Influence of hepatitis B virus co-infection on virological and immunological response to antiretroviral treatment among HIV patients attending comprehensive care clinics in Makueni County, Kenya.

INTRODUCTION: the effect of hepatitis B virus (HBV) infection on the natural history of human immunodeficiency virus (HIV) disease remains uncertain. Therefore, this study was conducted to determine the association of HBV co-infections with CD4 count and viral load levels in response to antiretroviral treatment among HIV patients attending comprehensive care clinics in Makueni County (Kenya). METHODS: this was a prospective case-control study among patients seeking HIV services in three hospitals of Makueni County (Kenya). Newly diagnosed HIV mono-infected patients (controls) and HIV/HBV co-infected (cases), 18 years and above who had not started antiretrovirals (ARVs) participated. A total of 258 patients gave informed consent and participated. HIV mono-infected (controls) produced 129 while HIV/HBV (cases) gave 129 participants. P-values ≤ 0.05 were considered significant. RESULTS: the majority (164, 63%) of the study participants were females for both arms of the study. The mean age of the participants was 31±0.402 years and majority of them were between the age of 26-30years old. At the beginning and end of the study the mean viral load for HIV/HBV co-infected individuals was (30169 and 1731) copies/ml while that of CD4 count was (327 and 459) cells/ul, and that of HIV mono-infected was (21860 and 1689) copies/ml and CD4 count of (421 and 437) cells/ul respectively. After enrolling them into antiretroviral therapy (ART) treatment and after six months of follow-up there was significant drop in viral load and significant increase in CD4 count for both groups at p<0.001 using logistic regression. CONCLUSION: HIV patients co-infected with hepatitis B virus had high viral load and low CD4 count compared to HIV monoinfected patients however with introduction of ARVs there was improvement in both groups with the highest noticed among the HIV/HBV co-infected patients.

Patient costs of diabetes mellitus care in public health care facilities in Kenya.

OBJECTIVE: To estimate the direct and indirect costs of diabetes mellitus care at five public health facilities in Kenya. METHODS: We conducted a cross-sectional study in two counties where diabetes patients aged 18 years and above were interviewed. Data on care-seeking costs were obtained from 163 patients seeking diabetes care at five public facilities using the cost-of-illness approach. Medicines and user charges were classified as direct health care costs while expenses on transport, food, and accommodation were classified as direct non-health care costs. Productivity losses due to diabetes were classified as indirect costs. We computed annual direct and indirect costs borne by these patients. RESULTS: More than half (57.7%) of sampled patients had hypertension comorbidity. Overall, the mean annual direct patient cost was KES 53 907 (95% CI, 43 625.4-64 188.6) (US$ 528.5 [95% CI, 427.7-629.3]). Medicines accounted for 52.4%, transport 22.6%, user charges 17.5%, and food 7.5% of total direct costs. Overall mean annual indirect cost was KES 23 174 (95% CI, 20 910-25 438.8) (US$ 227.2 [95% CI, 205-249.4]). Patients reporting hypertension comorbidity incurred higher costs compared with diabetes-only patients. The incidence of catastrophic costs was 63.1% (95% CI, 55.7-70.7) and increased to 75.4% (95% CI, 68.3-82.1) when transport costs were included. CONCLUSION: There are substantial direct and indirect costs borne by diabetic patients in seeking care from public facilities in Kenya. High incidence of catastrophic costs suggests diabetes services are unaffordable to majority of diabetic patients and illustrate the urgent need to improve financial risk protection to ensure access to care.

Prospective International Study of Incidence and Predictors of Immune Reconstitution Inflammatory Syndrome and Death in People Living With Human Immunodeficiency Virus and Severe Lymphopenia.

BACKGROUND: Patients living with human immunodeficiency virus (PLWH) with low CD4 counts are at high risk for immune reconstitution inflammatory syndrome (IRIS) and death at antiretroviral therapy (ART) initiation. METHODS: We investigated the clinical impact of IRIS in PLWH and CD4 counts <100 cells/µL starting ART in an international, prospective study in the United States, Thailand, and Kenya. An independent review committee adjudicated IRIS events. We assessed associations between baseline biomarkers, IRIS, immune recovery at week 48, and death by week 48 with Cox models. RESULTS: We enrolled 506 participants (39.3% were women). Median age was 37 years, and CD4 count was 29 cells/µL. Within 6 months of ART, 97 (19.2%) participants developed IRIS and 31 (6.5%) died. Participants with lower hemoglobin at baseline were at higher IRIS risk (hazard ratio [HR], 1.2; P = .004). IRIS was independently associated with increased risk of death after adjustment for known risk factors (HR, 3.2; P = .031). Being female (P = .004) and having a lower body mass index (BMI; P = .003), higher white blood cell count (P = .005), and higher D-dimer levels (P = .044) were also significantly associated with increased risk of death. Decision-tree analysis identified hemoglobin <8.5 g/dL as predictive of IRIS and C-reactive protein (CRP) >106 µg/mL and BMI <15.6 kg/m2 as predictive of death. CONCLUSIONS: For PLWH with severe immunosuppression initiating ART, baseline low BMI and hemoglobin and high CRP and D-dimer levels may be clinically useful predictors of IRIS and death risk.

Diagnostic Accuracy of Unattended Automated Office Blood Pressure Measurement in Screening for Hypertension in Kenya.

Despite increasing adoption of unattended automated office blood pressure (uAOBP) measurement for determining clinic blood pressure (BP), its diagnostic performance in screening for hypertension in low-income settings has not been determined. We determined the validity of uAOBP in screening for hypertension, using 24-hour ambulatory BP monitoring as the reference standard. We studied a random population sample of 982 Kenyan adults; mean age, 42 years; 60% women; 2% with diabetes mellitus; none taking antihypertensive medications. We calculated sensitivity using 3 different screen positivity cutoffs (≥130/80, ≥135/85, and ≥140/90 mm Hg) and other measures of validity/agreement. Mean 24-hour ambulatory BP monitoring systolic BP was similar to mean uAOBP systolic BP (mean difference, 0.6 mm Hg; 95% CI, -0.6 to 1.9), but the 95% limits of agreement were wide (-39 to 40 mm Hg). Overall discriminatory accuracy of uAOBP was the same (area under receiver operating characteristic curves, 0.66-0.68; 95% CI range, 0.64-0.71) irrespective of uAOBP cutoffs used. Sensitivity of uAOBP displayed an inverse association (P<0.001) with the cutoff selected, progressively decreasing from 67% (95% CI, 62-72) when using a cutoff of ≥130/80 mm Hg to 55% (95% CI, 49-60) at ≥135/85 mm Hg to 44% (95% CI, 39-49) at ≥140/90 mm Hg. Diagnostic performance was significantly better (P<0.001) in overweight and obese individuals (body mass index, >25 kg/m2). No differences in results were present in other subanalyses. uAOBP misclassifies significant proportions of individuals undergoing screening for hypertension in Kenya. Additional studies on how to improve screening strategies in this setting are needed.

Khat use and psychotic symptoms in a rural Khat growing population in Kenya: a household survey.

BACKGROUND: Khat is an amphetamine like psychostimulant chewed by over 10 million people globally. Khat use is thought to increase the risk of psychosis among its chewers. The evidence around this however remains inconclusive stemming from the scanty number of studies in this area and small study sample sizes. We undertook a large household survey to determine the association between psychotic symptoms and khat chewing in a rural khat growing and chewing population in Kenya. METHODS: For this cross-sectional household survey, we randomly selected 831 participants aged 10 years and above residing in the Eastern region of Kenya. We used the psychosis screening questionnaire (PSQ) to collect information on psychotic symptoms and a researcher designed sociodemographic and clinical questionnaire to collect information on its risk factors. We used descriptive analysis to describe the burden of khat chewing and other substance use as well as rates and types of psychotic symptoms. Using a univariate and multivariate analyses with 95% confidence interval, we estimated the association between khat chewing and specific psychotic symptoms. RESULTS: The prevalence of current khat chewing in the region was at 36.8% (n = 306) with a male gender predominance (54.8%). At least one psychotic symptom was reported by 16.8% (n = 168) of the study population. Interestingly, psychotic symptoms in general were significantly prevalent in women (19.5%) compared to men (13.6%) (p = 0.023). Khat chewing was significantly associated with reported strange experiences (p = 0.024) and hallucinations (p = 0.0017), the two predominantly reported psychotic symptoms. In multivariate analysis controlling for age, gender, alcohol use and cigarette smoking, there was a positive association of strange experiences (OR, 2.45; 95%CI, 1.13-5.34) and hallucination (OR, 2.08; 95% C.I, 1.06-4.08) with khat chewing. Of note was the high concurrent polysubstance use among khat chewers specifically alcohol use (78.4%) and cigarette smoking (64.5%). CONCLUSIONS: Psychotic symptoms were significantly elevated in khat users in this population. Future prospective studies examining dose effect and age of first use may establish causality.

Patient costs of hypertension care in public health care facilities in Kenya.

BACKGROUND: Hypertension in low- and middle-income countries, including Kenya, is of economic importance due to its increasing prevalence and its potential to present an economic burden to households. In this study, we examined the patient costs associated with obtaining care for hypertension in public health care facilities in Kenya. METHODS: We conducted a cross-sectional study among adult respondents above 18 years of age, with at least 6 months of treatment in two counties. A total of 212 patients seeking hypertension care at five public facilities were interviewed, and information on care seeking and the associated costs was obtained. We computed both annual direct and indirect costs borne by these patients. RESULTS: Overall, the mean annual direct cost to patients was US$ 304.8 (95% CI, 235.7-374.0). Medicines (mean annual cost, US$ 168.9; 95% CI, 132.5-205.4), transport (mean annual cost, US$ 126.7; 95% CI, 77.6-175.9), and user charges (mean annual cost, US$ 57.7; 95% CI, 43.7-71.6) were the highest direct cost categories. Overall mean annual indirect cost was US$ 171.7 (95% CI, 152.8-190.5). The incidence of catastrophic health care costs was 43.3% (95% CI, 36.8-50.2) and increased to 59.0% (95% CI, 52.2-65.4) when transport costs were included. CONCLUSIONS: Hypertensive patients incur substantial direct and indirect costs. High rates of catastrophic costs illustrate the urgency of improving financial risk protection for these patients and strengthening primary care to ensure affordability of hypertension care.

Risk factors for early mortality on antiretroviral therapy in advanced HIV-infected adults.

BACKGROUND: Many HIV-infected individuals present with advanced HIV disease. These patients are at high risk of death after antiretroviral therapy (ART) initiation, but risk factors for death in these patients are unclear. METHODS: We used data from a multisite randomized trial comparing empiric vs. preventive tuberculosis therapy in HIV-infected adults initiating ART with CD4 T-cell counts less than 50 cells/µl to evaluate risk factors for death within 48 weeks after ART initiation. Cox proportional hazards models were fit to evaluate characteristics present at baseline and at 4 weeks after ART initiation, including the week 4 CD4 T-cell response and new opportunistic infections. RESULTS: Of 850 enrolled, the median pre-ART CD4 T-cell count was 18 cells/µl and 67 (7.9%) died. Baseline risk factors for death included lymphadenopathy, lower CD4 T-cell count, lower serum albumin, high white blood cell count, elevated neutrophil percentage, and lower hemoglobin. Among 746 participants with data at week 4, the median changes in CD4 T-cell count and viral load for those who died (n = 43) vs. survived were 26 vs. 56 cells/µl and -2.7 vs. -2.7 log10 copies/ml, respectively. Each 20 cell/µl lower change in week 4 CD4 T-cell count was associated with a 20% increased risk of post week-4 mortality (adjusted hazard ratio 1.20, 1.01-1.42, P = .038). CONCLUSION: Evidence of active infection and suboptimal immunologic response during the first month of ART are associated with death in the first year after ART initiation in those with advanced HIV disease taking tuberculosis preventive therapy. Strategies to reduce early mortality in this population warrant further investigation.

Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open-label randomised controlled trial.

BACKGROUND: Mortality within the first 6 months after initiating antiretroviral therapy is common in resource-limited settings and is often due to tuberculosis in patients with advanced HIV disease. Isoniazid preventive therapy is recommended in HIV-positive adults, but subclinical tuberculosis can be difficult to diagnose. We aimed to assess whether empirical tuberculosis treatment would reduce early mortality compared with isoniazid preventive therapy in high-burden settings. METHODS: We did a multicountry open-label randomised clinical trial comparing empirical tuberculosis therapy with isoniazid preventive therapy in HIV-positive outpatients initiating antiretroviral therapy with CD4 cell counts of less than 50 cells per µL. Participants were recruited from 18 outpatient research clinics in ten countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda). Individuals were screened for tuberculosis using a symptom screen, locally available diagnostics, and the GeneXpert MTB/RIF assay when available before inclusion. Study candidates with confirmed or suspected tuberculosis were excluded. Inclusion criteria were liver function tests 2·5 times the upper limit of normal or less, a creatinine clearance of at least 30 mL/min, and a Karnofsky score of at least 30. Participants were randomly assigned (1:1) to either the empirical group (antiretroviral therapy and empirical tuberculosis therapy) or the isoniazid preventive therapy group (antiretroviral therapy and isoniazid preventive therapy). The primary endpoint was survival (death or unknown status) at 24 weeks after randomisation assessed in the intention-to-treat population. Kaplan-Meier estimates of the primary endpoint across groups were compared by the z-test. All participants were included in the safety analysis of antiretroviral therapy and tuberculosis treatment. This trial is registered with ClinicalTrials.gov, number NCT01380080. FINDINGS: Between Oct 31, 2011, and June 9, 2014, we enrolled 850 participants. Of these, we randomly assigned 424 to receive empirical tuberculosis therapy and 426 to the isoniazid preventive therapy group. The median CD4 cell count at baseline was 18 cells per µL (IQR 9-32). At week 24, 22 (5%) participants from each group died or were of unknown status (95% CI 3·5-7·8) for empirical group and for isoniazid preventive therapy (95% CI 3·4-7·8); absolute risk difference of -0·06% (95% CI -3·05 to 2·94). Grade 3 or 4 signs or symptoms occurred in 50 (12%) participants in the empirical group and 46 (11%) participants in the isoniazid preventive therapy group. Grade 3 or 4 laboratory abnormalities occurred in 99 (23%) participants in the empirical group and 97 (23%) participants in the isoniazid preventive therapy group. INTERPRETATION: Empirical tuberculosis therapy did not reduce mortality at 24 weeks compared with isoniazid preventive therapy in outpatient adults with advanced HIV disease initiating antiretroviral therapy. The low mortality rate of the trial supports implementation of systematic tuberculosis screening and isoniazid preventive therapy in outpatients with advanced HIV disease. FUNDING: National Institutes of Allergy and Infectious Diseases through the AIDS Clinical Trials Group.

Geographical variation in the response of visceral leishmaniasis to paromomycin in East Africa: a multicentre, open-label, randomized trial.

BACKGROUND: Visceral leishmaniasis (VL) is a major health problem in developing countries. The untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. Improved treatment options are needed. Paromomycin was shown to be an efficacious first-line treatment with low toxicity in India. METHODS: This was a 3-arm multicentre, open-label, randomized, controlled clinical trial to compare three treatment regimens for VL in East Africa: paromomycin sulphate (PM) at 15 mg/kg/day for 21 days versus sodium stibogluconate (SSG) at 20 mg/kg/day for 30 days; and the combination of both dose regimens for 17 days. The primary efficacy endpoint was cure based on parasite-free tissue aspirates taken 6 months after treatment. FINDINGS: Overall, 135 patients per arm were enrolled at five centres in Sudan (2 sites), Kenya (1) and Ethiopia (2), when the PM arm had to be discontinued due to poor efficacy. The trial has continued with the higher dose of PM as well as the combination of PM and SSG arms. These results will be reported later. Baseline patient characteristics were similar among treatment arms. The overall cure with PM was significantly inferior to that with SSG (63.8% versus 92.2%; difference 28.5%, 95%CI 18.8% to 38.8%, p<0.001). The efficacy of PM varied among centres and was significantly lower in Sudan (14.3% and 46.7%) than in Kenya (80.0%) and Ethiopia (75.0% and 96.6%). No major safety issues with PM were identified. CONCLUSION: The efficacy of PM at 15 mg/kg/day for 21 days was inadequate, particularly in Sudan. The efficacy of higher doses and the combination treatment warrant further studies.