The Impact of Herbal Drug Use on Adverse Drug Reaction Profiles of Patients on Antiretroviral Therapy in Zimbabwe

Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART). Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2%) of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%), Bidens pilosa (66.0%), Eucalyptus globulus (52.3%), Moringa oleifera (44.1%), Lippia javanica (36.3%), and Peltoforum africanum (34.3%). Two indigenous herbs, Musakavakadzi (OR = 0.25; 95% CI 0.076–0.828) and Peltoforum africanum (OR = 0.495; 95% CI 0.292–0.839) reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles

Antiretroviral drug levels and interactions affect lipid, lipoprotein, and glucose metabolism in HIV-1 seronegative subjects: A pharmacokinetic- pharmacodynamic analysis

BACKGROUND: HIV-infected patients treated with antiretroviral medications (ARVs) develop undesirable changes in lipid and glucose metabolism that mimic the metabolic syndrome and may be proatherogenic. Antiretroviral drug levels and their interactions may contribute to these metabolic alterations. METHODS: Fifty-six HIV-seronegative adults were enrolled in an open-label, randomized, pharmacokinetic interaction study, and received a non-nucleoside reverse transcriptase inhibitor (efavirenz on days 1-21) plus a protease inhibitor (PI; amprenavir on days 11-21), with a second PI on days 15-21 (saquinavir, nelfinavir, indinavir, or ritonavir). Fasting triglycerides, total, LDL- and HDL-cholesterol, glucose, insulin and C-peptide levels were measured on days 0, 14, 21, and 2-3 weeks after discontinuing drugs. Regression models were used to estimate changes in these parameters and associations between these changes and circulating levels of study drugs. RESULTS: Short-term efavirenz and amprenavir administration significantly increased cholesterol, triglycerides and glucose levels. Addition of a second protease inhibitor further increased triglycerides, total- and LDL-cholesterol levels. Higher amprenavir levels predicted larger increases in triglycerides, total and LDL-cholesterol. Two weeks after all study drugs were stopped, total, LDL- and HDL-cholesterol remained elevated above baseline. CONCLUSIONS: ARV regimens that include a non-nucleoside reverse transcriptase inhibitor plus single or boosted PIs are becoming more common, but the pharmacodynamic interactions associated with these regimens can result in persistent, undesirable alterations in serum lipid/lipoprotein levels. Additional pharmacodynamic studies are needed to examine the metabolic effects of ritonavir-boosted regimens, with and without efavirenz

Novel Considerations about Diabetes Management Strategies in Chinese Immigrants in America: Possible Corollaries of the Use of Traditional Chinese Medicines

Worldwide, the prevalence of type 2 diabetes mellitus (T2DM) and its related management costs have increased over time. The latest predictions anticipate this trend to continue during the next few decades. As individuals with T2DM in the United States (US) are burdened with escalating prescription drug expenses, the appeal and use of cost effective alternatives may also increase. Herbal supplements are an example of such an alternative, but are unregulated and mostly lacking scientific evidence of advertised claims. In general, plant based herbal preparations are often advertised as ‘natural’, ‘less-toxic’, ‘medicines’ and are widely available from public retailers throughout the country. Over half of the US adult population report the use of supplements. Eastern countries, and especially China, have a long history of the use of herbal preparations as traditional medicine to prevent and treat diabetes. Recently the US has experienced a growth in the number imports of herbal supplements and other Traditional Chinese Medicines (TCM) to the country as well as the most rapid population growth in individuals who identify themselves as Asian. To date, little is known about the prevalence TCM use in the management of T2DM either alone or in combination with prescription medicines in the US. Knowledge of possible implications to patient safety (e.g., interactions, adverse effects) with concurrent use of both TCM and prescription medicines is also lacking. This review begins with summaries of the T2DM management strategies employed in traditional modern medicine (TMM) and Chinese medicine (TCM). A review of literature follows where the most commonly used TCM herbal preparations and their ingredients are identified and found along with any published reports of their proposed mechanisms of action, efficacy, adverse effects, and contraindications. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties.   Type: Revie

Novel Considerations about Diabetes Management Strategies in Chinese Immigrants in America: Possible Corollaries of the Use of Traditional Chinese Medicines

Worldwide, the prevalence of type 2 diabetes mellitus (T2DM) and its related management costs have increased over time. The latest predictions anticipate this trend to continue during the next few decades. As individuals with T2DM in the United States (US) are burdened with escalating prescription drug expenses, the appeal and use of cost effective alternatives may also increase. Herbal supplements are an example of such an alternative, but are unregulated and mostly lacking scientific evidence of advertised claims. In general, plant based herbal preparations are often advertised as ‘natural’, ‘less-toxic’, ‘medicines’ and are widely available from public retailers throughout the country. Over half of the US adult population report the use of supplements. Eastern countries, and especially China, have a long history of the use of herbal preparations as traditional medicine to prevent and treat diabetes. Recently the US has experienced a growth in the number imports of herbal supplements and other Traditional Chinese Medicines (TCM) to the country as well as the most rapid population growth in individuals who identify themselves as Asian. To date, little is known about the prevalence TCM use in the management of T2DM either alone or in combination with prescription medicines in the US. Knowledge of possible implications to patient safety (e.g., interactions, adverse effects) with concurrent use of both TCM and prescription medicines is also lacking. This review begins with summaries of the T2DM management strategies employed in traditional modern medicine (TMM) and Chinese medicine (TCM). A review of literature follows where the most commonly used TCM herbal preparations and their ingredients are identified and found along with any published reports of their proposed mechanisms of action, efficacy, adverse effects, and contraindications. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties.   Type: Revie

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

Moringa 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. Adult 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). Pharmacokinetics 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. Co-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

Comparative Effectiveness of Darunavir 1,200 mg Daily and Approved Dosing Strategies for Protease Inhibitor-Experienced Patients

Background. HIV protease inhibitors exhibit concentration-dependent viral inhibition. Higher once daily doses of darunavir boosted with ritonavir (DRV/r) may achieve viral suppression in place of twice daily dosing. International antiretroviral adherence guidelines recommend once daily regimens whenever possible. We present data on virologic suppression achieved with DRV 1,200 mg and ritonavir 100 mg once daily compared to approved DRV regimens. Methods. This retrospective observational study included all patients treated with DRV after documented use of another protease inhibitor at an urban immunodeficiency clinic. Data collection from inception of DRV use in August 2006 through March 2012 included patient demographics, viral loads, CD4+ cell counts, and resistance test results. The primary outcome of virologic suppression was defined as <50 copies/mL at 24 weeks. Differences in baseline characteristics and virologic outcomes across dosing groups were analyzed via one-way analysis of variance. Results. One hundred and thirty-five patients were included in the ITT analysis. Most patients had no known DRV RAMs at baseline. Virologic suppression rate was not different among treatment groups: 53.6% of patients on 1,200 mg daily, 52.3% on 600 mg twice daily, and 42.9% on 800 mg daily (P = 0.568). Conclusions. Darunavir 1,200 mg daily should be investigated for use in protease inhibitor-experienced patients

Bone mineral density reductions after tenofovir disoproxil fumarate initiation and changes in phosphaturia: a secondary analysis of ACTG A5224s

Background: It is unknown if the greater reductions in bone mineral density (BMD) associated with initiation of tenofovir disoproxil fumarate compared with abacavir in previously untreated HIV-infected participants in the ACTG A5224s clinical trial were associated with potentially worsening tenofovir-related phosphaturia. Methods: We correlated changes in BMD at the hip and spine with changes in phosphaturia [transtubular reabsorption of phosphorus (TRP) and tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR)] from entry through week 96 in those initiating tenofovir ( n  =   134) versus abacavir ( n  =   135) with efavirenz or atazanavir/ritonavir in A5224s. We also correlated changes in BMD with tenofovir AUC measured between weeks 4 and 24. Results: Changes in TRP and TmP/GFR through week 96 between the tenofovir and abacavir arms were not significantly different (both P  ≥   0.70) and did not differ with use of efavirenz versus atazanavir/ritonavir. There were no significant correlations between changes in either TRP or TmP/GFR and with either hip or spine BMD in the tenofovir arms. Tenofovir AUC was significantly correlated with changes in hip BMD, but not spine BMD, at week 24 ( r  =   -0.22, P  =   0.028) and week 48 ( r  =   -0.26, P  =   0.010), but not at week 96 ( r  =   -0.14, P  =   0.18). Conclusions: Changes in phosphaturia were not different between the tenofovir and abacavir arms in A5224s. Changes in hip and spine BMD with tenofovir were not related to changes in phosphaturia. However, tenofovir exposure was weakly associated with changes in hip BMD through week 48

Amprenavir and efavirenz pharmacokinetics before and after the addition of nelfinavir, indinavir, ritonavir, or saquinavir in seronegative individuals

Adult AIDS Clinical Trials Group 5043 examined pharmacokinetic (PK) interactions between amprenavir (APV) and efavirenz (EFV) both by themselves and when nelfinavir (NFV), indinavir (IDV), ritonavir (RTV), or saquinavir (SQV) is added. A PK study was conducted after the administration of single doses of APV (day 0). Subjects (n = 56) received 600 mg of EFV every 24 h (q24h) for 10 days and restarted APV with EFV for days 11 to 13 with a PK study on day 14. A second protease inhibitor (PI) (NFV, 1,250 mg, q12h; IDV, 1,200 mg, q12h; RTV, 100 mg, q12h; or SQV, 1,600 mg, q12h) was added to APV and EFV on day 15, and a PK study was conducted on day 21. Controls continued APV and EFV without a second PI. Among subjects, the APV areas under the curve (AUCs) on days 0, 14, and 21 were compared using the Wilcoxon signed-rank test. Ninety-percent confidence intervals around the geometric mean ratios (GMR) were calculated. APV AUCs were 46% to 61% lower (median percentage of AUC) with EFV (day 14 versus day 0; P values of <0.05). In the NFV, IDV, and RTV groups, day 21 APV AUCs with EFV were higher than AUCs for EFV alone. Ninety-percent confidence intervals around the GMR were 3.5 to 5.3 for NFV (P < 0.001), 2.8 to 4.5 for IDV (P < 0.001), and 7.8 to 11.5 for RTV (P = 0.004). Saquinavir modestly increased the APV AUCs (GMR, 1.0 to 1.4; P = 0.106). Control group AUCs were lower on day 21 compared to those on day 14 (GMR, 0.7 to 1.0; P = 0.042). African-American non-Hispanics had higher day 14 efavirenz AUCs than white non-Hispanics. We conclude that EFV lowered APV AUCs, but nelfinavir, indinavir, or ritonavir compensated for EFV induction

Interaction of Disulfiram with Antiretroviral Medications: Efavirenz Increases While Atazanavir Decreases Disulfiram Effect on Enzymes of Alcohol Metabolism

Background and Objectives Alcohol abuse complicates treatment of HIV disease and is linked to poor outcomes. Alcohol pharmacotherapies, including disulfiram (DIS), are infrequently utilized in co-occurring HIV and alcohol use disorders possibly related to concerns about drug interactions between antiretroviral (ARV) medications and DIS. Method This pharmacokinetics study (n = 40) examined the effect of DIS on efavirenz (EFV), ritonavir (RTV), or atazanavir (ATV) and the effect of these ARV medications on DIS metabolism and aldehyde dehydrogenase (ALDH) activity which mediates the DIS-alcohol reaction. Results EFV administration was associated with decreased S-Methyl-N-N-diethylthiocarbamate (DIS carbamate), a metabolite of DIS (p = .001) and a precursor to the metabolite responsible for ALDH inhibition, S-methyl-N,N-diethylthiolcarbamate sulfoxide (DETC–MeSO). EFV was associated with increased DIS inhibition of ALDH activity relative to DIS alone administration possibly as a result of EFV-associated induction of CYP 3A4 which metabolizes the carbamate to DETC–MeSO (which inhibits ALDH). Conversely, ATV co-administration reduced the effect of DIS on ALDH activity possibly as a result of ATV inhibition of CYP 3A4. DIS administration had no significant effect on any ARV studied. Discussion/Conclusions ATV may render DIS ineffective in treatment of alcoholism. Future Directions DIS is infrequently utilized in HIV-infected individuals due to concerns about adverse interactions and side effects. Findings from this study indicate that, with ongoing clinical monitoring, DIS should be reconsidered given its potential efficacy for alcohol and potentially, cocaine use disorders, that may occur in this population. (Am J Addict 2014;23:137–144

Utility of HIV support groups in advancing implementation research in resource-limited settings: experiences from an urban-setting HIV support group in Zimbabwe.

Support groups for people living with the Human Immunodeficiency Virus (HIV) have continued to evolve since their emergence over two decades ago. In addition to providing HIV education and fostering psychosocial support, recent efforts have shifted the focus to socio-economic activities and retention in care. The sense of urgency to adopt new treatment and prevention strategies in sub-Saharan Africa necessitates greater engagement of established HIV care programs, especially among researchers seeking to conduct implementation research, promote prevention strategies and optimize treatment as prevention. To maximize the utility of support groups in doing so, efforts to create an organized, collaborative framework should be considered. This paper aims to describe the process of refocusing an adult HIV peer-support group and illustrate how a structured program was strengthened to sustain implementation research in resource-limited settings, while promoting patient recruitment and retention. A multidisciplinary team of scientists supporting an HIV peer-support group spearheaded the implementation process that authored the successes, challenges and lessons documented over eight years. Psychosocial support, nutrition care and support, adherence education and income generating projects were the main interventions employed. The initiative resulted in seven peer-reviewed publications, submission of 23 scientific abstracts, scientific dissemination at 12 international conferences. Eleven research studies and 16 income generating projects were successfully conducted over eight years. More than 900 patients participated in peer-support group activities every month and 400 were engaged in income generating activities. This multidisciplinary structured program was valuable in the retention and recruitment of patients for implementation research and benefits extended to psychosocial support, microeconomic projects, and improved nutrition. The support group contributed to strengthening implementation research through providing a platform for identification of research priorities, patient recruitment and retention in studies and dissemination of research findings