CYP2D6*17 polymorphism and tardive dyskinesia in black psychotic patients on typical antipsychotics

Background: Tardive dyskinesia is a debilitating, intractable, hyperkinetic movement disorder which contributes to an increase in psychiatric morbidity. Reduced function CYP2D6 alleles have been associated with tardive dyskinesia pathogenesis amongst Caucasians and Asians, with CYP2D*4 and *6 and CYP2D6*10 being implicated in these races respectively. No similar study has been successfully conducted in black Africans. Objective: To determine the relationship between tardive dyskinesia and CYP2D6*17 (the major reduced function CYP2D6 allele in Africans). Methodology: Abnormal Involuntary Movements Scale (AIMS) scoring and CYP2D6 genotyping were carried out on psychiatric patients exposed to typical antipsychotic medications in an unmatched case control study. A case of tardive dyskinesia was defined as a patient with an AIMS score ≥ 2 in two body areas OR ≥ 3 in one body area Results: A total of 18 cases and 32 controls made up the study sample.The sample’s mean age was 36.9±12.0 years with median treatment duration of 7.0 years (range: 0.25 to 38 years). Multiple logistic regression revealed no significant association between tardive dyskinesia and CYP2D6*17 (OR=0.252; 95% CI: 0.038 to 1.647; p=0.150). However, use of chlorpromazine (OR=5.754; 95% CI: 1.024 to 32.328; p=0.047) and age at treatment initiation (OR=1.146; 95% CI: 1.021 to 1.287; p=0.021) were independent predictors of tardive dyskinesia. Discussion: These findings suggest that there is no association between CYP2D6*17and tardive dyskinesia in African psychotic patients on typical antipsychotics. However, more studies with larger sample sizes are required to provide more definitive conclusions regarding the nature of the relationship betweenCYP2D6*17 and tardive dyskinesia. Key words: Tardive dyskinesia, CYP2D*17, typical antipsychotic

Routine prophylactic antibiotic use in the management of snakebite

BACKGROUND: Routine antibiotic prophylaxis following snakebite is not recommended but evidence suggests that it may be common practice in Zimbabwe. This study set out to determine and describe the extent of this practice at Parirenyatwa Hospital, a large teaching hospital in Zimbabwe METHODS: A retrospective case review (1996 to 1999 inclusive) of all cases of snakebite was undertaken at Parirenyatwa Hospital. Cases with a diagnosis of snakebite, presenting within 24 hours of the bite and with no complications or concurrent illness were defined as "routine prophylactic antibiotic use". RESULTS: From 78 cases which satisfied the inclusion criteria, 69 (88.5%) received antibiotics. Ten different antibiotics from 6 different classes were used with penicillins the most commonly prescribed (benzylpenicillin in 29% of cases, alone or in combination). Over 40% of antibiotics were given parenterally although all patients were conscious on admission. The total cost of antibiotics used was estimated at US$522.98. CONCLUSION: Routine prophylactic use of antibiotics in snakebite at Parirenyatwa Hospital is common practice. This may highlight the lack of a clearly defined policy leading to wasteful inappropriate antibiotic use which is costly and may promote bacterial antibiotic resistance. Further work is required to investigate the reasons for this practice and to design appropriate interventions to counter it

Effect of Moringa oleifera Lam. leaf powder on the pharmacokinetics of nevirapine in HIV-infected adults: a one sequence cross-over study.

BackgroundMoringa oleifera Lam., an herb commonly consumed by HIV-infected people on antiretroviral therapy, inhibits cytochrome P450 3A4, 1A2 and 2D6 activity in vitro; and may alter the pharmacokinetics (PK) of antiretroviral drugs metabolized via the same pathways. However, in vitro drug interaction activity may not translate to a clinically significant effect. Therefore, the effect of moringa leaf powder on the PK of nevirapine in HIV-infected people was investigated.MethodsAdult patients at steady-state dosing with nevirapine were admitted for 12-h intensive PK sampling following a 21-day herbal medicine washout. Blood sampling was repeated after 14 days of nevirapine and moringa (1.85 g leaf powder/day) co-administration. Nevirapine plasma concentrations were determined by liquid chromatography-tandem mass spectrometry. To assess the effect of moringa on nevirapine PK, the change in nevirapine area under the plasma concentration-time curve (AUC) was determined. The mean difference in pre- and post-moringa nevirapine, maximum concentration (Cmax) and concentration at 12 h (C12h) were also calculated. The PK parameters were compared by assessing the post/pre geometric mean ratios (GMRs) and associated 90% confidence intervals (CIs).ResultsPharmacokinetics analyses were performed on the results from 11 participants for whom complete data were obtained. The post/pre GMRs and associated 90% CIs for nevirapine were 1.07 (1.00-1.14) for the AUC; 1.06 (0.98-1.16) for Cmax and 1.03 (0.92-1.16) for C12h.ConclusionCo-administration of Moringa oleifera Lam. leaf powder at the traditional dose did not significantly alter the steady-state PK of nevirapine. Trial registration number NCT01410058 (ClinicalTrials.gov)

Ritonavir concentrations in hair predict virologic outcomes in HIV-infected adolescents with virologic failure on atazanavir/ritonavir-based second-line treatment.

BACKGROUND: Sub-optimal adherence to antiretroviral therapy (ART) is responsible for most virologic failure among adolescents with HIV. Methods for objectively measuring adherence to ART are limited. This study assessed the association between ritonavir concentrations in hair, self-reported adherence and modified directly administered antiretroviral therapy on virologic outcomes among HIV-infected adolescents who were virologically failing second-line ART in Harare, Zimbabwe. METHODS: HIV-infected adolescents on atazanavir/ritonavir-based second-line treatment for >6 months with viral load ≥1,000 copies/mL were randomized to either modified directly administered antiretroviral therapy (mDAART) plus standard-of-care (intervention) or standard-of-care alone (control). Questionnaires were administered; viral load and hair samples were collected at baseline and after 90 days. Virological suppression was defined as <1,000 copies/mL after follow-up. RESULTS: Fifty adolescents (13–19 years old) were enrolled, and 42 adolescents had ritonavir concentrations measured in hair at baseline and 90 days. Twenty-three (46%) were randomised to mDAART. Viral load suppression at follow-up [regression co-efficient(standard error); 95% confidence interval; p-value] [−0.3(0.1); −0.5- −0.06; 0.01], self-reported adherence at follow-up [0.01(0.005); 0.004–0.02; 0.006] and being male [0.3(0.1); 0.08–0.5; 0.008] were associated with ritonavir concentrations in hair. The intervention, mDAART, was not associated with ritonavir concentrations [0.2(0.1); −0.07–0.4; 0.2]. CONCLUSION: Ritonavir concentrations in hair predicted virological suppression and were associated with self-reported adherence and being male in this cohort of adolescents with treatment failure to atazanavir/ritonavir-based second-line ART. Measuring ritonavir concentrations in hair in adolescents on protease inhibitor-based regimens could assess adherence in this vulnerable group to avert subsequent virologic failure

Defining a Cutoff for Atazanavir in Hair Samples Associated With Virological Failure Among Adolescents Failing Second-Line Antiretroviral Treatment.

BackgroundAdequate antiretroviral exposure is crucial to virological suppression. We assessed the relationship between atazanavir hair levels with self-reported adherence, virological outcomes, and the effect of a home-based adherence intervention in HIV-infected adolescents failing second-line antiretroviral treatment in Zimbabwe.MethodsHIV-infected adolescents on atazanavir/ritonavir-based second-line treatment for ≥6 months with viral load (VL) &gt;1000 copies/mL were randomized to either standard care (control) or standard care plus modified directly administered antiretroviral therapy (intervention). Questionnaires were administered; VL and hair samples were collected at baseline and after 90 days in each group. Viral suppression was defined as &lt;1000 copies/mL after follow-up.ResultsFifty adolescents (10-18 years) were enrolled; 23 (46%) were randomized to intervention and 27 (54%) to control. Atazanavir hair concentration &lt;2.35 ng/mg (lower interquartile range for those with virological suppression) defined a cutoff below which most participants experienced virological failure. Male sex (P = 0.03), virological suppression at follow-up (P = 0.013), greater reduction in VL (P = 0.006), and change in average self-reported adherence over the previous month (P = 0.031) were associated with adequate (&gt;2.35 ng/mg) hair concentrations. Participants with virological failure were more likely to have suboptimal atazanavir hair concentrations (RR = 7.2, 95% CI: 1 to 51, P = 0.049). There were no differences in atazanavir hair concentration between the arms after follow-up.ConclusionsA threshold of atazanavir concentrations in hair (2.35 ng/mg), above which virological suppression was likely, was defined for adolescents failing second-line atazanavir/ritonavir-based ART in Zimbabwe. Male sex and better self-reported adherence were associated with adequate atazanavir hair concentrations. Antiretroviral hair concentrations may serve as a useful clinical tool among adolescents