted. Participants were interviewed using the World Health Organization Non-Communicable Disease questionnaire. OSA risk assessment was performed using the STOP-BANG questionnaire. A total score of ≥3 on the STOP-BANG questionnaire indicated OSA risk, whereas a score ≥5 indicated high OSA risk. Obesity was defined as body mass index (BMI) >30 kg/m2. Relationship between obesity and OSA was tested using chi-square and logistic regression models used to control for confounding factors. Results: There were 744 respondents, with a mean age of 44 (standard deviation 10) years. A total of 206 [27.7%, 95% confidence interval (CI) 24.46–30.9] respondents were obese (BMI ≥30 kg/m2). A total of 307 (41.3%, 95% CI 37.7–44.9) respondents scored ≥3 on the STOP-BANG questionnaire, whereas 37 (4.9%, 95% CI 3.6–6.7) scored ≥5. More number of obese than nonobese [57.8% (119/206) versus 34.9% (188/538)] respondents met the criteria for OSA risk (P < 0.001). Similarly, more obese persons [10.3% (21/206)] met the criteria for high-risk OSA compared to the nonobese [3% (16/538)]; P < 0.001. In logistic regression models adjusted for cigarette smoking and alcohol consumption, the odds for OSA risk was 15.76 (95% CI 7.44–33.9) in persons with BMI >35 kg/m2 compared to those with a BMI range of 18.5–24.99. Conclusion: Obesity and OSA may be more prevalent in Nigeria than previously predicted. Obesity independently increased OSA risk in this population.