HIV symptom severity and associated factors among young people with HIV in Ghana.

ABSTRACTAdolescents and young adults (young people) with HIV (YPWH) often struggle with treatment self-management. Many have symptoms due to HIV disease, medication side-effects, or comorbid conditions. Our study investigated the severity of HIV-related symptoms among YPWH aged 18-24 with detectable viral loads from an HIV clinic in Ghana (N = 60) and potential correlates of severity across a range of factors. Results indicated that YPWH currently experienced, on average, 13 symptoms (SD = 12.33). Six of the 10 most common symptoms were from two domains: fatigue and psychological. The most common symptoms were headaches (62%), weakness (53%), and fear/worries (52%). No differences were observed in number or severity of symptoms between youth based on HIV transmission status. Bivariate correlates of symptom severity were found with six that remained significant or approached significance in a multivariate model predicting severity: living with a parent/guardian, higher perceived access to HIV care, and higher treatment readiness were associated with lower severity while greater travel time to the HIV clinic, psychological distress, and more missed clinic appointments were associated with higher severity. Our findings suggest that interventions to address symptoms among YPWH should be multilevel and include strategies (e.g., telehealth, home care) to increase access to care.

Factors associated with viral suppression and rebound among adult HIV patients on treatment: a retrospective study in Ghana.

BACKGROUND: Viral suppression remains the most desired outcome in the management of patients with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) and this can be achieved by an effective Antiretroviral Therapy (ART). However, some patients who achieve viral suppression may experience viral rebound with dire consequence. We evaluated viral suppression and rebound and their associated factors among adult patients on ART in Kumasi, Ghana. METHODS: This hospital-based retrospective study was conducted at the Komfo Anokye Teaching Hospital in Ghana. We reviewed the medical records of 720 HIV patients on ART. Statistical analyses were performed using SPSS Version 26.0 and GraphPad prism version 8.0. p < 0.05 was considered statistically significant. RESULTS: Proportions of patients with viral suppression and viral rebound were 76.1% and 21.0% respectively. Being diagnosed at WHO stage I [aOR = 11.40, 95% CI (3.54-36.74), p < 0.0001], having good adherence to ART [aOR = 5.09, 95% CI (2.67-9.73), p < 0.0001], taking Nevirapine-based regimen [aOR = 4.66, 95% CI (1.20-18.04), p = 0.0260] and increasing duration of treatment (p < 0.0001) were independently associated with higher odds of viral suppression. However, being diagnosed at WHO stage II (aOR = 7.39, 95% CI 2.67-20.51; p < 0.0001) and stage III (aOR = 8.62, 95% CI 3.16-23.50; p < 0.0001), having poor adherence (aOR = 175.48, 95% CI 44.30-695.07; p < 0.0001), recording baseline suppression value of 20-49 copies/mL (aOR = 6.43, 95% CI 2.72-15.17; p < 0.0001) and being treated with Zidovudine/Lamivudine/Efavirenz (aOR = 6.49, 95% CI 1.85-22.79; p = 0.004) and Zidovudine/Lamivudine/Nevirapine (aOR = 18.68, 95% CI 1.58-220.90; p = 0.02) were independently associated with higher odds of viral rebound. CONCLUSION: Approximately 76% viral suppression rate among HIV patients on ART in Kumasi falls below the WHO 95% target by the year 2030. Choice of ART combination, drug adherence, WHO clinical staging and baseline viral load are factors associated with suppression or rebound. These clinical characteristics of HIV patients must be monitored concurrently with the viral load.

Determinants of post-disclosure violence among women living with HIV in sero-discordant unions in Kumasi, Ghana: a cross-sectional study.

Violence against women is a global challenge with negative health outcomes. Women living with HIV (WLHIV) in sero-discordant unions are at risk of violence after disclosure of their status. This study assesses the risk factors for post-disclosure violence (PDV) against WLHIV in discordant unions in Kumasi, Ghana. A cross-sectional study was conducted among 129 consented WLHIV in discordant relationships in a tertiary facility from May to October 2017. Questionnaire data on socio-demographics and experience of PDV from partners were confidentially obtained. Logistic regression analysis was conducted to assess the independent associations of variables with PDV. PDV was experienced by 19.4% (n = 25) respondents; psychological violence was commonest (80%, n = 20). Women who experienced PDV were more likely to have had a forced first sexual intercourse (43.8% vs 15.9%; aOR 4.1, 95%CI: 1.4-12.4, p = 0.013), be financially independent of their spouses (42.9% vs 12.9%; aOR 0.2, 95%CI: 0.08-0.51, p = 0.001), had partners who interfered with their intake of antiretroviral therapy (50.0% vs 16.5%; aOR 5.1, 95%CI: 1.16-21.99, p = 0.031) or were in a polygamous relationship (63.0% vs 11.8%; aOR 12.8, 95%CI: 4.27-38.32, p < 0.001). The findings from this study indicate an urgent need for the integration of screening for partner violence (especially among WLHIV in discordant unions) and provision of the needed support into national HIV guidelines in Ghana.

Timing of initiation of breastfeeding and its determinants at a tertiary hospital in Ghana: a cross-sectional study.

BACKGROUND: Early initiation of breastfeeding (EIBF), breastfeeding within first hour after birth, is known to have major benefits for both the mother and newborn. EIBF rates, however, tends to vary between and within countries. This study set out to determine the prevalence of EIBF at the Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana, and to evaluate the determinants of EIBF and time to initiation of breastfeeding. METHODS: A cross-sectional study was conducted at the KATH postnatal wards between August and October 2014. Three hundred and eighty-two mothers delivering at KATH were recruited and data on time to initiation of breastfeeding, antenatal, delivery and immediate postnatal periods were collected. Data analyses using both binary and ordinal logistic regressions with stepwise elimination were used to determine the relationship between EIBF and time to initiation of breastfeeding on one side, and the maternal, pregnancy, delivery and neonatal associated factors. RESULTS: EIBF was done in 39.4% (95%CI: 34.3-44.5) of the newborns with breastfeeding initiated between 1 to 6 h for 19.7%, 6 to 11 h in 4.8%, 11 to 16 h in 4.8% and after 16 h in 28.5% of the deliveries. A higher number of antenatal care visits (AOR = 1.14, 95%CI: 1.04-1.25, p = 0.006), delivery by caesarean section (AOR = 0.07, 95%CI: 0.01-0.79, p = 0.031) and infant rooming-in with mother (AOR: 31.67, 95%CI: 5.59-179.43, p <  0.001) were significantly and independently associated with EIBF. Factors independently associated with longer time to initiation of breastfeeding were older maternal age (AOR = 1.04, 95%CI: 1.00-1.09, p = 0.039), Akan ethnicity (AOR = 1.92, 95%CI: 1.14-3.22, p = 0.014), first-born child (AOR = 2.06, 95%CI: 1.18-3.58, p = 0.011), mother rooming-in with newborn (AOR = 0.01. 95%CI: 0.00-0.02, p <  0.001), increasing fifth minute APGAR score (AOR = 0.73, 95%CI: 0.58-0.93, p = 0.010) and using prelacteals (AOR = 2.42, 95%CI: 1.34-4.40, p = 0.004). CONCLUSIONS: The low EIBF rate and prolonged time to initiation of breastfeeding at a major tertiary health facility is a major concern. Key interventions will need to be implemented at KATH and possibly other tertiary healthcare facilities in Ghana and beyond to improve EIBF rate and time to breastfeeding.

Effect of Rifampin-Isoniazid-Containing Antituberculosis Therapy on Efavirenz Pharmacokinetics in HIV-Infected Children 3 to 14 Years Old.

We compared efavirenz pharmacokinetic (PK) parameters in children with tuberculosis (TB)/human immunodeficiency virus (HIV) coinfection on and off first-line antituberculosis therapy to that in HIV-infected children. Children 3 to 14 years old with HIV infection, with and without TB, were treated with standard efavirenz-based antiretroviral therapy without any efavirenz dose adjustments. The new World Health Organization-recommended antituberculosis drug dosages were used in the coinfected participants. Steady-state efavirenz concentrations after 4 weeks of antiretroviral therapy were measured using validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assays. Pharmacokinetic parameters were calculated using noncompartmental analysis. Between groups, PK parameters were compared by Wilcoxon rank-sum test and within group by signed-rank test. Of the 105 participants, 43 (41.0%) had TB coinfection. Children with TB/HIV coinfection compared to those with HIV infection were younger, had lower median weight-for-age Z score, and received a higher median efavirenz weight-adjusted dose. Geometric mean (GM) efavirenz peak concentration (Cmax), concentration at 12 h (C12h), Cmin, and total area under the curve from time 0 to 24 h (AUC0-24h) values were similar in children with HIV infection and those with TB/HIV coinfection during anti-TB therapy. Geometric mean efavirenz C12h, Cmin, and AUC0-24h values were lower in TB/HIV-coinfected patients off anti-TB therapy than in the children with HIV infection or TB/HIV coinfection on anti-TB therapy. Efavirenz clearance was lower and AUC0-24h was higher on than in patients off anti-TB therapy. Reduced efavirenz clearance by first-line anti-TB therapy at the population level led to similar PK parameters in HIV-infected children with and without TB coinfection. Our findings do not support modification of efavirenz weight-band dosing guidelines based on TB coinfection status in children. (The study was registered with ClinicalTrials.gov under registration number NCT01704144.).

Effect of First-Line Antituberculosis Therapy on Nevirapine Pharmacokinetics in Children Younger than Three Years Old.

Nevirapine-based antiretroviral therapy (ART) is one of the limited options in HIV-infected children younger than 3 years old (young children) with tuberculosis (TB) coinfection. To date, there are insufficient data to recommend nevirapine-based therapy during first-line antituberculosis (anti-TB) therapy in young children. We compared nevirapine pharmacokinetics (PK) in HIV-infected young children with and without TB coinfection. In the coinfected group, nevirapine PK was evaluated while on anti-TB therapy and after completing an anti-TB therapy regimen. Of 53 participants, 23 (43%) had TB-HIV coinfection. While the mean difference in nevirapine PK parameters between the two groups was not significant (P > 0.05), 14/23 (61%) of the children with TB-HIV coinfection and 9/30 (30%) with HIV infection had a nevirapine minimum concentration (Cmin) below the proposed target of 3.0 mg/liter (P = 0.03). In multivariate analysis, anti-TB therapy and the CYP2B6 516G>T genotype were joint predictors of nevirapine PK parameters. Differences in nevirapine PK parameters between the two groups were significant in children with CYP2B6 516GG but not the GT or TT genotype. Among 14 TB-HIV-coinfected participants with paired data, the geometric mean Cmin and area under the drug concentration-time curve from time zero to 12 h (AUC0-12) were about 34% lower when patients were taking anti-TB therapy, while the nevirapine apparent oral clearance (CL/F) was about 45% higher. While the induction effect of anti-TB therapy on nevirapine PK in our study was modest, the CYP2B6 genotype-dependent variability in the TB drug regimen effect would complicate any dose adjustment strategy in young children with TB-HIV coinfection. Alternate ART regimens that are more compatible with TB treatment in this age group are needed. (This study has been registered at ClinicalTrials.gov under identifier NCT01699633.).

Population pharmacokinetics of efavirenz in HIV and TB/HIV coinfected children: the significance of genotype-guided dosing.

OBJECTIVES: The current WHO weight-based dosing recommendations for efavirenz result in a wide variability of drug exposure in children. Our objectives are to characterize the effects of rifampicin- and isoniazid-containing anti-TB therapy and CYP2B6 activity on efavirenz concentrations in children, using non-linear mixed-effects modelling. METHODS: This is a pharmacokinetic (PK) substudy of a prospective study that examined the interactions between anti-TB therapy and efavirenz in HIV-infected children with and without TB. PK samples were obtained 4 weeks after starting efavirenz (PK1) and repeated 4 weeks after completing TB therapy (PK2) in TB/HIV coinfected patients. Drug concentrations were measured using LC-MS/MS. Composite CYP2B6 516/983/15582 genotype was determined. Population PK modelling was performed in Monolix. Simulations were performed to obtain the predicted mid-dose concentrations (C12). RESULTS: One hundred and five HIV-infected Ghanaian children (46 with TB/HIV) were included. The median age and weight were 7 years and 19 kg. The efavirenz concentrations over time were adequately described using a one-compartment model. Weight, composite CYP2B6 genotype and PK visit had a significant influence on the PK parameters, while TB therapy had no significant effect. Simulations showed adequate C12 for intermediate composite CYP2B6 metabolizers only. CONCLUSIONS: Our model showed that rifampicin- and isoniazid-containing anti-TB therapy does not influence efavirenz PK parameters. On the other hand, it describes the effect of efavirenz autoinduction after completing TB treatment. In addition, dosing efavirenz in children based only on weight results in a large variability in drug exposure. We propose dose adjustments for slow and extensive composite CYP2B6 metabolizers.

Evaluating the Contribution of Nocardia spp. and Mycobacterium tuberculosis to Pulmonary Infections among HIV and Non-HIV Patients at the Komfo Anokye Teaching Hospital, Ghana.

Tuberculosis (TB) is a major cause of human mortality particularly in association with the human immunodeficiency virus (HIV). Nocardia spp. has emerged as an opportunistic infection especially in HIV patients. The high prevalence of TB and HIV coupled with the lack of a definitive laboratory diagnosis for Nocardia spp. could lead to misdiagnosed pulmonary TB. This study determined the prevalence of pulmonary infections due to Nocardia spp. and Mycobacterium tuberculosis in sputum of HIV and non-HIV patients with suspected pulmonary tuberculosis at KATH. A total of sixty sputum samples were obtained from HIV and non-HIV patients with suspected pulmonary tuberculosis. Samples were examined by fluorescence based Ziehl-Neelsen staining, culture, and PCR methods. The prevalence of Nocardia spp. and Mycobacterium tuberculosis was 18.3% and 20%, respectively, with the latter having the highest rate among patients aged 21-40 years (P=0.075). The prevalence of Nocardia spp. among HIV patients was 90.9% whilst 16.7% of the patients had HIV/Nocardia spp. coinfection. Detection of Mycobacterium tuberculosis by fluorescence-based Ziehl-Neelsen staining, culture, and PCR yielded 9 (15%), 11 (18.3%), and 12 (20%), respectively. There is a high prevalence of nocardiosis especially in HIV patients. PCR is a better diagnostic method that detects both Nocardia spp. and Mycobacterium tuberculosis and should be incorporated into routine diagnosis for pulmonary infections.

Pharmacokinetics of the First-Line Antituberculosis Drugs in Ghanaian Children with Tuberculosis with or without HIV Coinfection.

Although human immunodeficiency virus (HIV) coinfection is the most important risk factor for a poor antituberculosis (anti-TB) treatment response, its effect on the pharmacokinetics of the first-line drugs in children is understudied. This study examined the pharmacokinetics of the four first-line anti-TB drugs in children with TB with and without HIV coinfection. Ghanaian children with TB on isoniazid, rifampin, pyrazinamide, and ethambutol for at least 4 weeks had blood samples collected predose and at 1, 2, 4, and 8 hours postdose. Drug concentrations were determined by validated liquid chromatography-mass spectrometry methods and pharmacokinetic parameters calculated using noncompartmental analysis. The area under the concentration-time curve from 0 to 8 h (AUC0-8), maximum concentration (Cmax), and apparent oral clearance divided by bioavailability (CL/F) for each drug were compared between children with and without HIV coinfection. Of 113 participants, 59 (52.2%) had HIV coinfection. The baseline characteristics were similar except that the coinfected patients were more likely to have lower weight-for-age and height-for-age Z scores (P < 0.05). Rifampin, pyrazinamide, and ethambutol median body weight-normalized CL/F values were significantly higher, whereas the plasma AUC0-8 values were lower, in the coinfected children than in those with TB alone. In the multivariate analysis, drug dose and HIV coinfection jointly influenced the apparent oral clearance and AUC0-8 for rifampin, pyrazinamide, and ethambutol. Isoniazid pharmacokinetics were not different by HIV coinfection status. HIV coinfection was associated with lower plasma exposure of three of the four first-line anti-TB drugs in children. Whether TB/HIV-coinfected children need higher dosages of rifampin, pyrazinamide, and ethambutol requires further investigation. (This study has been registered at ClinicalTrials.gov under identifier NCT01687504.).

Alternative Quantiferon cytokines for diagnosis of children with active tuberculosis and HIV co-infection in Ghana.

IFN-γ release assays (IGRAs) often present false-negative or indeterminate results in children with tuberculosis. HIV co-infection may contribute to decreased sensitivity of IGRAs by impairing T-cell IFN-γ expression. Measurement of alternative cytokines in QuantiFERON® (QFT) supernatants can circumvent the IFN-γ-dependency and may improve QFT sensitivity. We aimed to identify additional cytokines from QFT supernatants for detection of Mycobacterium tuberculosis infection in children with tuberculosis and HIV co-infection from Ghana. Concentrations of 18 cytokines in QFT supernatants from children (0-16 years) with tuberculosis concomitantly infected with HIV (n = 25) or without HIV (n = 24) from Ghana were measured using cytometric bead array (CBA). 29% of the children showed positive IFN-γ test results, and five cytokines, i.e., IL-6, IL-21, TNF-α, IL-1α and IP-10, detected M. tuberculosis infection with comparable or, for IL-6, with significantly higher sensitivity (59%). Increased age and HIV co-infection were associated with decreased cytokine induction, and especially IL-21 and IP-10 were less prevalent in HIV co-infected children with tuberculosis. Combined cytokine analyses increased proportions of positive tests, and a four-cytokine subset (i.e., IL-6, IL-21, IFN-γ, IL-1α) predicted 78% of the children with tuberculosis correctly. Combined evaluation of IFN-γ and alternative cytokines improved IGRA-sensitivity in children with tuberculosis.

Quality of life among Ghanaian adolescents living with perinatally acquired HIV: a mixed methods study.

In Sub-Saharan Africa, increasing numbers of children with perinatally acquired HIV (PAHIV) are living into adolescence. These adolescents face numerous unique challenges such as parent illness/death and years of medication use. Optimizing care for these youth requires an understanding of the factors that contribute to physical health, psychological well-being, social relationships, and quality of life (QOL). This mixed methods study collected quantitative questionnaire data from 40 Ghanaian adolescents with PAHIV (50% female, 12-19 years old) who received care through an adolescent HIV clinic in Kumasi, Ghana. The study also presents results from qualitative interviews conducted with 20 adolescents. Results from quantitative analyses suggested that a significant number of participants were not virally suppressed (67%) and participants reported barriers to treatment adherence, limited social support, concerns about disclosure and HIV-related stigma, limited resources, and lower than expected QOL. Salient themes from the qualitative analyses included limited understanding of how HIV is transmitted, the interplay between food insecurity and treatment adherence and the need for developing safe relationships through which adolescents can discuss their illness without fear of accidental disclosure of their HIV status.

Otoacoustic emission testing in Ghanaian children with sickle-cell disease.

OBJECTIVE: To evaluate hearing loss in children as a complication of sickle-cell disease. METHODS: In Kumasi, Ghana, 35 children with SCD aged 6 months to 10 years underwent transient-evoked otoacoustic emissions testing (TEOAE) to investigate the function of the inner ear. Healthy Ghanaian children recruited in school and kindergarten served as controls. RESULTS: One of 35 children with SCD and 13 of 115 control children failed the otoacoustic emissions testing. This difference between the control group and the children with SCD was not statistically significant. CONCLUSION: Early hearing impairment does not regularly occur in sickle-cell disease, and in children, it is not a likely cause of delayed or impaired language development.

HIV knowledge, stigma, and illness beliefs among pediatric caregivers in Ghana who have not disclosed their child's HIV status.

The majority of HIV-infected children in sub-Saharan Africa have not been informed of their HIV status. Caregivers are reluctant to disclose HIV status to their children because of concern about the child's ability to understand, parental sense of guilt, and fear of social rejection and isolation. We hypothesized that the low prevalence of pediatric HIV disclosure in Ghana is due to lack of accurate HIV information and high HIV stigma among caregivers. This is a preliminary analysis of baseline data of an HIV pediatric disclosure intervention study in Ghana ("Sankofa"). "Sankofa" - is a two-arm randomized controlled clinical trial comparing disclosure intervention plus usual care (intervention arm) vs usual care (control arm) at Korle-Bu Teaching Hospital (KBTH; control arm) and Komfo-Anokye Teaching Hospital (KATH; intervention arm). We enrolled HIV-infected children, ages 7-18 years who do not know their HIV status, and their caregivers. Baseline data of caregivers included demographic characteristics; Brief HIV Knowledge Questionnaire (HIV-KQ-18); Brief Illness Perception Questionnaire; and HIV Stigma Scale. Simple and multivariable linear regression analyses were used to assess the relationship between caregiver characteristics and HIV knowledge, stigma, and illness perception. Two hundred and ninety-eight caregivers were enrolled between January 2013 and July 2014 at the two study sites; KBTH (n = 167) and KATH (n = 131). The median age of caregivers was 41 years; 80.5% of them were female and about 60% of caregivers were HIV-positive. Seventy-eight percent of caregivers were self-employed with low household income. In both unadjusted and adjusted analyses, HIV negative status and lower level of education were associated with poor scores on HIV-KQ. HIV positive status remained significant for higher level of stigma in the adjusted analyses. None of the caregiver's characteristics predicted caregiver's illness perception. Intensification of HIV education in schools and targeted community campaigns are needed.

Discontinuation of maintenance peritoneal dialysis in children-A 10-year review from a single center in a low resource setting.

INTRODUCTION: In South Africa, only children considered eligible for transplantation are offered dialysis as bridge to kidney transplantation. Maintenance peritoneal dialysis (PD) is preferred and has several advantages over hemodialysis (HD). While awaiting transplantation, PD may be discontinued due to permanent transfer to HD or death while on PD, of which the occurrence and burden is not known in our setting. We investigated the rate of discontinuation of maintenance PD, and associated factors among children awaiting a kidney transplant under challenging socio-economic circumstances in a low resource setting. METHODS: Single center retrospective analysis of children receiving maintenance PD. Outcomes included the proportion of children who discontinued PD before transplantation, associated factors and timing of discontinuation, and the proportion transplanted. Time to discontinuation or transplantation was displayed using a Kaplan-Meier curve. RESULTS: Sixty-seven children who received maintenance automated PD as initial dialysis modality were identified from the kidney transplant waiting list between January 2009 and December 2018. Complete data was available for 52 of the 67 children. Four children had prior failed kidney transplants. The median age was 11 years (interquartile range 6.0, 13.1). Overall, 17/52 (32.7%) children discontinued PD, with 13 (25%) transfers to HD and 4 deaths (7.7%), whereas 29/52 (55.8%) received a kidney transplant. Three of the deaths were PD related. Six children remained on maintenance PD at the end of the study period. Over a half of our patients discontinued PD by 12 months, and 80% by 30 months. Most PD discontinuations were associated with peritonitis. CONCLUSIONS: The proportion discontinuing PD was high, highlighting the need to optimize measures to improve retention rates, especially through prevention of peritonitis.

Aetiological agents of pneumonia among HIV and non-HIV infected children in Ghana: A case-control study.

Pneumonia is the leading cause of death in children, however, the microbial aetiology of pneumonia is not well elucidated in low- and middle-income countries. Our study was aimed at determining the microbial aetiologies of childhood pneumonia and associated risk factors in HIV and non-HIV infected children. We conducted a case-control study that enrolled children with pneumonia as cases and non-pneumonia as controls from July 2017 to May 2020. Induced sputum and blood samples were investigated for microbial organisms using standard microbiological techniques. DNA/RNA was extracted from sputum samples and tested for viral and bacterial agents. Four hundred and four (404) subjects consisting of 231 (57.2%) cases and 173 (42.8%) controls were enrolled. We identified a significant (p = 0.011) proportion of viruses in cases (125; 54.1%, 95%CI: 47.4-60.7) than controls (71; 33.6%, 95%CI: 33.6-48.8) and these were mostly contributed to by Respiratory Syncytial Virus. Staphylococcus aureus (16; 4.0%), Klebsiella spp. (15, 3.7%) and Streptococcus pneumoniae (8, 2.0%) were the main bacterial agents identified in sputum or induced sputum samples. HIV infected children with viral-bacterial co-detection were found to have very severe pneumonia compared to those with only viral or bacterial infection. Indoor cooking (OR = 2.36; 95%CI:1.41-3.96) was found to be associated with pneumonia risk in patients. This study demonstrates the importance of various microbial pathogens, particularly RSV, in contributing to pneumonia in HIV and non-HIV paediatric populations. There is a need to accelerate clinical trials of RSV vaccines in African populations to support improvement of patient care.

Pharmacokinetics and pharmacodynamics of adult dolutegravir tablets in treatment-experienced children with HIV weighing at least 20 kg.

OBJECTIVE: Limited pharmacokinetic/pharmacodynamic data are a barrier to the scale-up of dolutegravir-based antiretroviral therapy (ART) in children. We examined the pharmacokinetics/pharmacodynamics of the adult film-coated dolutegravir 50 mg tablets in children with HIV infection weighing at least 20 kg. DESIGN: A prospective, observational, pharmacokinetic, and safety study. METHODS: Treatment-experienced children with HIV weighing at least 20 kg and evidence of viral load suppression on ART were enrolled and switched to dolutegravir-based therapy. After at least 4 weeks and 7 months on dolutegravir-based therapy, blood samples were collected at 0, 1, 4, 8, 12, and 24-h postdose. Dolutegravir concentrations were measured using validated LCMS/MS and pharmacokinetic parameters calculated by noncompartmental analysis. Descriptive statistics were used to summarize pharmacokinetic parameters and comparisons with published reference values. RESULTS: Of 25 participants, 92% were on efavirenz-based ART and 60.0% were men. Dolutegravir mean exposure, peak and trough concentrations at both pharmacokinetic visits were higher than the mean reference values in adults and children weighing 20 kg to less than 40 kg treated with 50 mg once daily, but were closer to the mean values in adults given 50 mg twice a day. Children weighing 20 kg to less than 40 kg had even higher dolutegravir exposures. The regimens were well tolerated with good virologic efficacy through week 48. CONCLUSION: The higher dolutegravir exposure in our study population suggests that further studies and close monitoring should investigate the adverse effects of dolutegravir in more children and in the long term.

Frailty syndrome and associated factors among patients with hypertension: A cross-sectional study in Kumasi, Ghana.

Background and Aim: Frailty is a condition marked by accumulation of biological deficits and dysfunctions that come with aging and it is correlated with high morbidity and mortality in patients with cardiovascular diseases, particularly hypertension. Hypertension continues to be a leading cause of cardiovascular diseases and premature death globally. However, there is dearth of literature in sub-Saharan Africa on frailty syndrome among hypertensives on medication. This study evaluated frailty syndrome and its associated factors among Ghanaian hypertensives. Methods: This cross-sectional study recruited 303 patients with hypertension from the University Hospital, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana. Data on sociodemographic, lifestyle and clinical factors were collected using a well-structured questionnaire. Medication adherence was measured using Adherence in Chronic Disease Scale, and frailty was assessed by Tilburg Frailty Indicator. Statistical analyses were performed using SPSS Version 26.0 and GraphPad prism 8.0. p-value of < 0.05 and 95% confidence interval (CI) were considered statistically significant. Results: The prevalence of frailty was 59.7%. The proportion of high, medium and low medication adherence was 23.4%, 64.4% and 12.2%, respectively. Being ≥ 70years (adjusted odds ratio [aOR]: 8.33, 95% CI [3.72-18.67], p < 0.0001), unmarried (aOR: 2.59, 95% CI [1.37-4.89], p = 0.0030), having confirmed hypertension complications (aOR: 3.21, 95% CI [1.36-7.53], p = 0.0080), medium (aOR: 1.99, 95% CI [1.05-3.82], p = 0.0360) and low antihypertensive drug adherence (aOR: 27.69, 95% CI [7.05-108.69], p < 0.0001) were independent predictors of increased odds of developing frailty syndrome. Conclusion: Approximately 6 out of 10 Ghanaian adult patients with hypertension experience frailty syndrome. Hypertension complications, older age, being unmarried, and low antihypertensive drug adherence increased the chances of developing frailty syndrome. These should be considered in intervention programmes to prevent frailty among patients with hypertension.

Xpert MTB/RIF Ultra and mycobacterial culture in routine clinical care at a paediatric hospital.

Background: Microbiological confirmation of pulmonary tuberculosis (PTB) in children is a well-documented challenge. This study evaluated Xpert Mycobacterium Tuberculosis (MTB)/Rifampicin (RIF) Ultra (Ultra) and mycobacterial cultures in routine clinical care at a tertiary paediatric hospital. Methods: Children treated for PTB and who had at least one respiratory specimen investigated by Ultra and mycobacterial culture before tuberculosis (TB) treatment was commenced were included. The findings of this retrospective study were summarised using descriptive and inferential statistics. Results: A total of 174 children were included. The median age was 2.5 years. Microcytic anaemia, airway compression, cavitary disease and miliary TB were significantly observed in children with microbiologically confirmed TB (cTB). Tuberculosis was microbiologically confirmed in 93 (53.4%) children. The positive yield from testing the first respiratory specimens was 68/174 (39.1%) on Ultra and 82/174 (47.1%) on combined Ultra and mycobacterial culture. In the subset of children (n = 70) tested with Ultra on two sequential respiratory specimens, the incremental yield from the second specimen was 30.3%. In the subset of children (n = 16) tested with Ultra on three sequential respiratory specimens, the incremental yield from the second and third specimens was 16.7% and 0.0%, respectively. When Ultra and mycobacterial culture results were combined, the incremental yield in children who had two sequential respiratory specimens tested was 24.4% and 3.1% on Ultra and mycobacterial culture, respectively. Conclusion: Ultra and mycobacterial culture on a single respiratory specimen resulted in a high microbiological yield. Ultra-testing on a second respiratory specimen increased the yield of microbiologically cTB. Additional diagnostic testing may require further study.

The Impact of Different Parental Figures of Adolescents Living With HIV: An Evaluation of Family Structures, Perceived HIV Related Stigma, and Opportunities for Social Support.

Although antiretroviral therapy (ART) has changed the expected health outcomes for HIV, there are still issues related to stigma, how people living with HIV are perceived, and the availability of social support. The purpose of this study was to explore the associations between family structure and psychosocial wellbeing reflected by perceived HIV stigma and social support among adolescents living with HIV in Kumasi, Ghana. This article used baseline data from two mixed methods studies that evaluated the safety and preliminary efficacy of group-based support programs for ART adherence improvement among adolescents living in Kumasi, Ghana (N = 70, aged 12-18 years). A multivariate linear regression analysis was employed to examine the associations between family structure and the outcomes of stigma and social support. The main variables for family structure were single mothers and female caregivers. We found that single motherhood was a significant determinant of stigma. When compared to other categories of caregiver types, adolescents being raised by their single mothers was associated with a 0.259 decrease in the mean internal HIV stigma score (p = 0.029). Also, for female adolescents, being raised by a female guardian (e.g., mother, aunt, grandmother, and sister) was associated with a 20.92 point increase in the overall support index (p = 0.005). This study shows that the type of parent or guardian, and their gender, influences the perceived stigma and available social support among adolescents living with HIV in Ghana. Vulnerable subgroups of adolescents living with HIV, particularly those raised up by male caregivers, should be provided with additional support.

Pattern of Antimicrobial Susceptibility and Antimicrobial Treatment of Neonates Admitted with Suspected Sepsis in a Teaching Hospital in Ghana, 2021.

Neonatal sepsis is a life-threatening emergency, and empirical antimicrobial prescription is common. In this cross-sectional study of neonates admitted with suspected sepsis in a teaching hospital in Ghana from January-December 2021, we described antimicrobial prescription patterns, compliance with national standard treatment guidelines (STG), blood culture testing, antimicrobial resistance patterns and treatment outcomes. Of the 549 neonates admitted with suspected sepsis, 283 (52%) were males. Overall, 529 (96%) received empirical antimicrobials. Most neonates (n = 407, 76.9%) were treated empirically with cefuroxime + gentamicin, while cefotaxime was started as a modified treatment in the majority of neonates (46/68, 67.6%). Only one prescription complied with national STGs. Samples of 257 (47%) neonates underwent blood culture testing, of which 70 (27%) were positive. Isolates were predominantly Gram-positive bacteria, with coagulase-negative Staphylococcus and Staphylococcus aureus accounting for 79% of the isolates. Isolates showed high resistance to most penicillins, while resistance to aminoglycosides and quinolones was relatively low. The majority of neonates (n = 497, 90.5%) were discharged after successfully completing treatment, while 50 (9%) neonates died during treatment. Strengthening of antimicrobial stewardship programmes, periodic review of STGs and increased uptake of culture and sensitivity testing are needed to improve management of sepsis.