Therapeutic efficacy of generic artemether-lumefantrine in the treatment of uncomplicated malaria in Ghana: assessing anti-malarial efficacy amidst pharmacogenetic variations.

BACKGROUND: Despite efforts made to reduce morbidity and mortality associated with malaria, especially in sub-Saharan Africa, malaria continues to be a public health concern that requires innovative efforts to reach the WHO-set zero malaria agenda. Among the innovations is the use of artemisinin-based combination therapy (ACT) that is effective against Plasmodium falciparum. Generic artemether-lumefantrine (AL) is used to treat uncomplicated malaria after appropriate diagnosis. AL is metabolized by the cytochrome P450 family of enzymes, such as CYP2B6, CYP3A4 and CYP3A5, which can be under pharmacogenetic influence. Pharmacogenetics affecting AL metabolism, significantly influence the overall anti-malarial activity leading to variable therapeutic efficacy. This study focused on generic AL drugs used in malarial treatment as prescribed at health facilities and evaluated pharmacogenomic influences on their efficacy. METHODS: Patients who have been diagnosed with malaria and confirmed through RDT and microscopy were recruited in this study. Blood samples were taken on days 1, 2, 3 and 7 for parasite count and blood levels of lumefantrine, artemisinin, desbutyl-lumefantrine (DBL), and dihydroartemisinin (DHA), the active metabolites of lumefantrine and artemether, respectively, were analysed using established methods. Pharmacogene variation analysis was undertaken using iPLEX microarray and PCR-RFLP. RESULTS: A total of 52 patients completed the study. Median parasite density from day 1 to 7 ranged from 0-2666/µL of blood, with days 3 and 7 recording 0 parasite density. Highest median plasma concentration for lumefantrine and desbutyl lumefantrine, which are the long-acting components of artemisinin-based combinations, was 4123.75 ng/mL and 35.87 ng/mL, respectively. Day 7 plasma lumefantrine concentration across all generic ACT brands was ≥ 200 ng/mL which potentially accounted for the parasitaemia profile observed. Monomorphism was observed for CYP3A4 variants, while there were observed variations in CYP2B6 and CYP3A5 alleles. Among the CYP3A5 genotypes, significant differences in genotypes and plasma concentration for DBL were seen on day 3 between 1/*1 versus *1/*6 (p = 0.002), *1/*3 versus *1/*6 (p = 0.006) and *1/*7 versus *1/*6 (p = 0.008). Day 7 plasma DBL concentrations showed a significant difference between *1/*6 and *1/*3 (p = 0.026) expressors. CONCLUSIONS: The study findings show that CYP2B6 and CYP3A5 pharmacogenetic variations may lead to higher plasma exposure of AL metabolites.

A macrophage-cell model of HIV latency reveals the unusual importance of the bromodomain axis.

BACKGROUND: Although macrophages are now recognized as an essential part of the HIV latent reservoir, whether and how viral latency is established and reactivated in these cell types is poorly understood. To understand the fundamental mechanisms of viral latency in macrophages, there is an urgent need to develop latency models amenable to genetic manipulations and screening for appropriate latency-reversing agents (LRAs). Given that differentiated THP-1 cells resemble monocyte-derived macrophages in HIV replication mechanisms, we set out to establish a macrophage cell model for HIV latency using THP-1 cells. METHODS: We created single-cell clones of THP-1 cells infected with a single copy of the dual-labeled HIVGKO in which a codon switched eGFP (csGFP) is under the control of the HIV-1 5' LTR promoter, and a monomeric Kusabira orange 2 (mKO2) under the control of cellular elongation factor one alpha promoter (EF1α). Latently infected cells are csGFP-, mKO2+, while cells with actively replicating HIV (or reactivated virus) are csGFP+,mKO2+. After sorting for latently infected cells, each of the THP-1 clones with unique integration sites for HIV was differentiated into macrophage-like cells with phorbol 12-myristate 13-acetate (PMA) and treated with established LRAs to stimulate HIV reactivation. Monocyte-derived macrophages (MDMs) harboring single copies of HIVGKO were used to confirm our findings. RESULTS: We obtained clones of THP-1 cells with latently infected HIV with unique integration sites. When the differentiated THP-1 or primary MDMs cells were treated with various LRAs, the bromodomain inhibitors JQ1 and I-BET151 were the most potent compounds. Knockdown of BRD4, the target of JQ1, resulted in increased reactivation, thus confirming the pharmacological effect. The DYRK1A inhibitor Harmine and lipopolysaccharide (LPS) also showed significant reactivation across all three MDM donors. Remarkably, LRAs like PMA/ionomycin, bryostatin-1, and histone deacetylase inhibitors known to potently reactivate latent HIV in CD4 + T cells showed little activity in macrophages. CONCLUSIONS: Our results indicate that this model could be used to screen for appropriate LRAs for macrophages and show that HIV latency and reactivation mechanisms in macrophages may be distinct from those of CD4 + T cells.

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' 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.

Apolipoprotein E genetic variation, atherogenic index and cardiovascular disease risk assessment in an African population: An analysis of HIV and malaria patients in Ghana.

BACKGROUND: Apolipoprotein E is involved in lipid transport and clearance of lipoprotein through low-density lipoprotein receptors (LDLR). ApoE variation has been linked to cardiovascular disease (CVD) risk. There are 3 isoforms of ApoE which originate from two non-synonymous single nucleotide polymorphisms denoted as ε2, ε3 and ε4. The ε2 isoform is implicated in higher levels of atherogenic lipoprotein with the ε4 isoform causing LDLR downregulation. This leads to variable effects and differential CVD risk. Malaria and HIV are life-threatening diseases affecting several countries globally especially in sub-Saharan Africa. Parasite and viral activities have been implicated in lipid dysregulation leading to dyslipidaemia. This study examined ApoE variation and CVD risk assessment in malaria and HIV patients. METHODS: We compared 76 malaria-only, 33 malaria-HIV coinfected, 21-HIV-only and 31 controls from a tertiary health facility in Ghana. Fasting venous blood samples were taken for ApoE genotyping and lipid measurements. Clinical and laboratory data were collected with ApoE genotyping performed using Iplex Gold microarray and PCR-RFLP. Cardiovascular disease risk was calculated using the Framingham BMI and cholesterol risk and Qrisk3 tools. RESULTS: The frequency of C/C genotype for rs429358 was 9.32%, whiles T/T genotype for rs7412 was found in 2.48% of all participants. ε3/ε3 was the most distributed ApoE genotype accounting for 51.55% of the total participants whiles ε2/ε2 was found in 2.48% of participants, with 1 in malaria-only and 3 in HIV-only patients. There was a significant association between ε4+ and high TG (OR = 0.20, CI; 0.05-0.73; p = 0.015), whiles ε2+ was significantly associated with higher BMI (OR; 0.24, CI; 0.06-0.87; p = 0.030) and higher Castelli Risk Index II in females (OR = 11.26, CI; 1.37-92.30; p = 0.024). A higher proportion of malaria-only participants had a moderate to high 10-year CVD risk. CONCLUSION: Overall malaria patients seem to have a higher CVD risk though the means through which this occurs may be poorly understood. ε2/ε2 genotypes was observed in our population at a lower frequency. Further studies are vital to determine CVD risk in malaria and how this occurs.

Network modeling suggests HIV infection phenocopies PI3K-AKT pathway mutations to enhance HPV-associated cervical cancer.

Women coinfected with human immunodeficiency virus type 1 (HIV-1) and human papillomavirus (HPV) are six times as likely to develop invasive cervical carcinoma compared to those without HIV. Unlike other HIV-associated cancers, the risk of cervical cancer development does not change when HPV/HIV coinfected women begin antiretroviral therapy, suggesting HIV-associated immune suppression is not a key driver of cervical cancer development in coinfected women. Here, we investigated whether the persistent secretion of inflammatory factors in HIV-positive patients on antiretroviral therapy could enhance cancer signaling in HPV-infected cervical cells via endocrine mechanisms. We integrated previously reported HIV-induced secreted inflammatory factors (Hi-SIFs), HIV and HPV virus-human protein interactions, and cervical cancer patient genomic data using network propagation to understand the pathways underlying disease development in HPV/HIV coinfection. Our results pinpointed the PI3K-AKT signaling pathway to be enriched at the interface between Hi-SIFs and HPV-host molecular networks, in alignment with PI3K pathway mutations being prominent drivers of HPV-associated, but HIV independent, cervical cancer development. Furthermore, we experimentally stimulated cervical cells with 14 Hi-SIFs to assess their ability to activate PI3K-AKT signaling. Strikingly, we found 8 factors (CD14, CXCL11, CXCL9, CXCL13, CXCL17, AHSG, CCL18, and MMP-1) to significantly upregulate AKT phosphorylation (pAKT-S473) relative to a phosphate buffered saline control. Our findings suggest that Hi-SIFs cooperate with HPV infection in cervical cells to over-activate PI3K-AKT signaling, effectively phenocopying PI3K-AKT pathway mutations, resulting in enhanced cervical cancer development in coinfected women. Our insights could support the design of therapeutic interventions targeting the PI3K-AKT pathway or neutralizing Hi-SIFs in HPV/HIV coinfected cervical cancer patients.

Psychometric assessment of HIV stigma in patients attending a tertiary facility: An initial validation of the Berger HIV stigma scale in a Ghanaian perspective.

BACKGROUND: HIV-related stigma and discrimination are major challenges to people living with HIV (PLWHIV) and are due to misconceptions. Due to socioeconomic variations, there is increased stigma experienced by PLWHIV in sub-Saharan Africa (SSA). Stigma affects adherence to antiretroviral medications by PLWHIV and defeats the goal of achieving viral suppression. This study evaluated the Bergers HIV stigma scale in PLWHIV in Ghana regarding construct validity and reliability and assessed which aspect of stigma is critical for immediate redress. METHODS: The Berger et al. HIV stigma scale (39 items) and some selected questions from HIV stigma and discrimination measurement tool of the International Centre for Research on Women, Washington, DC were administered to a cohort of PLWHIV in Ghana (n = 160). Clinico- demographic data was collected from their folders and verbally. The psychometric assessment included exploratory factor analysis whiles scale reliability was evaluated as internal consistency by calculating Cronbach's α. RESULTS: The exploratory factor analysis suggested a four-factor solution which is like the original Berger HIV scale with sub-scales personalised stigma, disclosure concerns, negative self- image, and concerns with public attitudes. Items in the sub-scales personalised stigma (15- items), disclosure concerns (6), negative self-image (7) and concerns with public attitudes (6) were reduced compared to the original scale. Cronbach's α for the overall HIV stigma scale (34-items) was 0.808 whiles the sub-scales α ranged from 0.77 to 0.89. Analysis suggested the prevalence of a fundamental one-dimensional factor solution which yielded a 34-item scale after removing items for low factor loadings. Disclosure concerns was the highest ranked subscale although our study also found that about 65% of PLWHIV among our study participants had disclosed their status. CONCLUSION: Our 34-item abridged Berger HIV stigma scale showed sufficient reliability with high Cronbach's α and construct validity. Disclosure concerns ranked high among the sub-scales on the scale. Exploring specific interventions and strategies to address stigma concerns in our population will aid in the reduction of HIV-related stigma and associated consequences.

SARS-CoV-2 Molecular Evolutionary Dynamics in the Greater Accra Region, Ghana.

To assess dynamics of SARS-CoV-2 in Greater Accra Region, Ghana, we analyzed SARS-CoV-2 genomic sequences from persons in the community and returning from international travel. The Accra Metropolitan District was a major origin of virus spread to other districts and should be a primary focus for interventions against future infectious disease outbreaks.

HIV cure: an acceptability scientific agenda.

PURPOSE OF REVIEW: Recent years have seen major investments into HIV cure research, seeking a permanent cure or remission. The purpose of this review is to consider how this important research agenda could be broadened to include issues of acceptability and appropriateness for different populations. RECENT FINDINGS: We discuss how the definitions of cure such as functional cure (remission) or complete cure (viral elimination) could be interpreted differently by various populations. We also discuss the different methods of cure and the importance of including Africa in cure research to ensure that emerging remedies could be trialled and utilized on the continent that bears the brunt of the AIDS pandemic. SUMMARY: We propose that the social science research of HIV cure acceptability should be done concurrently with the basic and clinical sciences, to ensure that cure methods consider stakeholder preferences.

Delayed SARS-COV-2 clearance in infected persons in Ghana.

Objective: This study aimed to determine the duration of SARS-CoV-2 clearance in persons in Ghana. The research question was whether the duration of virus clearance in Ghana matched the 14 days recommended by the World Health Organization (WHO); this had direct implications for transmission, which was key in managing the COVID-19 pandemic. Design: This was a retrospective analytical study. Setting: All facilities that submitted clinical specimens to Noguchi Memorial Institute for Medical Research (NMIMR) for SARS-CoV-2 diagnosis between March to June 2020 were included in the study. Interventions: Samples from 480 persons who tested positive for SARS-CoV-2 by RT-PCR from March to June 2020 at NMIMR and submitted at least two follow-up samples were retrospectively analysed. Individuals with two consecutive negative RT-PCR retesting results were considered to have cleared SARS-CoV-2. Results: The median time from the initial positive test to virus clearance was 20 days (IQR: 5-56 days). This was six days longer than the WHO-recommended 14 days, after which infected persons could be de-isolated. Sputum and nasopharyngeal swabs proved more sensitive for detecting viral RNA as the infection progressed. At a significance level of 0.05, age and sex did not seem to influence the time to SARS-CoV-2 clearance. Conclusions: The median time to SARS-CoV-2 clearance in this study was 20 days, suggesting that SARS-CoV-2 infected persons in Ghana take longer to clear the virus. This finding calls for further investigations into whether patients who remain PCR positive continue to be infectious and inform isolation practices in Ghana. Funding: The study was supported by the Ministry of Health/ Ghana Health Service through the provision of laboratory supplies, the US Naval Medical Research Unit #3, the World Health Organization, the Jack Ma Foundation and the Virology Department of Noguchi Memorial Institute for Medical Research, University of Ghana. Research projects within Noguchi Memorial Institute for Medical Research contributed reagents and laboratory consumables. However, the authors alone are responsible for the contents of this manuscript.

Delayed SARS-COV-2 clearance in infected persons in Ghana

Objective: This study aimed to determine the duration of SARS-CoV-2 clearance in persons in Ghana. The research question was whether the duration of virus clearance in Ghana matched the 14 days recommended by the World Health Organization (WHO); this had direct implications for transmission, which was key in managing the COVID-19 pandemic. Design: This was a retrospective analytical study. Setting: All facilities that submitted clinical specimens to Noguchi Memorial Institute for Medical Research (NMIMR) for SARS-CoV-2 diagnosis between March to June 2020 were included in the study. Interventions: Samples from 480 persons who tested positive for SARS-CoV-2 by RT-PCR from March to June 2020 at NMIMR and submitted at least two follow-up samples were retrospectively analysed. Individuals with two consecutive negative RT-PCR retesting results were considered to have cleared SARS-CoV-2. Results: The median time from the initial positive test to virus clearance was 20 days (IQR: 5-56 days). This was six days longer than the WHO-recommended 14 days, after which infected persons could be de-isolated. Sputum and nasopharyngeal swabs proved more sensitive for detecting viral RNA as the infection progressed. At a significance level of 0.05, age and sex did not seem to influence the time to SARS-CoV-2 clearance. Conclusions: The median time to SARS-CoV-2 clearance in this study was 20 days, suggesting that SARS-CoV-2 infected persons in Ghana take longer to clear the virus. This finding calls for further investigations into whether patients who remain PCR positive continue to be infectious and inform isolation practices in Ghana.

Zero malaria: a mirage or reality for populations of sub-Saharan Africa in health transition.

The global burden of malaria continues to be a significant public health concern. Despite advances made in therapeutics for malaria, there continues to be high morbidity and mortality associated with this infectious disease. Sub-Saharan Africa continues to be the most affected by the disease, but unfortunately the region is burdened with indigent health systems. With the recent increase in lifestyle diseases, the region is currently in a health transition, complicating the situation by posing a double challenge to the already ailing health sector. In answer to the continuous challenge of malaria, the African Union has started a "zero malaria starts with me" campaign that seeks to personalize malaria prevention and bring it down to the grass-root level. This review discusses the contribution of sub-Saharan Africa, whose population is in a health transition, to malaria elimination. In addition, the review explores the challenges that health systems in these countries face, that may hinder the attainment of a zero-malaria goal.

Isoform-Selective Versus Nonselective Histone Deacetylase Inhibitors in HIV Latency Reversal.

HIV remains incurable due to the persistence of a latent viral reservoir found in HIV-infected cells, primarily resting memory CD4+ T cells. Depletion of this reservoir may be the only way to end this deadly epidemic. In latency, the integrated proviral DNA of HIV is transcriptionally silenced partly due to the activity of histone deacetylases (HDACs). One strategy proposed to overcome this challenge is the use of HDAC inhibitors (HDACis) as latency reversal agents to induce viral expression (shock) under the cover of antiretroviral therapy. It is hoped that this will lead to elimination of the reservoir by immunologic and viral cytopathic (kill). However, there are 18 isoforms of HDACs leading to varying selectivity for HDACis. In this study, we review HDACis with emphasis on their selectivity for HIV latency reversal.

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.

SARS-CoV-2 infections among asymptomatic individuals contributed to COVID-19 cases: A cross-sectional study among prospective air travelers from Ghana.

Background: The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by asymptomatic individuals has been reported since the early stages of the coronavirus disease 2019 (COVID-19) outbreak in various parts of the world. However, there are limited data regarding SARS-CoV-2 among asymptomatic individuals in Ghana. The aim of the study was to use test data of prospective travelers from Ghana as a proxy to estimate the contribution of asymptomatic cases to the spread of COVID-19. Methods: The study analyzed the SARS-CoV-2 PCR test data of clients whose purpose for testing was classified as "Travel" at the COVID-19 walk-in test center of the Noguchi Memorial Institute for Medical Research (NMIMR) from July 2020 to July 2021. These individuals requesting tests for travel generally had no clinical symptoms of COVID-19 at the time of testing. Data were processed and analyzed using Microsoft Excel office 16 and STATA version 16. Descriptive statistics were used to summarize data on test and demographic characteristics. Results: Out of 42,997 samples tested at the center within that period, 28,384 (66.0%) were classified as "Travel" tests. Of these, 1,900 (6.7%) tested positive for SARS-CoV-2. The majority (64.8%) of the "Travel" tests were requested by men. The men recorded a SARS-CoV-2 positivity of 6.9% compared to the 6.4% observed among women. Test requests for SARS-CoV-2 were received from all regions of Ghana, with a majority (83.3%) received from the Greater Accra Region. Although the Eastern region recorded the highest SARS-CoV-2 positivity rate of 8.35%, the Greater Accra region contributed 81% to the total number of SARS-CoV-2 positive cases detected within the period of study. Conclusion: Our study found substantial SARS-CoV-2 positivity among asymptomatic individuals who, without the requirement for a negative SARS-CoV-2 result for travel, would have no reason to test. These asymptomatic SARS-CoV-2-infected individuals could have traveled to other countries and unintentionally spread the virus. Our findings call for enhanced tracing and testing of asymptomatic contacts of individuals who tested positive for SARS-CoV-2.

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.

Undernutrition and HIV Infection in Sub-Saharan Africa: Health Outcomes and Therapeutic Interventions.

PURPOSE OF REVIEW: Sub-Saharan Africa (SSA) is disproportionately burdened by the twin epidemics of food insecurity and HIV infection, and protein-calorie undernutrition is common among persons with HIV (PWH) initiating antiretroviral therapy (ART) in the region. In this review, we discuss the intersection of HIV infection and undernutrition, health outcomes among undernourished PWH starting ART, and the demonstrated and potential benefits of therapeutic interventions such as micro/macronutrient supplementation and pharmacological agents. RECENT FINDINGS: A low body mass index (BMI), used as a general indicator of poor nutrition in most studies, is associated with impaired immune recovery and increased mortality in the early ART period. The increased risk of mortality is multifactorial, and contributors include undernutrition-related immune system dysfunction, increased susceptibility to opportunistic infections, and metabolic and cardiovascular dysregulation. Clinical trials of micro/macronutrient supplementary feeding, appetite stimulants (hormones and anabolic agents), and recombinant adipokines have shown a benefit for weight gain and metabolic health, but there are few data on mortality or immune recovery. A substantial proportion of PWH in SSA are undernourished, and undernutrition contributes to an increased risk of mortality and other adverse health outcomes. To date, there have been few prospective trials of nutritional supplementation and/or pharmacologic therapy among undernourished PWH in SSA, though findings from other settings suggest a potential benefit in this population.

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. p â€‹= â€‹0.0159). 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.

Genomic analysis of SARS-CoV-2 reveals local viral evolution in Ghana.

The confirmed case fatality rate for the coronavirus disease 2019 (COVID-19) in Ghana has dropped from a peak of 2% in March to be consistently below 1% since May 2020. Globally, case fatality rates have been linked to the strains/clades of circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within a specific country. Here we present 46 whole genomes of SARS-CoV-2 circulating in Ghana, from two separate sequencing batches: 15 isolates from the early epidemic (March 12-April 1 2020) and 31 from later time-points ( 25-27 May 2020). Sequencing was carried out on an Illumina MiSeq system following an amplicon-based enrichment for SARS-CoV-2 cDNA. After genome assembly and quality control processes, phylogenetic analysis showed that the first batch of 15 genomes clustered into five clades: 19A, 19B, 20A, 20B, and 20C, whereas the second batch of 31 genomes clustered to only three clades 19B, 20A, and 20B. The imported cases (6/46) mapped to circulating viruses in their countries of origin, namely, India, Hungary, Norway, the United Kingdom, and the United States of America. All genomes mapped to the original Wuhan strain with high similarity (99.5-99.8%). All imported strains mapped to the European superclade A, whereas 5/9 locally infected individuals harbored the B4 clade, from the East Asian superclade B. Ghana appears to have 19B and 20B as the two largest circulating clades based on our sequence analyses. In line with global reports, the D614G linked viruses seem to be predominating. Comparison of Ghanaian SARS-CoV-2 genomes with global genomes indicates that Ghanaian strains have not diverged significantly from circulating strains commonly imported into Africa. The low level of diversity in our genomes may indicate lower levels of transmission, even for D614G viruses, which is consistent with the relatively low levels of infection reported in Ghana.

SARS-CoV-2 detection among international air travellers to Ghana during mandatory quarantine.

OBJECTIVES: To determine the prevalence of SARS-CoV-2 detection among international travellers to Ghana during mandatory quarantine. DESIGN: A retrospective cross-sectional study. SETTING: Air travellers to Ghana on 21st and 22nd March 2020. PARTICIPANTS: On 21st and 22nd March 2020, a total of 1,030 returning international travellers were mandatorily quarantined in 15 different hotels in Accra and tested for SARS-CoV-2. All of these persons were included in the study. MAIN OUTCOME MEASURE: Positivity for SARS-CoV-2 by polymerase chain reaction. RESULTS: The initial testing at the beginning of quarantine found 79 (7.7%) individuals to be positive for SARS-CoV-2. In the exit screening after 12 to 13 days of quarantine, it was discovered that 26 of those who tested negative for SARS-CoV-2 in the initial screening subsequently tested positive. CONCLUSIONS: Ghana likely averted an early community spread of COVID-19 through the proactive approach to quarantine international travellers during the early phase of the pandemic. FUNDING: None.