Proximal tubular renal dysfunction among HIV infected patients on Tenofovir versus Tenofovir sparing regimen in western Kenya.

INTRODUCTION: Tenofovir Disoproxil Fumarate (TDF) is the most widely used Anti-Retroviral Therapy (ART) drug due to its potency, safety profile and World Health Organization (WHO) recommendation. TDF causes proximal tubular renal dysfunction (PTRD) leading to Fanconi syndrome, acute kidney injury and chronic kidney disease. Modest rates (2-4%) of TDF related toxicity based on estimated Glomerular Filtration Rate (GFR) have been described, while TDF-induced PTRD has been reported to be 22%. TDF toxicity is more likely among African patients, it is reversible and TDF may be renal dosed in patients with dysfunction. The objective of this study was to assess proximal tubular renal dysfunction, global renal function, and their determinants among patients on TDF versus TDF-sparing regimen. METHODS: This was a cross-sectional study among people living with HIV/AIDS (PLWHA) attending the Academic Model Providing Access to Healthcare (AMPATH) program. The primary outcome of interest in this study was PTRD while the secondary outcome of interest was estimated GFR. PTRD was defined as any two of beta-2 microglobulin in urine, metabolic acidosis, normoglycemic glucosuria and fractional excretion of phosphate. Student's t-test, chi-square and their non-parametric equivalents were used to test for statistical significance. Univariate and multivariate logistic regression analysis was carried out. RESULTS: A total of 516 participants were included in the final analysis, 261 on TDF while 255 were on TDF-sparing regimens. The mean (SD) age of all participants was 41.5 (12.6) years with majority being female (60.3%). The proportion of PTRD was 10.0% versus 3.1% in the TDF compared to TDF-sparing group (P<0.001). Mean estimated GFR was 112.8 (21.5) vs 109.7 (21.9) ml/min/1.73mm3 (P = 0.20) for the TDF compared to TDF-sparing group. TDF users were more likely to have PTRD compared to non-TDF users, adjusted Odds Ratio (AOR) 3.0, 95% CI 1.12 to 7.75. CONCLUSION: There was significant PTRD in the TDF compared to TDF-sparing group without significant difference in estimated GFR. The clinical significance of these findings may not be clear in the short term.

Estimating kidney function in HIV-infected adults in Kenya: comparison to a direct measure of glomerular filtration rate by iohexol clearance.

BACKGROUND: More than two-thirds of the world's HIV-positive individuals live in sub-Saharan Africa, where genetic susceptibility to kidney disease is high and resources for kidney disease screening and antiretroviral therapy (ART) toxicity monitoring are limited. Equations to estimate glomerular filtration rate (GFR) from serum creatinine were derived in Western populations and may be less accurate in this population. METHODS: We compared results from published GFR estimating equations with a direct measure of GFR by iohexol clearance in 99 HIV-infected, ART-naïve Kenyan adults. Iohexol concentration was measured from dried blood spots on filter paper. The bias ratio (mean of the ratio of estimated to measured GFR) and accuracy (percentage of estimates within 30% of the measured GFR) were calculated. RESULTS: The median age was 35 years, and 60% were women. The majority had asymptomatic HIV, with median CD4+ cell count of 355 cells/mm(3). Median measured GFR was 115 mL/min/1.73 m(2). Overall accuracy was highest for the Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equation. Consistent with a prior report, bias and accuracy were improved by eliminating the coefficient for black race (85% of estimates within 30% of measured GFR). Accuracy of all equations was poor in participants with GFR 60-90 mL/min/1.73 m(2) (<65% of estimates within 30% of measured GFR), although this subgroup was too small to reach definitive conclusions. CONCLUSIONS: Overall accuracy was highest for the CKD-EPI equation. Eliminating the coefficient for race further improved performance. Future studies are needed to determine the most accurate GFR estimate for use in individuals with GFR <90 mL/min/1.73 m(2), in whom accurate estimation of kidney function is important to guide drug dosing. Direct measurement of GFR by iohexol clearance using a filter paper based assay is feasible for research purposes in resource-limited settings, and could be used to develop more accurate GFR estimates in African populations.

Treatment outcomes of a stage 1 cognitive-behavioral trial to reduce alcohol use among human immunodeficiency virus-infected out-patients in western Kenya.

AIMS: Dual epidemics of human immunodeficiency virus (HIV) and alcohol use disorders, and a dearth of professional resources for behavioral treatment in sub-Saharan Africa, suggest the need for development of culturally relevant and feasible interventions. The purpose of this study was to test the preliminary efficacy of a culturally adapted six-session gender-stratified group cognitive-behavioral therapy (CBT) intervention delivered by paraprofessionals to reduce alcohol use among HIV-infected out-patients in Eldoret, Kenya. DESIGN: Randomized clinical trial comparing CBT against a usual care assessment-only control. SETTING: A large HIV out-patient clinic in Eldoret, Kenya, part of the Academic Model for Providing Access to Healthcare collaboration. PARTICIPANTS: Seventy-five HIV-infected out-patients who were antiretroviral (ARV)-initiated or ARV-eligible and who reported hazardous or binge drinking. MEASUREMENTS: Percentage of drinking days (PDD) and mean drinks per drinking days (DDD) measured continuously using the Time line Follow back method. FINDINGS: There were 299 ineligible and 102 eligible out-patients with 12 refusals. Effect sizes of the change in alcohol use since baseline between the two conditions at the 30-day follow-up were large [d=0.95, P=0.0002, mean difference=24.93, 95% confidence interval (CI): 12.43, 37.43 PDD; d=0.76, P=0.002, mean difference=2.88, 95% CI: 1.05, 4.70 DDD]. Randomized participants attended 93% of the six CBT sessions offered. Reported alcohol abstinence at the 90-day follow-up was 69% (CBT) and 38% (usual care). Paraprofessional counselors achieved independent ratings of adherence and competence equivalent to college-educated therapists in the United States. Treatment effect sizes were comparable to alcohol intervention studies conducted in the United States. CONCLUSIONS: Cognitive-behavioral therapy can be adapted successfully to group paraprofessional delivery in Kenya and may be effective in reducing alcohol use among HIV-infected Kenyan out-patients.

Role of low-frequency HIV-1 variants in failure of nevirapine-containing antiviral therapy in women previously exposed to single-dose nevirapine.

In the OCTANE/A5208 study of initial antiretroviral therapy (ART) in women exposed to single-dose nevirapine (sdNVP) ≥ 6 mo earlier, the primary endpoint (virological failure or death) was significantly more frequent in the NVP-containing treatment arm than in the lopinavir/ritonavir-containing treatment arm. Detection of NVP resistance in plasma virus at study entry by standard population genotype was strongly associated with the primary endpoint in the NVP arm, but two-thirds of endpoints occurred in women without NVP resistance. We hypothesized that low-frequency NVP-resistant mutants, missed by population genotype, explained excess failure in the NVP treatment arm. Plasma samples from 232 participants were analyzed by allele-specific PCR at study entry to quantify NVP-resistant mutants down to 0.1% for 103N and 190A and to 0.3% for 181C. Of 201 women without NVP resistance by population genotype, 70 (35%) had NVP-resistant mutants detected by allele-specific PCR. Among these 70 women, primary endpoints occurred in 12 (32%) of 38 women in the NVP arm vs. 3 (9%) of 32 in the lopinavir/ritonavir-containing arm (hazard ratio = 3.84). The occurrence of a primary endpoint in the NVP arm was significantly associated with the presence of K103N or Y181C NVP-resistant mutations at frequencies >1%. The risk for a study endpoint associated with NVP-resistant mutant levels did not decrease with time. Therefore, among women with prior exposure to sdNVP, low-frequency NVP-resistant mutants were associated with increased risk for failure of NVP-containing ART. The implications for choosing initial ART for sdNVP-exposed women are discussed.

Systematic cultural adaptation of cognitive-behavioral therapy to reduce alcohol use among HIV-infected outpatients in western Kenya.

Two-thirds of those with HIV worldwide live in sub-Saharan Africa. Alcohol use is associated with the HIV epidemic through risky sex and suboptimal ARV adherence. In western Kenya, hazardous drinking was reported by HIV (53%) and general medicine (68%) outpatients. Cognitive behavioral treatment (CBT) has demonstrated strong efficacy to reduce alcohol use. This article reports on a systematic cultural adaptation and pilot feasibility study of group paraprofessional-delivered CBT to reduce alcohol use among HIV-infected outpatients in Eldoret, Kenya. Following adaptation and counselor training, five pilot groups were run (n = 27). Overall attendance was 77%. Percent days abstinent from alcohol (PDA) before session 1 was 52-100% (women) and 21-36% (men), and by session 6 was 96-100% (women) and 89-100% (men). PDA effect sizes (Cohen's d) between first and last CBT session were 2.32 (women) and 2.64 (men). Participants reported treatment satisfaction. Results indicate feasibility, acceptability and preliminary efficacy for CBT in Kenya.

Renal disease in an antiretroviral-naïve HIV-infected outpatient population in Western Kenya.

BACKGROUND: Several commonly used antiretrovirals (ARVs) require dose adjustments to prevent toxicities in the presence of renal insufficiency. Because no prospective studies of the prevalence or risk factors for kidney disease in stable outpatient human immunodeficiency virus (HIV)-infected indigenous African populations have been published to date, it is not known if already scarce resources should be allocated to detect renal dysfunction, in those without risk factors for kidney disease, prior to initiation of increasingly available antiretrovirals in developing countries. METHODS: A cross-sectional study to determine the prevalence of and risk factors for renal disease in a cohort of medically stable, HIV-infected, antiretroviral-naïve adults, without diabetes or hypertension, presenting to an HIV clinic in western Kenya. RESULTS: Of 373 patients with complete data, renal insufficiency (CrCl <60 ml/min) was identified in 43 (11.5%) [18 (4.8%) had a CrCl <50 ml/min]. Despite high correlation coefficients between the three renal function estimating equations used, when compared to creatinine clearance as calculated by Cockcroft-Gault, lower rates of moderate to severe renal insufficiency were identified by the Modification of Diet in Renal Disease equations. Proteinuria, defined as a urine dipstick protein of equal to or greater than 1+, was detected in only 23 subjects (6.2%). CONCLUSIONS: Renal insufficiency is not uncommon, even in stable patients without diabetes or hypertension. Conversely, proteinuria was unexpectedly infrequent in this population. Utilizing resources to assess renal function prior to initiation of antiretrovirals in order to identify those likely to benefit from dosage adjustment is justified.