Are Fc gamma receptor polymorphisms important in HIV-1 infection outcomes and latent reservoir size?

Fc gamma receptors (FcγR) are cell surface glycoproteins which trigger specific effector-cell responses when cross-linked with the Fc portions of immunoglobulin (IgG) antibodies. During HIV-1 infection, the course of disease progression, ART response, and viral reservoir size vary in different individuals. Several factors may account for these differences; however, Fc gamma receptor gene polymorphisms, which influence receptor binding to IgG antibodies, are likely to play a key role. FcγRIIa (CD32) was recently reported as a potential marker for latent HIV reservoir, however, this assertion is still inconclusive. Whether FcγR polymorphisms influence the size of the viral reservoir, remains an important question in HIV cure studies. In addition, potential cure or viral suppression methods such as broadly neutralizing antibody (bNAbs) may depend on FcγRs to control the virus. Here, we discuss the current evidence on the potential role played by FcγR polymorphisms in HIV-1 infection, treatment and vaccine trial outcomes. Importantly, we highlight contrasting findings that may be due to multiple factors and the relatively limited data from African populations. We recommend further studies especially in sub-Saharan Africa to confirm the role of FcγRIIa in the establishment of latent reservoir and to determine their influence in therapies involving bNAbs

COVID-19 pandemic: ten research questions Africa must answer for itself

The COVID-19 pandemic is spreading through Africa and governments are making frantic efforts to control spread, hospitalizations and deaths. While control measures are being taken, research into the biomedical and socio-cultural aspects of the pandemic, relevant to the African population, should not be ignored. It should not be assumed that research performed in Asian, American and European populations will always be applicable to Africa. Rather, research should be done in Africa to answer questions peculiar to the epidemic on the continent and help inform international guidelines. National guidelines for treatment and prevention, patient recoveries and discharge, and public health control measures should be based on research performed in the appropriate context for them to be effective and robust. Urgent research is needed in viral immunology and shedding, treatment and prevention trials, protection of healthcare personnel, and antimicrobial use among others. In this article, we propose ten research questions that when answered in a timely manner by scientists in Africa, will enhance Africa’s response to the pandemic

HIV cure strategies: Which ones are appropriate for Africa?

Although combination antiretroviral therapy (ART) has reduced mortality and improved lifespan for people living with HIV, it does not provide a cure. Patients must be on ART for the rest of their lives and contend with side effects, unsustainable costs, and the development of drug resistance. A cure for HIV is, therefore, warranted to avoid the limitations of the current therapy and restore full health. However, this cure is difficult to find due to the persistence of latently infected HIV cellular reservoirs during suppressive ART. Approaches to HIV cure being investigated include boosting the host immune system, genetic approaches to disable co-receptors and the viral genome, purging cells harboring latent HIV with latency-reversing latency agents (LRAs) (shock and kill), intensifying ART as a cure, preventing replication of latent proviruses (block and lock) and boosting T cell turnover to reduce HIV-1 reservoirs (rinse and replace). Since most people living with HIV are in Africa, methods being developed for a cure must be amenable to clinical trials and deployment on the continent. This review discusses the current approaches to HIV cure and comments on their appropriateness for Africa

The economic burden of cardiovascular disease and hypertension in low- and middle-income countries: a systematic review.

BACKGROUND: The evidence on the economic burden of cardiovascular disease (CVD) in low- and middle- income countries (LMICs) remains scarce. We conducted a comprehensive systematic review to establish the magnitude and knowledge gaps in relation to the economic burden of CVD and hypertension on households, health systems and the society. METHODS: We included studies using primary or secondary data to produce original economic estimates of the impact of CVD. We searched sixteen electronic databases from 1990 onwards without language restrictions. We appraised the quality of included studies using a seven-question assessment tool. RESULTS: Eighty-three studies met the inclusion criteria, most of which were single centre retrospective cost studies conducted in secondary care settings. Studies in China, Brazil, India and Mexico contributed together 50% of the total number of economic estimates identified. The quality of the included studies was generally low. Reporting transparency, particularly for cost data sources and results, was poor. The costs per episode for hypertension and generic CVD were fairly homogeneous across studies; ranging between $500 and$1500. In contrast, for coronary heart disease (CHD) and stroke cost estimates were generally higher and more heterogeneous, with several estimates in excess of $5000 per episode. The economic perspective and scope of the study appeared to impact cost estimates for hypertension and generic CVD considerably less than estimates for stroke and CHD. Most studies reported monthly costs for hypertension treatment around$22. Average monthly treatment costs for stroke and CHD ranged between $300 and$1000, however variability across estimates was high. In most LMICs both the annual cost of care and the cost of an acute episode exceed many times the total health expenditure per capita. CONCLUSIONS: The existing evidence on the economic burden of CVD in LMICs does not appear aligned with policy priorities in terms of research volume, pathologies studied and methodological quality. Not only is more economic research needed to fill the existing gaps, but research quality needs to be drastically improved. More broadly, national-level studies with appropriate sample sizes and adequate incorporation of indirect costs need to replace small-scale, institutional, retrospective cost studies

Barriers and facilitators to the implementation of a community-based hypertension improvement project in Ghana: a qualitative study of ComHIP.

BACKGROUND: Globally, hypertension is a leading cause of cardiovascular disease and mortality, with the majority of deaths occurring in low- and middle-income countries. Because the burden of hypertension is increasing in low resource settings with restricted infrastructure, it is imperative that new models for hypertension care are realised. One such model is the Community-based Hypertension Improvement Project (ComHIP) which employs a community-based method of task-shifting for managing hypertension. This study is a qualitative analysis of the barriers and facilitators of the main components of ComHIP. METHODS: We purposively selected 55 informants for semi-structured interviews or focus group discussions, which were carried out bythree trained local researchers in Krobo, Twi or English. Informants included patients enrolled in ComHIP, health care providers and Licensed Chemical Sellers trained by ComHIP, and Ghana Health Service employees. Data were analysed using a multi-step thematic analysis. RESULTS: While results of the effectiveness of the intervention are pending, overall, patients and nurses reported positive experiences within ComHIP, and found that it helped enable them to manage their hypertension. Healthcare providers appreciated the additional training, but had some gaps in their knowledge. Ghana Health Service employees were cautiously optimistic about the programme, but expressed some worries about the sustainability of the programme. Many informants expressed concerns over the inability of community nurses and workers to dispense anti-hypertensives, due to legal restrictions. CONCLUSIONS: The WHO recommends task-sharing as a technique for managing chronic conditions such as hypertension in resource constrained settings. ComHIP presents an example of a task-sharing programme with a high level of acceptability to all participants. Going forward, we recommend greater levels of communication and dialogue to allow community-based health workers to be allowed to dispense anti-hypertensives

Healthcare provider perspectives on HIV cure research in Ghana

INTRODUCTION: Antiretroviral therapy (ART) has reduced mortality and improved life expectancy among HIV patients but does not provide a cure. Patients must remain on lifelong medications and deal with drug resistance and side effects. This underscores the need for HIV cure research. However, participation in HIV cure research has risks without guaranteed benefits. We determined what HIV healthcare providers know about HIV cure research trials, the risks involved, and what kind of cure interventions they are likely to recommend for their patients. METHODS: We conducted in-depth qualitative interviews with 39 HIV care providers consisting of 12 physicians, 8 counsellors, 14 nurses, 2 pharmacists, 2 laboratory scientists, and 1 community advocate from three hospitals. Interviews were transcribed verbatim and coded, and thematic analysis was performed independently by two investigators. RESULTS: Participants were happy about the success of current treatments and hopeful that an HIV cure will be found in the near future, just as ART was discovered through research. They described cure as total eradication of the virus from the body and inability to test positive for HIV or transmit the virus. In terms of risk tolerance, respondents would recommend to their patients\u27 studies with mild to moderate risks like what patients on antiretroviral therapy experience. Participants were reluctant to recommend treatment interruption to patients as part of a cure study and wished trials could be performed without stopping treatment. Healthcare providers categorically rejected death or permanent disability as an acceptable risk. The possibility of finding a cure that will benefit the individual or future generations was strong motivations for providers to recommend cure trials to their patients, as was transparency and adequate information on proposed trials. Overall, the participants were not actively seeking knowledge on cure research and lacked information on the various cure modalities under investigation. CONCLUSION: While hopeful for an HIV cure, healthcare providers in Ghana expect a cure to be definitive and pose minimal risk to their patients

Health system challenges to hypertension and related non-communicable diseases prevention and treatment: perspectives from Ghanaian stakeholders.

BACKGROUND: Hypertension, itself a cardiovascular condition, is a significant risk factor for other cardiovascular diseases. Hypertension is recognized as a major public health challenge in Ghana. Beginning in 2014, a collaborative team launched the community-based hypertension improvement program (ComHIP) in one health district in Ghana. The ComHIP project, a public-private partnership, tests a community-based model that engages the private sector and utilizes information and communication technology (ICT) to control hypertension. This paper, focuses on the various challenges associated with managing hypertension in Ghana, as reported by ComHIP stakeholders. METHODS: A total of 55 informants - comprising patients, health care professionals, licensed chemical sellers (LCS), national and sub-national policymakers - were purposively selected for interview and focus group discussions (FGDs). Interviews were audio-recorded and transcribed verbatim. Where applicable, transcriptions were translated directly from local language to English. The data were then analysed using two-step thematic analysis. The protocol was approved by the two ethics review committees based in Ghana and the third, based in the United Kingdom. All participants were interviewed after giving informed consent. RESULTS: Our data have implications for the on-going implementation of ComHIP, especially the importance of policy maker buy-in, and the benefits, as well as drawbacks, of the program to different stakeholders. While our data show that the ComHIP initiative is acceptable to patients and healthcare providers - increasing providers' knowledge on hypertension and patients' awareness of same- there were implementation challenges identified by both patients and providers. Policy level challenges relate to task-sharing bottlenecks, which precluded nurses from prescribing or dispensing antihypertensives, and LCS from stocking same. Medication adherence and the phenomenon of medical pluralism in Ghana were identified challenges. The perspectives from the national level stakeholders enable elucidation of whole of health system challenges to ComHIP and similarly designed programmes. CONCLUSIONS: This paper sheds important light on the patient/individual, and system level challenges to hypertension and related non-communicable disease prevention and treatment in Ghana. The data show that although the ComHIP initiative is acceptable to patients and healthcare providers, policy level task-sharing bottlenecks preclude optimal implementation of ComHIP

Data management during COVID-19 outbreak response in Ghana: a reference laboratory perspective on key issues and measures

The COVID-19 pandemic caused by SARS-CoV-2 is an important subject for global health. Ghana experienced lowmoderate transmission of the disease when the first case was detected in March 12, 2020 until the middle of July when the number of cases begun to drop. By August 24, 2020, the country's total number of confirmed cases stood at 43,622, with 263 deaths. By the same time, the Noguchi Memorial Institute for Medical Research (NMIMR) of the University of Ghana, the primary testing centre for COVID-19, had tested 285,501 with 28,878 confirmed cases. Due to database gaps, there were initial challenges with timely reporting and feedback to stakeholders during the peak surveillance period. The gaps resulted from mismatches between samples and their accompanying case investigation forms, samples without case investigation forms and vice versa, huge data entry requirements, and delayed test results. However, a revamp in data management procedures, and systems helped to improve the turnaround time for reporting results to all interested parties and partners. Additionally, inconsistencies such as multiple entries and discrepant patient-sample information were resolved by introducing a barcoding electronic capture system. Here, we describe the main challenges with COVID-19 data management and analysis in the laboratory and recommend measures for improvement

Unwillingness of patients in Ghana to interrupt antiretroviral therapy for HIV cure research

OBJECTIVES: Though antiretroviral therapy (ART) has reduced HIV infection into a manageable chronic disease, it does not provide for a cure. HIV cure trials may carry risks for patients who are generally doing well on ART, making it imperative that their input is sought as various types of cure methods and trials are designed. Few studies have sought the views of African patients on HIV cure studies. The objective of this study was to determine the views and preferences of people living with HIV (PLWH) in Ghana on cure research. METHODS: We used a questionnaire to interview 251 PLWH in Ghana about their willingness to engage in HIV cure research. We investigated their motivations, the types of cure they would prefer and which risks were acceptable to them. RESULTS: Most participants were enthusiastic about participating in cure research and driven by both altruistic and personal motives. Patients preferred a cure where they would continue follow-up with their doctor (88%) compared to being assured that they have been completely cured and did not need further follow-up (11%). The vast majority of the respondents were risk averse. Most patients (67%) would decline to interrupt ART as part of a protocol for HIV cure research. In bivariate analysis, participants above the age of 40 years were more likely to agree to treatment interruption during cure studies (OR 2.77; 95% CI 1.21-.6.34. CONCLUSIONS: Our results show that preferred cure modalities and risk tolerance for patients in Africa may be different from those of other parts of the world. Extensive social science and behavioural studies are needed on the continent to help inform future cure trials