HIV virological non-suppression and its associated factors in children on antiretroviral therapy at a major treatment centre in Southern Ghana: a cross-sectional study.

BACKGROUND: Children living with human immunodeficiency virus (HIV) infection require lifelong effective antiretroviral therapy (ART). The goal of ART in HIV-infected persons is sustained viral suppression. There is limited information on virological non-suppression or failure and its associated factors in children in resource limited countries, particularly Ghana. METHODS: A cross-sectional study of 250 children aged 8 months to 15 years who had been on ART for at least 6 months attending the Paediatric HIV clinic at Korle Bu Teaching hospital in Ghana was performed. Socio-demographic, clinical, laboratory and ART Adherence related data were collected using questionnaires as well as medical records review. Blood samples were obtained for viral load and CD4+ count determination. Viral load levels > 1000 copies/ml on ART was considered virological non-suppression. Logistic regression was used to identify factors associated with virological non-suppression. RESULTS: The mean (±SD) age of the study participants was 11.4 ± 2.4 years and the proportion of males was 53.2%. Of the 250 study participants, 96 (38.4%) had virological non-suppression. After adjustment for significant variables, the factors associated with non-suppressed viral load were female gender (AOR 2.51 [95% CI 1.04-6.07], p = 0.041), having a previous history of treatment of tuberculosis (AOR 4.95 [95% CI 1.58-15.5], p = 0.006), severe CD4 immune suppression status at study recruitment (AOR 24.93 [95% CI 4.92-126.31], p < 0.001) and being on a nevirapine (NVP) based regimen (AOR 7.93 [95% CI 1.58-1.15], p = 0.005). CONCLUSION: The prevelance of virological non-suppression was high. Virological non-suppression was associated with a previous history of TB treatment, female gender, severe CD4 immune suppression status at study recruitment and being on a NVP based regimen. Early initiation of ART and phasing out NVP-based regimen might improve viral load suppression in children. In addition, children with a history of TB may need focused measures to maximize virological suppression.

COVID-19 in patients presenting with malaria-like symptoms at a primary healthcare facility in Accra, Ghana.

BACKGROUND: Malaria is a common and severe public health problem in Ghana and largely responsible for febrile symptoms presented at health facilities in the country. Other infectious diseases, including COVID-19, may mimic malaria due to their shared non-specific symptoms such as fever and headache thus leading to misdiagnosis. This study therefore investigated COVID-19 among patients presenting with malaria-like symptoms at Korle-Bu Polyclinic, Accra, Ghana. METHODS: This study enrolled 300 patients presenting with malaria-like symptoms aged ≥18yrs. After consent was obtained from study patients, two to three millilitres of whole blood, nasopharyngeal and oropharyngeal swab samples, were collected for screening of Plasmodium falciparum using malaria rapid diagnostic test, microscopy and nested PCR, and SARS-CoV-2 using SARS-CoV-2 antigen test and Real-time PCR, respectively. The plasma and whole blood were also used for COVID-19 antibody testing and full blood counts using hematological analyser. SARS-CoV-2 whole genome sequencing was performed using MinIon sequencing. RESULTS: The prevalence of malaria by microscopy, RDT and nested PCR were 2.3%, 2.3% and 2.7% respectively. The detection of SARS-CoV-2 by COVID-19 Rapid Antigen Test and Real-time PCR were 8.7% and 20% respectively. The Delta variant was reported in 23 of 25 SARS-CoV-2 positives with CT values below 30. Headache was the most common symptom presented by study participants (95%). Comorbidities reported were hypertension, asthma and diabetes. One hundred and thirteen (37.8%) of the study participants had prior exposure to SARS CoV-2 and (34/51) 66.7% of Astrazeneca vaccinated patients had no IgG antibody. CONCLUSION: It may be difficult to use clinical characteristics to distinguish between patients with COVID-19 having malaria-like symptoms. Detection of IgM using RDTs may be useful in predicting CT values for SARS-CoV-2 real-time PCR and therefore transmission.

Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana.

BACKGROUND: Antiretroviral therapy (ART) scale-up in resource-limited countries, with limited capacity for CD4 and HIV viral load monitoring, presents a unique challenge. We determined the effectiveness of first-line ART in a real world pediatric HIV clinic and explored associations between readily obtainable patient data and the trajectories of change in CD4 count and HIV viral load. METHODS: We performed a longitudinal study of a cohort of HIV-infected children initiating ART at the Korle-Bu Teaching Hospital Pediatric HIV clinic in Accra, Ghana, aged 0-13 years from 2009-2012. CD4 and viral load testing were done every 4 to 6 months and genotypic resistance testing was performed for children failing therapy. A mixed linear modeling approach, combining fixed and random subject effects, was employed for data analysis. RESULTS: Ninety HIV-infected children aged 0 to 13 years initiating ART were enrolled. The effectiveness of first-line regimen among study participants was 83.3%, based on WHO criteria for virologic failure. Fifteen of the 90 (16.7%) children met the criteria for virologic treatment failure after at least 24 weeks on ART. Sixty-seven percent virologic failures harbored viruses with ≥ 1 drug resistant mutations (DRMs); M184V/K103N was the predominant resistance pathway. Age at initiation of therapy, child's gender, having a parent as a primary care giver, severity of illness, and type of regimen were associated with treatment outcomes. CONCLUSIONS: First-line ART regimens were effective and well tolerated. We identified predictors of the trajectories of change in CD4 and viral load to inform targeted laboratory monitoring of ART among HIV-infected children in resource-limited countries.

Hepatitis B and human immunodeficiency virus infections within correctional facilities in Ghana.

Previous studies have suggested high Immunodeficiency Virus (HIV) and hepatitis B virus (HBV) prevalence in prisons in Ghana. However, this study was part of a nationally representative bio-behavioural survey and determined the prevalence of HIV and HBV among prison inmates and identified factors associated with these infections. Both biomedical and behavioural data were collected from a total of 2,443 prison inmates from 19 prison stations during 2013 in Ghana; 12 male prisons and 7 female prisons selected across the country. The national HIV screening algorithm was used for HIV testing while two rapid detection tests were used to confirm HBV infections. HIV and HBV prevalence among prisoners in Ghana were approximately 2.34% and 12.38% respectively. Only 5 inmates, had co-infection with both viruses. The prevalence of HIV was significantly lower among male inmates (1.5%) compared to the female inmates (11.8%). Age, sex, and marital status, were significantly associated with both HIV and HBV infections. However, BMI category, IDU, and time spent in prison were associated with HIV infections. The educational level was significantly associated with HBV infections. After binary logistic regression, being female (AOR: 0.18, 95% CI: 0.07-0.45, p<0.001) and having a stay of 5 years or more (AOR: 0.07, 95% CI: 0.01-0.60, p = 0.016), increased the risk of having HIV infection. While, those with no formal education (AOR: 0.65, 95% CI: 0.45-0.95, p = 0.024) and are underweight (AOR: 0.51, 95% CI: 0.27-0.99, p = 0.046), were more likely to have HBV infection. Forced penetrative sex may be a problem in the prisons. The need to have and strengthen an integrated screening, treatment and vaccination plan for the prison is emphasized. The prison does not serve as an exceptionally high risk to the general population. The findings support a critical look at the issue of forced penetrative sex in the prisons.

Web interface-supported transmission risk assessment and cost-effectiveness analysis of postdonation screening: a global model applied to Ghana, Thailand, and the Netherlands.

BACKGROUND: The goal of our research was to actively involve decision makers in the economic assessment of screening strategies in their region. This study attempted to accomplish this by providing an easy-to-use Web interface at http://www.bloodsafety.info that allows decision makers to adapt this model to local conditions. STUDY DESIGN AND METHODS: The cost-effectiveness was compared of 1) adding antigen screening to antibody screening for hepatitis C virus (HCV) and human immunodeficiency virus (HIV); 2) adding nucleic acid amplification testing (NAT) on hepatitis B virus (HBV), HCV, and HIV in minipool (pool of 6 [MP6] and 24 [MP24]) to antibody screening and hepatitis B surface antigen (HBsAg) screening; and 3) individual-donation NAT on HBV, HCV, and HIV to antibody screening and HBsAg screening for Ghana, Thailand, and the Netherlands. RESULTS: The combination of HCV antibody-antigen combination (combo) and HIV combo added to antibody screening in Ghana and Thailand was cost-effective according to the WHO criteria. MP24-NAT screening in Ghana was also cost-effective. MP24-NAT on HBV, HCV, and HIV was not cost-effective compared to the other screening strategies evaluated for the Netherlands. Large regional differences in cost-effectiveness were found for Thailand. CONCLUSION: The young transfusion recipient population of Ghana in combination with a high risk of viral transmission yields better cost-effectiveness for additional tests. The advanced age of the transfused population of the Netherlands and a small risk of viral transmission gives poor cost-effectiveness for more sensitive screening techniques. It was demonstrated that a global health economic model combined with a Web interface can provide easy access to risk assessment and cost-effectiveness analysis.

Drug resistance mutations and viral load in human immunodeficiency virus type 2 and dual HIV-1/HIV-2 infected patients in Ghana.

Antiretroviral therapy (ART) and drug resistance studies worldwide have focused almost exclusively on human immunodeficiency virus type 1 (HIV-1). As a result, there is limited information on ART and drug resistance in HIV-2 patients. In Ghana, the HIV epidemic is characterized by the domination of HIV-1, with cocirculating HIV-2. We, therefore, sought to determine viral load and drug resistance mutations in HIV-2 patients to inform the clinical management of such individuals in Ghana.We used purposive sampling to collect blood from 16 consented patients, confirmed as HIV-2 or HIV-1/2 dual infections by serology. A 2-step real-time RT-PCR assay was used to determine plasma HIV-2 RNA viral loads. For drug resistance testing, nucleic acids were extracted from plasma and peripheral blood mononuclear cells. The reverse transcriptase and protease genes of HIV-2 were amplified, sequenced and analyzed for drug resistance mutations and HIV-2 group.HIV-2 viral load was detected in 9 of 16 patients. Six of these had quantifiable viral loads (range: 2.62-5.45 log IU/mL) while 3 had viral loads below the limit of quantification. Sequences were generated from 7 out of 16 samples. Five of these were classified as HIV-2 group B and 2 as HIV-2 group A. HIV-2 drug resistance mutations (M184V, K65R, Y115F) were identified in 1 patient.This study is the first to report HIV-2 viral load and drug resistance mutations in HIV-2 strains from Ghana. The results indicate the need for continuous monitoring of drug resistance among HIV-2- infected patients to improve their clinical management.

Cost-effectiveness of HIV screening of blood donations in Accra (Ghana).

OBJECTIVES: Areas with high HIV-incidence rates compared to the developed world may benefit from additional testing in blood banks and may show more favorable cost-effectiveness ratios. We evaluated the cost-effectiveness of adding p24 antigen, mini pool nucleic acid amplification testing (MP-NAT), or individual donation NAT (ID-NAT) to the HIV-antibody screening at the Korle Bu Teaching Hospital (Accra, Ghana), where currently only HIV-antibody screening is undertaken. METHODS: The residual risk of HIV transmission was derived from blood donations to the blood bank of the Korle Bu Teaching Hospital in 2004. Remaining life expectancies of patients receiving blood transfusion were estimated using the World Health Organization life expectancies. Cost-effectiveness ratios for adding the tests to HIV-antibody screening only were determined using a decision tree model and a Markov model for HIV. RESULTS: The prevalence of HIV was estimated at 1.51% in 18,714 donations during 2004. The incremental cost per disability-adjusted life-year (DALY) averted was US$1237 for p24 antigen, US$3142 for MP-NAT and US$7695 compared to the next least expensive strategy. HIV-antibody screening itself was cost-saving compared to no screening at all, gaining US$73.85 and averting 0.86 DALY per transfused patient. Up to a willingness-to-pay of US$2736 per DALY averted, HIV-antibody screening without additional testing was the most cost-effective strategy. Over a willingness-to-pay of US$11,828 per DALY averted, ID-NAT was significantly more cost-effective than the other strategies. CONCLUSIONS: Adding p24 antigen, MP-NAT, or ID-NAT to the current antibody screening cannot be regarded as a cost-effective health-care intervention for Ghana.

Cost-effectiveness of antenatal HIV-testing: reviewing its pharmaceutical and methodological aspects.

This paper reviews the pharmacoeconomic aspects of antenatal testing for HIV. HIV is a retrovirus which is transmitted among humans through sexual contact, infected blood or blood products (needle sharing or percutaneous accidents) and from mother to child (vertical transmission). Vertical transmission from the HIV-infected mother can occur in utero during and after delivery, through breastfeeding. Effective interventions available to reduce the risk of vertical transmission include: pharmacotherapy prior, during and after delivery; voluntary caesarean section; and replacing breastfeeding by bottle-feeding [1,2]. The existence of these effective interventions underlies the need to detect yet undiagnosed HIV-infection in pregnancy through antenatal testing. Contemporary pharmacotherapy consists of a combination of three or more antiretroviral drugs, also referred to as highly-active antiretroviral therapy (HAART). For newly detected HIV-infected mothers, the Centers for Disease Control suggests the use of a zidovudine-comprising combination with one other nucleoside analogue reverse transcriptase inhibitor and a protease inhibitor (PI) [3]. As HIV in pregnancy may be asymptomatic, structured antenatal HIV-testing therefore seems to offer an attractive prevention strategy. Two broad types of approaches exist: selective or targeted testing versus universal testing. The availability of effective - but expensive - combination therapies since 1996 has greatly enhanced the importance of pharmacoeconomic assessments in the field of HIV-infection. Treatment of the mother will incur additional costs but will also make any programme more effective. Furthermore, avoiding children becoming infected with HIV will also incur monetary benefits, as children are also being treated with HAART. In summary, the background of antenatal HIV-testing has undergone major changes compared with the early 1990s. This review of the pharmacoeconomics of antenatal HIV-testing followed a systematic approach as it was performed according to prespecified criteria, allowing valid comparisons in methodologies and findings of those studies that have yet been conducted in this area.

Severe acute rotavirus gastroenteritis in children less than 5 years in southern Ghana: 2006-2011.

BACKGROUND: Rotavirus is a major cause of acute gastroenteritis (AGE) globally. Local data on disease burden will guide recommendations for rotavirus vaccination and monitoring impact of the intervention. METHODS: Prospective surveillance for rotavirus gastroenteritis was conducted in 3 hospitals in southern Ghana during the period August 2006 to December 2011, as part of the African Rotavirus Surveillance Network. Clinical data and stool specimens were collected from children <5 years of age and hospitalized with AGE (defined as 3 or more watery stools for up to 7 days). Stool was tested for rotavirus by enzyme immunoassay and rotavirus genotype identified by reverse-transcriptase polymerase chain reaction. RESULTS: We tested 3044 stool samples from 3939 children. Rotavirus was detected in 45.6%, 51.3% and 48.5% of cases at the primary, secondary and tertiary care hospital, respectively. Both genders were equally affected; 75% (2954/3939) of the cohort were aged 3-18 months. Overall, rotavirus was detected in 49.4% (1504/3044) of cases, caused over 30% of AGE hospitalizations all year round and up to 70% of cases during peak seasons. Peak season occurred during cool dry months in 2008, 2010 and 2011 and the rainy season in 2009. Mortality from AGE occurred in 1.5% (45/3044) of cases and 48.9% (22/45) of these were rotavirus positive. CONCLUSIONS: Rotavirus causes significant morbidity and mortality in young Ghanaian children. As Ghana introduced rotavirus vaccination in the national immunization program in 2012, continued surveillance is required to monitor the impact of this intervention.

Prevalence of severe acute rotavirus gastroenteritis and intussusceptions in Ghanaian children under 5 years of age.

INTRODUCTION: Vaccination is the most effective preventive strategy against rotavirus disease. Regional differences in prevalent rotavirus genotypes may affect vaccine efficacy. Pre-vaccine surveillance for burden of rotavirus disease, prevalent rotavirus genotypes, and association between rotavirus disease and intussusceptions helps in monitoring the impact of vaccination. METHODOLOGY: A prospective study was conducted from January 2008 to December 2009 in children younger than five years hospitalized for longer than 24 hours with acute gastroenteritis. Data on confirmed cases of intussusception were collected retrospectively. Stools were tested by enzyme immunoassay, reverse-transcriptase polymerase chain reaction and nucleotide sequencing.  RESULTS: Acute gastroenteritis (AGE) caused 13.1% (2,147/16,348) of hospitalizations among children under five years. Stools were tested for 50.2% (1077/2147) of AGE cases. Of these, 49% (528/1077) were rotavirus positive. Rotavirus gastroenteritis, non-rotavirus gastroenteritis, and intussusceptions were most prevalent in children under 15 months [80.3%, 74% and 91% respectively]. Rotavirus was detected from more than 60% of acute gastroenteritis cases during peak months. The prevalence of intussusception showed no seasonal pattern. The peak ages of six to twelve months for acute gastroenteritis and five to eight months for intussusception overlapped. G1, G2 and mixed G/P genotypes were common in the isolated rotaviruses. CONCLUSION: Rotavirus gastroenteritis causes significant morbidity in children younger than five years of age in Ghana. Although the peak age of rotavirus gastroenteritis and intussusceptions overlapped, there was no seasonal correlation between them. The high prevalence of mixed G/P genotypes in Ghanaian children may affect the effectiveness of vaccination.

CYP2B6, CYP2A6 and UGT2B7 genetic polymorphisms are predictors of efavirenz mid-dose concentration in HIV-infected patients.

OBJECTIVE: UDP-glucuronosyltransferase (UGT) 2B7 was recently identified as the main enzyme mediating efavirenz N-glucuronidation. In this study, we determined whether selected UGT2B7 polymorphisms could be used to enhance the prediction of efavirenz plasma concentrations from CYP2B6 and CYP2A6 genotypes. METHODS: Mid-dose efavirenz plasma concentrations were determined in 94 HIV-infected Ghanaian patients at 2-8 weeks of antiretroviral therapy. CYP2B6 and CYP2A6 genotypes had been previously reported. UGT2B7 exon 2 single-nucleotide polymorphisms (SNPs) c.735A>G (UGT2B7*1c; rs28365062) and c.802C>T (H268Y; UGT2B7*2; rs7439366) were determined by direct sequencing with UGT2B7*1a defined as the reference allele. Relationships between efavirenz plasma concentrations, demographic variables and genotypes were evaluated by univariate and multivariate statistical approaches. RESULTS: The mean (+/-SD) mid-dose efavirenz plasma concentration was 3218 (+/-3905) ng/ml with coefficient of variation of 121%. Independent predictors of efavirenz concentration included CYP2B6 c.516TT genotype (4030 ng/ml increase; 95% confidence interval 2882-5505 ng/ml, P < 0.001), UGT2B7*1a carrier status (475 ng/ml increase; 95% confidence interval 138-899 ng/ml, P = 0.004) and CYP2A6*9 and/or *17 carrier status (372 ng/ml increase; 95% confidence interval 74-742 ng/ml, P = 0.013). Overall, CYP2B6 c.516TT genotype, UGT2B7*1a carrier status and CYP2A6*9 or *17 carrier status accounted for 45.2, 10.1 and 8.6% of the total variance, respectively. CONCLUSION: Our findings demonstrate independent effects of CYP2A6 and UGT2B7 genetic variation on efavirenz disposition beyond that of the CYP2B6 polymorphisms. The development and testing of a pharmacogenetic algorithm for estimating the appropriate dose of efavirenz should incorporate genotypic data from both the oxidative and glucuronidation pathways.