Inequality and private health insurance in Zimbabwe: history, politics and performance.

INTRODUCTION: Zimbabwe has one of the highest rates of private health insurance (PHI) expenditures as a share of total health expenditures in the world. The perfomamce of PHI, known as Medical Aid Societies in Zimbabwe, requires close monitoring since market failures and weaknesses in public policy and regulation can affect overall health system performance. Despite the considerable influence of politics (stakeholder interests) and history (past events) in shaping PHI design and implementation, these factors are frequently sidelined when analyzing PHI in Zimbabwe. This study considers the roles of history and politics in shaping PHI and determining its impact on health system performance in Zimbabwe. METHODS: We reviewed 50 sources of information using Arksey & O'Malley's (2005) methodological framework. To frame our analysis, we used a conceptual framework that integrates economic theory with political and historical aspects developed by Thomson et al. (2020) to analyze PHI in diverse contexts. RESULTS: We present a timeline of the history and politics of PHI in Zimbabwe from the 1930s to present. Zimbabwe's current PHI coverage is segmented along socio-economic lines due to a long history of elitist and exclusionary politics in coverage patterns. While PHI was considered to perform relatively well up to the mid-1990s, the economic crisis of the 2000s eroded trust among insurers, providers, and patients. That culminated in agency problems which severely lessened PHI coverage quality with concurrent deterioration in efficiency and equity-related performance dimensions. CONCLUSION: The present design and performance of PHI in Zimbabwe is primarily a function of history and politics rather than informed choice. Currently, PHI in Zimbabwe does not meet the evaluative criteria of a well-performing health insurance system. Therefore, reform efforts to expand PHI coverage or improve PHI performance must explicitly consider the relevant historical, political and economic aspects for successful reformation.

A framework for sustainable capacity-building for collaborative North-South translational health research and training in a resource-constrained setting.

INTRODUCTION: Success with highly active antiretroviral therapy (ART) for the human immunodeficiency virus (HIV) in developing countries has been attributed to collaborative North-South resource-sharing and capacity-building. Academic research and training programmes have contributed towards policy entrepreneurship in a manner that influenced capacity-building within health systems. However, the documented capacity-building frameworks rarely elucidate how such programmes can be designed and implemented efficiently and sustainably. METHOD: We implemented the University of Zimbabwe (UZ)-State University of New York at Buffalo (UB) collaborative HIV clinical pharmacology capacity-building programme in Zimbabwe in 1998. We intuitively operationalized the programme around a mnemonic acronym, "RSTUVW", which spells out a supportive framework consisting of "room (space), skills, tools (equipment)", underpinned by a set of core values, "understanding, voice (clout) and will". Subsequent to our two decades of successful collaborative experience, we tested the general validity and applicability of the framework within a prospective programme aimed at expanding the role of health professionals. RESULTS AND CONCLUSION: Based on this collaborative North-South research and training capacity-building programme which has been positively validated in Zimbabwe, we propose this novel mnemonic acronym-based framework as an extra tool to guide sustainable capacity-building through collaborative North-South implementation research. Its extended use could also include assessment and evaluation of health systems within resource-constrained settings.

Framing access to essential medicines in the context of Universal Health Coverage: a critical analysis of health sector strategic plans from eight countries in the WHO African region.

BACKGROUND: Framing affects how issues are understood and portrayed. This profoundly shapes the construction of social problems and how policy options are considered. While access to essential medicines (ATM) in the World Health Organization (WHO) African Region is often framed as a societal problem, there is dominance of medical and technically oriented approaches to analyze and remedy the situation. Hence, the systematic application of social science approaches, such as framing theory, remains under-explored. Through a framing analysis of National Strategic Plans (NSPs) from eight countries, this study explores the applicability and potential usefulness of framing theory to analyze essential medicines policies. METHODS: We inductively coded the relevant NSP textual fragments using the qualitative content analysis software ATLAS.ti.22. Benford and Snow's conceptualization of framing was used to organize the coded data into three frames: diagnostic (problems), prognostic (solutions) and motivational (values and ideological). RESULTS: The following five diagnostic frames were dominant or in-frame: medicine unavailability, ineffective regulation, weak supply chain management, proliferation of counterfeit (substandard or falsified) medicines and use of poor quality medicines. Diagnostic frames related to financing, affordability, efficiency and corruption were given limited coverage or out of frame. Prognostic frames corresponded with how these problems were framed. Whilst Universal Health Coverage (UHC) and its guiding principles was the dominant motivational frame, we identified some frame discordance between the global discourse and national level policies. CONCLUSIONS: Social science approaches such as framing analysis are applicable and useful to systematically analyze essential medicine aspects. By applying framing theory, we revealed that ATM aspects in the eight countries we analyzed are more often characterized in relation to availability at the expense of affordability which undermines UHC. We conclude that whilst UHC is a strong motivational frame to guide ATM aspects, it is insufficient to inform a comprehensive approach to address the problems related to ATM at country level. To effectively advance ATM, concerned actors need to realize such limitation and endeavor to gain a deeper understanding of how problems are framed and agendas are set at country level, the processes through which ideas and knowledge become policies, including the political demands, incentives and trade-offs facing decision-makers in selecting policy priorities.

Impact of Motivational Enhanced Adherence Counseling and Point-of-Care Viral Load Monitoring on Viral Load Outcome in Women on Life-Long ART: A Randomized Pilot Study.

We piloted the combined effectiveness of point-of-care viral load monitoring plus motivational enhanced adherence counseling (intervention) compared with routine care (control) in women identified at risk of virologic failure in the PROMOTE study in Zimbabwe. In an unblinded randomized study, consenting women with last viral load ≥200 copies/ml and/or pill count outside 90-110% range were randomized 1 : 1 to receive the intervention or continue routine care, comprising laboratory-based VL monitoring and standard EAC, from trained nurses and counsellors. Viral load was measured 0, 3, 6, and 12 months after enrolment. We compared viral suppression <200 copies/ml at 6 and 12 months between the arms through Fisher's exact test and sought associated factors by logistic regression with a 95% confidence interval (CI). Between December 2018 and July 2019, 50 women were enrolled (25 intervention and 25 controls) and followed until November 2020. At entry, 60% of the women were virally suppressed, 52% intervention vs. 68% control arm. Viral suppression was balanced between the two arms (p value = 0.248). At month 6 post study entry (primary endpont), 64% of the women retained in care were virally suppressed, 54% intervention vs. 76% control arm (p value = 0.124). At month12 post study entry (secondary endpoint), 69% of the women retained in care were virally suppressed, 67% intervention vs. 71% control arm women (p value = 0.739). More intervention women completed all scheduled sessions by month 6. Control group women were more likely to be virally suppressed at both timepoints. Only 25% had treatment switch by 12 months. Despite intense adherence support and viral load monitoring, sustained viral suppression remained elusive in women identified at risk of viral failure. These findings highlight the continued need for effective adherence intervention for women with unsuppressed HIV viral loads, efficient treatment switch strategies, as well as drug level monitoring.

The political economy of health financing reforms in Zimbabwe: a scoping review.

BACKGROUND: Implementation of health financing reforms for Universal Health Coverage (UHC) is inherently political. Despite the political determinants of UHC, health financing reform in Zimbabwe is often portrayed as a technical exercise with a familiar path of a thorough diagnosis of technical gaps followed by detailed prescriptions of reform priorities. In this study, we sought to understand the interaction between political and economic aspects of health financing reforms since the country got its independence in 1980. METHODS: We conducted a scoping review of health financing reforms in Zimbabwe and reviewed 84 relevant sources of information. We then conducted a thematic analysis using an adapted Fox and Reich's framework of ideas and ideologies, interests and institutions. RESULTS: We found that ideas, institutions and interests significantly influence health financing reforms in Zimbabwe with implications on health system performance. Reform priorities of the 1980s were influenced by socialist ideologies with an interest to address pervasive health inequities inherited from the colonial racial system. The progress in equity realized in the 1980s was severely disrupted from the 1990s partly due to neo-liberal ideologies which steered interests towards market-oriented reforms. The period from the 2000s is characterized by increasing donor influence on health financing and a cumulative socio-economic collapse that resulted in a sharp and protracted decline in health spending and widening of health inequities. CONCLUSION: Health financing reform process in Zimbabwe is heavily influenced by political economy characteristics which favor certain financing arrangements over others with profound implications on health system performance. We concluded that the political economy factors that slow down UHC reforms are not rooted in the ambiguities of ideas on what needs to be done. Instead, the missing link is how to move from intention to action by aligning espoused ideas with interests and institutions which is an inherently political and redistributive process. International and domestic actors involved in UHC in Zimbabwe  need to explicitly consider the politics of health financing reforms to improve the implementation feasibility of desired reforms.

The importance of prioritizing politics in Good Governance for Medicines Initiative in Zimbabwe: a qualitative policy analysis study.

In 2004, the World Health Organization (WHO) launched the Good Governance for Medicines (GGM) initiative, with the aim of fighting corruption in the pharmaceutical sector. In the case of Zimbabwe, implementation of the initiative slowed down after the development phase. Often, lack of funding and technical considerations are cited as major reasons for issue de-prioritization whilst ignoring the influence of politics in mediating policy diffusion. Between June and August 2021, we conducted an in-depth document review and interviewed individuals involved with GGM in Zimbabwe to understand the political determinants of GGM prioritization in Zimbabwe. To guide and direct our analysis, we used the Shiffman and Smith framework. We found that the inception of GGM was facilitated by capable leaders, effective guiding institutions and resonance of the idea with the political environment. Prioritization from inception to implementation was constrained by limited citizen engagement, restriction of the issue to the pharmaceutical domain and a political transition that re-oriented policy priorities and reconfigured individual actor power. The portrayal of corruption as a priority problem requiring policy action has been hampered by the political sensitivity of the issue, lack of credible indicators on the prevalence and severity of the problem and challenges to measure the effectiveness of interventions such as the GGM. Despite the slowdown, from 2018 GGM actors have taken advantage of momentous policy windows to reconstitute their power by opportunistically framing GGM within the broader framework of access to essential medicines leading to the creation of new policy alliances and establishment of strategic political structures. To sustain the political prioritization, actors need to lobby for the institutionalization of GGM within the Ministry of Health strategy, sensitize citizens on the initiative, involve multiple stakeholders and frame the issue as a strategic intervention that underpins pharmaceutical sector performance within the national developmental framework.

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.

Two decades (1998 to 2018) of collaborative human immunodeficiency virus clinical pharmacology capacity building in a resource constrained setting.

While important advances have been made in the prevention and treatment of Human Immunodeficiency Virus (HIV) infection, limited expertise and resource constraints to effectively manage rollout of HIV programs often contribute to poor treatment outcomes in Sub-Saharan Africa. In 1998, the University of Zimbabwe (UZ) and the University at Buffalo, State University of New York (UB), developed a collaborative clinical pharmacology capacity building program in Zimbabwe to train the next generation of HIV researchers and support rollout of the national HIV program. The collaboration was funded by research and training grants that were competitively acquired through United States of America government funding mechanisms, between 1998 and 2016. Thirty-eight research fellows were trained and a specialty clinical pharmacology laboratory was established during this period. Knowledge and skills transfer were achieved through faculty and student exchange visits. Scientific dissemination output included sixty-two scholarly publications that influenced three national policies and provided development of guidelines for strategic leadership for an HIV infection-patient adherence support group. The clinical pharmacology capacity building program trained fellows that were subsequently incorporated into the national technical working group at the Ministry of Health and Child Care, who are responsible for optimizing HIV treatment guidelines in Zimbabwe. Despite serious economic challenges, consistent collaboration between UZ and UB strengthened UZ faculty scholarly capacity, retention of HIV clinical research workforce was achieved, and the program made additional contributions toward optimization of antiretroviral therapy in Zimbabwe.

Cross-validation of a high-performance liquid chromatography nevirapine plasma assay in a resource-limited setting in Zimbabwe.

An international HIV pharmacology specialty laboratory (PSL) was established at the University of Zimbabwe to increase bioanalytical and investigator capacities. Quantitation of plasma nevirapine in samples from the AIDS Clinical Trials Group protocol 5279 was compared between the University of Nebraska Medical Center PSL and the University of Zimbabwe PSL. Both PSLs employed internally developed methods utilising reverse-phase high-performance liquid chromatography with ultraviolet detection. Eighty-seven percent of the cross-validation results exhibited ± 20% difference.

Agenda setting for essential medicines policy in sub-Saharan Africa: a retrospective policy analysis using Kingdon's multiple streams model.

BACKGROUND: Lack of access to essential medicines presents a significant threat to achieving universal health coverage (UHC) in sub-Saharan Africa. Although it is acknowledged that essential medicines policies do not rise and stay on the policy agenda solely through rational deliberation and consideration of technical merits, policy theory is rarely used to direct and guide analysis to inform future policy implementation. We used Kingdon's model to analyse agenda setting for essential medicines policy in sub-Saharan Africa during the formative phase of the primary healthcare (PHC) concept. METHODS: We retrospectively analysed 49 published articles and 11 policy documents. We used selected search terms in EMBASE and MEDLINE electronic databases to identify relevant published studies. Policy documents were obtained through hand searching of selected websites. We also reviewed the timeline of essential medicines policy milestones contained in the Flagship Report, Medicines in Health Systems: Advancing access, affordability and appropriate use, released by WHO in 2014. Kingdon's model was used as a lens to interpret the findings. RESULTS: We found that unsustainable rise in drug expenditure, inequitable access to drugs and irrational use of drugs were considered as problems in the mid-1970s. As a policy response, the essential drugs concept was introduced. A window of opportunity presented when provision of essential drugs was identified as one of the eight components of PHC. During implementation, policy contradictions emerged as political and policy actors framed the problems and perceived the effectiveness of policy responses in a manner that was amenable to their own interests and objectives. CONCLUSION: We found that effective implementation of an essential medicines policy under PHC was constrained by prioritization of trade over public health in the politics stream, inadequate systems thinking in the policy stream and promotion of economic-oriented reforms in both the politics and policy streams. These lessons from the PHC era could prove useful in improving the approach to contemporary UHC policies.

Survival of HIV-infected patients with high-grade non-Hodgkin's lymphomas: A retrospective study of experiences in Zimbabwe.

BACKGROUND: Rituximab in combination with chemotherapy is now widely accepted as standard of care for AIDS-related lymphomas (ARLs) of B-cell origin. However, the clinical impact of rituximab in resource limited settings remains unknown. Different settings and patient heterogeneity may affect the effect of any given treatment. The study objectives were to determine if rituximab use was associated with improved 18-month overall survival (OS) of patients with ARLs and to identify correlates of 18-month OS. METHODS: A retrospective review of medical records of adult HIV infected patients treated for high-grade large cell non-Hodgkin's lymphoma with chemotherapy +/- rituximab between 2015-2017 was conducted. Vital status and disease progression/relapse at 18 months were determined. Survival functions were estimated using Kaplan-Meier methodology. Equality of survival functions were assessed using Log-rank tests and Cox regression analysis to identify risk factors for mortality. RESULTS: One hundred and twenty-four eligible medical records were identified. This was a cohort of black Africans with a median age of 42 (IQR: 33-47) and a 57% male gender distribution. Overall survival at 6, 12 and 18 months for the population was 75.9%, 44.0% and 30.6% respectively. Over the study period, 72.6% of patients were diagnosed with disease progression/ relapse. There was a higher rate of rituximab use in patients who were treated at a private institution and those with medical insurance. Rituximab use was not associated with a reduction in 18-month mortality [adjusted hazard ratio (aHR)1.28, (95% CI 0.63-2.60)]. Risk factors for 18-month mortality were male gender [aHR 1.89, (95% CI 1.04-3.43)], age 40+ years [aHR 2.49, (1.33-4.67)], receipt of <3 chemotherapy cycles [aHR 2.48, (95% CI 1.33-4.60)] and low socioeconomic status [aHR 2.44, (95% CI 1.28-4.67)]. CONCLUSIONS: Predictors of mortality were male gender, older age, low socioeconomic status and receipt of a less than half of the recommended number of chemotherapy cycles. Rituximab use was not associated with an improvement in 18-month OS in Zimbabwean patients with ARLs.

Proximal renal tubular function in HIV-infected children on tenofovir disoproxil fumarate for treatment of HIV infection at two tertiary hospitals in Harare, Zimbabwe.

BACKGROUND: Renal abnormalities in HIV infected children may be due to the HIV infection or treatment among other factors. Tenofovir disoproxil fumarate (TDF) is associated with proximal renal tubular dysfunction, proteinuria and decrease in glomerular function. Studies in developed countries have shown variable prevalence of proximal renal tubular dysfunction in children on TDF. There are no known studies in developing countries, including Zimbabwe, documenting the proximal tubular function in HIV infected children on TDF. The aim of this study was to assess renal and proximal renal tubular function in HIV infected children receiving TDF and determine factors associated with proximal tubular dysfunction. METHODS: A descriptive cross-sectional study was conducted in HIV infected patients below 18 years of age attending outpatient clinics at two tertiary hospitals in Harare, who received a TDF-containing antiretroviral regimen for at least six months. Dipstick protein and glucose, serum and urine phosphate and creatinine levels were measured. Fractional excretion of phosphate was calculated. Estimated glomerular filtration rate (eGFR) was calculated using the Schwartz formula. Tubular dysfunction was defined by at least two of the following characteristics: normoglycaemic glycosuria, hypophosphatemia and fractional excretion of phosphate > 18%. FINDINGS: One hundred and ninety-eight children below 18 years of age were recruited over a period of six months. The prevalence of tubular dysfunction was 0.5%. Normoglycaemic glycosuria occurred in 1 (0.5%), fractional excretion of phosphate >18% in 4 (2%), and hypophosphatemia in 22 [11.1%] patients. Severe stunting was associated with increased risk of hypophosphatemia (OR 9.31 CI (1.18, 80.68) p = 0.03). Reduction in estimated glomerular filtration rate (eGFR) < 90ml/min/1.73m2 and proteinuria was evident in 35.9% and 32.8% of children, respectively. Concurrent TDF and HIV-1 protease inhibitor-based regimen was the only independent factor associated with reduction in GFR (OR 4.43 CI (1.32; 4.89) p = 0.016). CONCLUSION: Tubular dysfunction was uncommon in Zimbabwean children on a TDF-based ART regimen. Hypophosphatemia, proteinuria and reduction in eGFR were common. Reassessing renal function using more sensitive biomarkers is needed to examine the long-term tolerance of TDF.

Acceptability of donor breastmilk banking among health workers: a cross-sectional survey in Zimbabwean urban settings.

BACKGROUND: The World Health Organization (WHO) recommends that donor human milk is superior to artificial infant formula in situations where the baby cannot feed on the mother's breastmilk. The purpose of this study was to determine the acceptability of donor human milk banking among health workers in Zimbabwean urban settings. METHODS: A cross sectional study was conducted among 535 health workers and 15 key informants. Three referral hospitals were purposively selected and systematic random sampling was used to select the health workers. The study was conducted between October 2017 and October 2018. RESULTS: The concept of donor human milk banking was acceptable among health workers. One-third (31%) of the study participants reported that they would accept donor breastmilk for their children while 56% of them would encourage their clients to donate breastmilk. Acceptance of donor human milk banking was associated with a high level of knowledge on breastmilk banks (p = 0.009) and the study participants' health profession (p = 0.001). Clinical staff were more receptive to donor human milk banking compared to non-clinical health workers. Donor human milk banking was not associated with religion (p = 0.498) or marital status (p = 0.714). CONCLUSIONS: The results showed that health workers and policy informers would accept the establishment of breastmilk banks subject to resource availability. Commitment to the establishment of breastmilk banks was moderately acceptable among opinion leaders responsible for spearheading health and nutrition policies.

Perspectives on oral pre-exposure prophylaxis use amongst female sex workers in Harare, Zimbabwe.

BACKGROUND: Pre-exposure prophylaxis (PrEP) could provide protection from human immunodeficiency virus (HIV) infection in sexually active persons at risk. Limited data are available in Zimbabwe with regard to the perceptions about PrEP amongst female sex workers (FSWs). OBJECTIVES: The aim of this study was to evaluate the knowledge levels of oral PrEP and the likelihood of its use amongst FSWs. METHOD: This was a cross-sectional study in the peri-urban areas of Harare, Zimbabwe. Human immunodeficiency virus-negative FSWs were interviewed to assess their awareness of and likelihood to use PrEP. The relative importance index was used to evaluate the levels of knowledge and the likelihood of, and barriers to, PrEP use. A set of 10 questions was designed and validated that evaluated participants' understanding of PrEP. A bivariate logistic regression model was utilised to identify predictors of PrEP use. RESULTS: A total of 131 FSWs with a median age of 25 years (interquartile range: 21-31) participated in this study. Of the 71 (54%) FSWs who had heard about PrEP, 46 (35%) participants had adequate knowledge of its use. A total of 102 (78%) participants revealed that they would be willing to continuously use PrEP if it was provided free of cost. Increasing age of the participants was associated with an increase in the likelihood of using PrEP (r = 0.0033, p = 0.038). More knowledge about PrEP increased the likelihood of its use (r = 0.21, p = 0.0153). This likelihood increased amongst participants with an unprotected sexual intercourse encounter in the preceding 3 months (r = 0.0448, p = 0.026). CONCLUSION: Knowledge of PrEP amongst FSWs was low. To increase the uptake of PrEP, there is a need to further sensitise FSWs about this intervention. Programmes should also promote awareness training in FSW subgroups that are less likely to use PrEP.

Mentored postdoctoral training in Zimbabwe: A report on a successful collaborative effort.

Low-and-middle-income countries (LMICs) have high disease burdens, necessitating increased research. However, LMIC research output constitutes only 2% of global total. To increase output, researchers must be capacitated. The University of Zimbabwe (UZ) and the University at Buffalo (UB), developed and implemented the AIDS International Research Training Program (AITRP), in 2008, that focused on graduate scholars. The subsequent HIV Research Training Program (HRTP), begun in 2016, and piloted post-doctoral training to enhance research productivity at UZ. This report discusses the collaboration. As of 2016, prospective candidates applied by submitting letters of intent, research proposals, curriculum vitae and biographical sketches. The scholars research training included hypothesis and project development, completion of grant applications, research project budgets, research presentations to diverse audiences and the application of advanced statistics to research data. The first cohort of five postdoctoral scholars were trained at UZ and UB, between 2016 and 2019. Through the formalized postdoctoral training approach, scholars identified areas of focus. In 2017, one of the scholars obtained a National Institutes of Health (NIH) Emerging Global Leader Award and is now a highly-rated researcher based in South Africa. A second scholar made NIH D43 and K43 grant applications, while the remaining three are academicians and early researchers at UZ. Although research output in Africa and many LMICs is low, it can be built through cooperation similar to the UZ-UB HRTP. This manuscript reports on an effort aimed at building individual and institutional research capacity in Zimbabwe. This can serve as a model for building other similar training programs.

Cognitive-Enhancing Effect of a Hydroethanolic Extract of Crinum macowanii against Memory Impairment Induced by Aluminum Chloride in BALB/c Mice.

Crinum macowanii is a bulbous plant indigenous to many parts of Southern Africa. Extracts of C. macowanii have gained interest since the discovery of various alkaloids, few of which possess acetylcholinesterase inhibitory activity. The present study was performed to evaluate the effect of a crude hydroethanolic extract of C. macowanii against aluminum chloride-induced memory impairment in mice using the Morris water maze and the novel object recognition task. C. macowanii (10, 20, and 40 mg/kg p.o) was administered daily for five weeks, while donepezil (3 mg/kg p.o) was used as the positive control. C. macowanii at a dosage of 40 mg/kg showed a significantly lower escape latency than the negative control (P < 0.0001) and was found to be comparable to donepezil 3 mg/kg in the Morris water maze test. C. macowanii at 40 mg/kg exhibited a significantly higher discrimination index than aluminum chloride-treated mice in the novel object recognition task. The results may support the usefulness of C. macowanii in the management of dementia and related illnesses.

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

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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).

Capacity for ethical and regulatory review of herbal trials in developing countries: a case study of Moringa oleifera research in HIV-infected patients.

BACKGROUND: Lack of regulatory capacity limits the conduct of ethical and rigorous trials of herbal medicines in developing countries. Sharing ethical and regulatory experiences of successful herbal trials may accelerate the field while assuring human subjects protection. The methods and timelines for the ethical and regulatory review processes for the first drug regulatory authority approved herbal trial in Zimbabwe are described in this report. METHODS: The national drug regulatory authority and ethics committee were engaged for pre-submission discussions. Six applications were submitted. Application procedures and communications with the various regulatory and ethics review boards were reviewed. Key issues raised and timelines for communications were summarized. RESULTS: There was no special framework for the approval of herbal trials. One local institutional review committee granted an exemption. Key issues raised for revision were around pre-clinical efficacy and safety data, standardization and quality assurance of the intervention as well as consenting procedures. Approval timelines ranged between eight and 72 weeks. CONCLUSIONS: In the absence of a defined framework for review of herbal trials, approval processes can be delayed. Dialogue between researchers and regulators is important for successful and efficient protocol approval for herbal trials in developing countries. TRIAL REGISTRATION: The study was registered prospectively on August 3, 2011 with clinicaltrials.gov (NCT01410058).

Poly(lactic-co-glycolic) Acid-Chitosan Dual Loaded Nanoparticles for Antiretroviral Nanoformulations.

Poly(lactic-co-glycolic acid) (PLGA) chitosan (CS) coated nanoparticles (NPs) were loaded with two antiretrovirals (ARVs) either lamivudine (LMV) which is hydrophilic or nevirapine (NVP) which is hydrophobic or both LMV and NVP. These ARVs are of importance in resource-limited settings, where they are commonly used in human immunodeficiency virus (HIV-1) treatment due to affordability and accessibility. NPs prepared by a water-oil-water emulsion and reduced pressure solvent evaporation technique were determined to have a positive zeta potential, a capsule-like morphology, and an average hydrodynamic diameter of 240 nm. Entrapment of NVP as a single ARV had a notable increase in NP size compared to LMV alone or in combination with LMV. NPs stored at room temperature in distilled water maintained size, polydispersity (PDI), and zeta potential for one year. No changes in size, PDI, and zeta potential were observed for NPs in 10% sucrose in lyophilized or nonlyophilized states stored at 4°C and -20°C, respectively. Freezing NPs in the absence of sucrose increased NP size. Drug loading, encapsulation efficiency, and kinetic release profiles were quantified by high performance liquid chromatography (HPLC). Our novel nanoformulations have the potential to improve patient outcomes and expand drug access in resource-limited countries for the treatment of HIV-1.

Macrophage Targeted Nanoparticles for Antiretroviral (ARV) Delivery.

OBJECTIVE: To reduce the amount of the antiretroviral (ARV) nevirapine necessary to achieve therapeutic concentrations using macrophage targeted nanoparticles. METHODS: Core-shell nanoparticles were prepared from FDA approved, biodegradable and biocompatible polymers, with poly(lactic-co-glycolic) acid (PLGA) as the core and chitosan (CS) as the shell using a water/oil/water method. Nevirapine was encapsulated in the core of the nanoparticles. ß-glucan (GLU) was adsorbed to the surface of the nanoparticle. Macrophage uptake and intracellular nevirapine concentrations were determined by fluorescence imaging and ultra-performance liquid chromatography/mass spectroscopy (UPLC-MS). Optical imaging was employed to characterize the biodistribution of nanoparticles following intravenous injection in CD-1 mice. RESULTS: We synthesized spherical shaped 190 nm GLU-CS-PLGA nanoparticles that provide controlled release of nevirapine. In THP-1 macrophage the uptake of PLGA and CS- PLGA nanoparticles was less compared to targeted GLU-CS-PLGA nanoparticles. THP-1 macrophage were dosed with free nevirapine (10 µg/well) and GLU-CS- PLGA nanoparticles containing 1/10 the concentration of free nevirapine (1 µg nevirapine/well). The intracellular concentration of nevirapine was the same for both nanoparticles and free nevirapine at 2 and 24 hrs. No significant change in THP-1 macrophage viability was observed in the presence of nanoparticles relative to the control. Ex vivo imaging demonstrates that nanoparticles are predominantly found in the liver and kidney and at 24 hr there is still a large amount of nanoparticles in the body. CONCLUSION: These data demonstrate that the total dose of nevirapine delivered by GLU-CS-PLGA nanoparticles can be greatly reduced, to limit side effects, while still providing maximal ARV activity in a known cellular reservoir.