Pharmacogenetic determinants of tenofovir diphosphate and lamivudine triphosphate concentrations in people with HIV/HBV coinfection.

The nucleos(t)ide analogs require phosphorylation to the pharmacologically active anabolites in cells. We investigated the hypothesis that single-nucleotide polymorphisms (SNPs) in genes that encode transporters and phosphodiesterase (PDE) enzymes involved in tenofovir (TFV), disoproxil fumarate (TDF), and lamivudine (3TC) disposition will be associated with concentrations of their phosphate anabolites and virologic response. Individuals with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection receiving TDF/3TC-containing antiretroviral therapy were enrolled. Steady-state TFV diphosphate (TFV-DP) and 3TC triphosphate (3TC-TP) concentrations in peripheral blood mononuclear cells (PBMCs) and dried blood spot samples were quantified. The relationship between genetic variants and TFV-DP and 3TC-TP concentrations as well as with virologic response were examined using multivariable linear regression. Of the 136 participants (median age 43 years; 63% females), 6.6% had HBV non-suppression, and 7.4% had HIV non-suppression. The multidrug resistance protein 2 (encoded by ABCC2 rs2273697) SNP was associated with 3TC-TP concentrations in PBMCs. The human organic anion transporter-1 (encoded by SLC28A2) rs11854484 SNP was associated with HIV non-suppression, and when evaluated together with SNPs with marginal associations (ABCC2 rs717620 and PDE1C rs30561), participants with two or three variants compared to those with none of these variants had an adjusted odds ratio of 48.3 (confidence interval, 4.3-547.8) for HIV non-suppression. None of the SNPs were associated with HBV non-suppression. Our study identified ABCC2 SNP to be associated with 3TC-TP concentrations in PBMCs. Also, a combination of genetic variants of drug transporters and PDE was associated with HIV non-suppression.

Hypertension Among Cohort of Persons With Human Immunodeficiency Virus Initiated on a Dolutegravir-Based Antiretroviral Regimen in Ghana.

Background: Dolutegravir (DTG), a new antiretroviral drug, is being integrated into antiretroviral regimens for people with human immunodeficiency virus (PWH) in Ghana. There is little evidence of the effect of DTG on blood pressure (BP) levels in sub-Saharan Africa, especially West Africa. Our aim was to assess the incidence and predictors of hypertension (HTN) among PWH initiated on a DTG-based antiretroviral regimen in Ghana. Methods: An observational multicenter longitudinal study was conducted among PWH in Ghana from 2020 to 2022. BPs of nonhypertensive patients with BP ≤120/80 mm Hg at baseline were measured at 3, 6, 12, and 18 months post-DTG initiation. The primary outcome of the study was incidence of HTN, defined as BP ≥140/90 mm Hg. Kaplan-Meier estimator was used to estimate risk of developing HTN. Cox proportional hazards model with robust standard errors was used to estimate hazard ratios (HRs). Results: HTN prevalence among PWH screened was 37.3% (1366/3664). The incidence of de novo HTN among nonhypertensive PWH at 72 weeks was 598.4 per 1000 person-years (PY) (95% confidence interval [CI], 559.2-640.3) with incidence proportion of 59.90 (95% CI, 57.30-62.44). A quarter of those with de novo HTN developed it by month 6. Obesity (adjusted HR [aHR], 1.27 [95% CI, 1.05-1.54]), abnormal serum urea (aHR, 1.53 [95% CI, 1.27-1.85]), and low high-density lipoprotein (aHR, 1.45 [95% CI, 1.22-1.72]) were risk factors for HTN. Conclusions: Incidence of HTN was high among PWH on DTG. There is a need to monitor BP for HTN in adult PWH as well as traditional risk factors to reduce the burden of HTN and its complications.

Over forty percent of women living with HIV report interruption in antiretroviral therapy during intrapartum and early postpartum inpatient stay: findings from five hospitals in Ghana.

Antiretroviral therapy (ART) adherence during and after pregnancy is essential to reduce perinatal transmission of HIV. However, little is known about adherence during the intrapartum and early postpartum inpatient hospital stay. Using secondary data from a hospital-based cohort study focused on the relationship between birthweight and engagement in HIV care, we examined the magnitude of, reasons for, and factors associated with incomplete intrapartum and early postpartum ART adherence among adult women (18 years or older) living with HIV who delivered within the previous two weeks at one of five hospitals in Accra, Ghana. Of the 142 enrolled participants who had complete adherence data and reported being on ART at the time of hospital admission, 43% (61/142) reported missing at least one ART dose during labor, delivery, and postpartum, including almost 20% (28/142) missing 2 or more consecutive doses. Women who reported frequently missing ART doses during pregnancy had higher odds of reporting missed doses during their intrapartum and postpartum hospital stays. Among those with inpatient ART interruption, the most frequently cited reasons were: forgetting medication at home (42%) and challenges of being in or recovering from labor (29%). Maternal perception of infant health at birth, hospital level of care, and frequency of missing HIV medications during pregnancy were associated with incomplete ART adherence during the intrapartum and early postpartum inpatient stay. An enabling clinical environment to facilitate access to ART during inpatient stays may have positive implications for ART adherence.

Association of tenofovir diphosphate and lamivudine triphosphate concentrations with HIV and hepatitis B virus viral suppression.

OBJECTIVE: Concentrations of tenofovir diphosphate (TFV-DP) and lamivudine triphosphate (3TC-TP) in cells are correlates of medication adherence and antiviral activity. However, studies have yet to characterize the simultaneous relationship between TFV-DP and 3TC-TP concentrations with HIV and hepatitis B virus (HBV) suppression. METHODS: Individuals with HIV/HBV coinfection on tenofovir disoproxil fumarate (TDF)-containing antiretroviral therapy (ART) were enrolled. Peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS) samples were collected and steady-state TFV-DP and 3TC-TP concentrations quantified using validated methods. The relationship between patient factors, TFV-DP, and 3TC-TP concentrations in PBMCs and DBS with HBV and HIV viral suppression were examined. RESULTS: Of 138 participants on TDF-containing ART for a median duration (range) of 6 (0.75-15) years, the median age was 43 years and 64% were women. Overall, 128 (92.8%) and 129 (93.5%) had suppressed HIV and HBV viral loads, respectively. Of the 128 participants with suppressed HIV, 122 (95.3%) had suppressed HBV. Self-reported ART adherence, recent change to dolutegravir-based ART, TFV-DP, and 3TC-TP concentrations in PBMCs and DBS were associated with HIV RNA suppression, while HBe antigen positivity, HIV suppression, and TFV-DP concentrations in DBS were associated with HBV DNA suppression (including six persons with HBV nonsuppression and HIV suppression). CONCLUSION: Long-term TDF/3TC-conatining ART was highly efficacious in individuals with HIV/HBV coinfection. Higher TFV-DP concentrations were predictive of suppression for both viruses. Persistent HBV viremia on TDF/3TC-containg ART requires additional research, but may represent poor adherence and the need for adherence interventions or novel antivirals.

Pediatric HIV Disclosure Intervention Improves Immunologic Outcome at 48 Weeks: The Sankofa Trial Experience.

BACKGROUND: The World Health Organization recommends disclosure of HIV status to children and adolescents living with HIV (CALWH). HIV disclosure improves adherence to antiretroviral therapy and immunologic and virologic outcomes. However, the prevalence of HIV disclosure is low in sub-Saharan Africa. We assessed the longitudinal effect of the Sankofa Pediatric HIV disclosure intervention on immunologic and virologic outcomes among CALWH in Ghana. METHODS: We conducted a secondary analysis of a two-arm site-randomized clinical trial among CALWH aged 7-18 years. Data were collected at baseline, 24, and 48 weeks. Generalized linear mixed models were used to compare immunologic (CD4) and virologic (viral load) outcomes as both continuous and categorical variables by disclosure status and by intervention group. RESULTS: Among participants who had their HIV status disclosed during this study, the proportion with CD4 percent >25% increased from 56.5% at baseline to 75.4% at week 48 ( P = 0.03), with a slight increase in the undisclosed group (69.5% vs. 74.3%, P = 0.56). In the intervention arm, there was a steady increase in proportion with CD4 percent >25% from 47.1% at baseline to 67.8% at week 48 ( P = 0.01) while it remained unchanged in the control arm (80.5% vs. 81.3% [ P = 0.89]). Concurrently, declines in detectable viral load were observed in both disclosed (63.3% vs. 51.5%, P = 0.16) and undisclosed (69.9% vs. 62.0%, P = 0.17) groups while the intervention group experienced a meaningful drop from 72.9% to 57.6% at 24 weeks ( P = 0.04), which was maintained at 48 weeks. CONCLUSIONS: A structured, culturally relevant disclosure intervention can improve clinical outcomes.

Risk factors for COVID-19 infections among health care workers in Ghana.

INTRODUCTION: Health care workers (HCWs) are crucial to the fight against COVID-19 and are at risk of being infected. We sought to determine the risk factors and associations of COVID-19 among HCWs in Ghana during the period of the pandemic. MATERIALS AND METHODS: A case-control study was conducted using the WHO COVID-19 HCWs exposure risk assessment tool. A HCW was categorized as "high risk" for COVID-19 if s/he did not respond "always, as recommended" to adherence to Infection Prevention and Control (IPC) measures during a healthcare interaction. A HCW was categorized as "low risk" if s/he responded "always, as recommended" to adherence to IPC measures. We used univariate and multiple logistic regression models to determine associated risk factors. Statistical significance was set at 5%. RESULTS: A total of 2402 HCWs were recruited and the mean age was 33.2±7.1 years. Almost 87% (1525/1745) of HCWs had high risk for COVID-19 infection. Risk factors identified were profession (doctor- aOR: 2.13, 95%CI: 1.54-2.94; radiographer-aOR: 1.16, 95% CI: 0.44-3.09)), presence of comorbidity (aOR: 1.89, 95%CI: 1.29-2.78), community exposure to virus (aOR: 1.26, 95% CI: 1.03-1.55), not performing hand hygiene before and after aseptic procedures performed (aOR: 1.6, 95% CI: 1.05-2.45); not frequently decontaminating high-touch surfaces always as recommended (aOR: 2.31, 95%CI: 1.65-3.22; p = 0.001) and contact with a confirmed COVID-19 patient (aOR: 1.39, 95% CI: 1.15-1.67). Among those who came into any form of contact with confirmed COVID-19 patient, providing direct care (aOR: 2.0, 95%CI: 1.36-2.94), face-to-face contact (aOR: 2.23, 95%CI: 1.41-3.51), contact with environment/materials used by COVID-19 patient (aOR: 2.25, 95%CI: 1.45-3.49) and presence during conduct of aerosol generating procedures (aOR: 2.73, 95%CI: 1.74-4.28) were associated with COVID-19 infection. CONCLUSION: Non-adherence to IPC guidelines puts HCWs at increased risk of COVID-19 infection thus ensuring IPC adherence is key to reducing this risk.

Point-of-Care Urine Lipoarabinomannan Testing to Guide Tuberculosis Treatment Among Severely Ill Inpatients With Human Immunodeficiency Virus in Real-World Practice: A Multicenter Stepped Wedge Cluster-Randomized Trial From Ghana.

BACKGROUND: The lateral flow urine lipoarabinomannan assay, Determine TB LAM (Determine LAM), offers the potential for timely tuberculosis (TB) treatment among people with human immunodeficiency virus (PWH). METHODS: In this cluster-randomized trial, Determine LAM was made available with staff training with performance feedback at 3 hospitals in Ghana. Newly admitted PWH with a positive World Health Organization four-symptom screening for TB, severe illness, or advanced HIV were enrolled. The primary outcome was days from enrollment to TB treatment initiation. We also reported the proportion of patients with a TB diagnosis, initiating TB treatment, all-cause mortality, and Determine LAM uptake at 8 weeks. RESULTS: We enrolled 422 patients including 174 (41.2%) in the intervention group. The median CD4 count was 87 (interquartile range [IQR], 25-205) cells/µL, and 32.7% were on antiretroviral therapy. More patients were diagnosed with TB in the intervention compared with the control group: 59 (34.1%) versus 46 (18.7%) (P < .001). Time to TB treatment remained constant, but patients were more likely to initiate TB treatment (adjusted hazard ratio, 2.19 [95% CI, 1.60-3.00]) during the intervention. Of patients with a Determine LAM test available, 41 (25.3%) tested positive. Of those, 19 (46.3%) initiated TB treatment. Overall, 118 patients had died (28.2%) at 8 weeks of follow-up. CONCLUSIONS: The Determine LAM intervention in real-world practice increased TB diagnosis and the probability of TB treatment but did not reduce time to treatment initiation. Despite high uptake, only half of the LAM-positive patients initiated TB treatment.

The in-hospital tuberculosis diagnostic cascade and early clinical outcomes among people living with HIV before and during the COVID-19 pandemic - a prospective multisite cohort study from Ghana.

OBJECTIVES: The COVID-19 pandemic had a disruptive impact on tuberculosis (TB) and HIV services. We assessed the in-hospital TB diagnostic care among people with HIV (PWH) overall and before and during the pandemic. METHODS: In this prospective study, adult PWH admitted at three hospitals in Ghana were recruited if they had a positive World Health Organization four-symptom screen or one or more World Health Organization danger signs or advanced HIV. We collected data on patient characteristics, TB assessment, and clinical outcomes after 8 weeks and used descriptive statistics and survival analysis. RESULTS: We enrolled 248 PWH with a median clusters of differentiation 4 count of 80.5 cells/mm3 (interquartile range 24-193). Of those, 246 (99.2%) patients had a positive World Health Organization four-symptom screen. Overall, 112 (45.2%) patients obtained a sputum Xpert result, 66 (46.5%) in the prepandemic and 46 (43.4%) in the pandemic period; P-value = 0.629. The TB prevalence of 46/246 (18.7%) was similar in the prepandemic 28/140 (20.0%) and pandemic 18/106 (17.0%) population; P-value = 0.548. The 8-week all-cause mortality was 62/246 (25.2%), with no difference in cumulative survival when stratifying for the pandemic period; log-rank P-value = 0.412. CONCLUSION: The study highlighted a large gap in the access to TB investigation and high early mortality among hospitalized PWH, irrespective of the COVID-19 pandemic.

Use of the urine Determine LAM test in the context of tuberculosis diagnosis among inpatients with HIV in Ghana: a mixed methods study.

Background: The urine Determine LAM test has the potential to identify tuberculosis (TB) and reduce early mortality among people living with HIV. However, implementation of the test in practice has been slow. We aimed to understand how a Determine LAM intervention was received and worked in a Ghanaian in-hospital context. Design/Methods: Nested in a Determine LAM intervention study, we conducted a two-phase explanatory sequential mixed methods study at three hospitals in Ghana between January 2021 and January 2022. We performed a quantitative survey with 81 healthcare workers (HCWs), four qualitative focus-group discussions with 18 HCWs, and 15 in-depth HCW interviews. Integration was performed at the methods and analysis level. Descriptive analysis, qualitative directed content analysis, and mixed methods joint display were used. Results: The gap in access to TB testing when relying on sputum GeneXpert MTB/Rif alone was explained by difficulties in obtaining sputum samples and an in-hospital system that relies on relatives. The Determine LAM test procedure was experienced as easy, and most eligible patients received a test. HCWs expressed that immediate access to Determine LAM tests empowered them in rapid diagnosis. The HCW survey confirmed that bedside was the most common place for Determine LAM testing, but qualitative interviews with nurses revealed concerns about patient confidentiality when performing and disclosing the test results at the bedside. Less than half of Determine LAM-positive patients were initiated on TB treatment, and qualitative data identified a weak link in the communication of the Determine LAM results. Moreover, HCWs were reluctant to initiate Determine LAM-positive patients on TB treatment due to test specificity concerns. The Determine LAM intervention did not have an impact on the time to TB treatment as expected, but patients were, in general, initiated on TB treatment rapidly. We further identified a barrier to accessing TB treatment during weekends and that treatment by tradition is administrated early in the morning. Conclusion: The Determine LAM testing was feasible and empowered HCWs in the management of HIV-associated TB. Important gaps in routine care and Determine LAM-enhanced TB care were often explained by the context. These findings may inform in-hospital quality improvement work and scale-up of Determine LAM in similar settings.

Diagnostic Accuracy of Urine Lipoarabinomannan Testing in Early Morning Urine versus Spot Urine for Diagnosis of Tuberculosis among People with HIV.

The Fujifilm SILVAMP TB LAM (FujiLAM) assay offers improved sensitivity compared to Determine TB LAM Ag (AlereLAM) for detecting tuberculosis (TB) among people with HIV. Here, we examined the diagnostic value of FujiLAM testing on early morning urine versus spot urine and the added value of a two-sample strategy. We assessed the diagnostic accuracy of FujiLAM on cryopreserved urine samples collected and stored as part of a prospective cohort of adults with HIV presenting for antiretroviral treatment in Ghana. We compared FujiLAM sensitivity and specificity in spontaneously voided urine samples collected at inclusion (spot urine) versus in the first voided early morning urine (morning urine) and for a one (spot urine) versus two samples (spot and morning urine) strategy. Diagnostic accuracy was determined against both microbiological (using sputum culture and Xpert MTB/RIF testing of sputum and urine to confirm TB) and composite reference standards (including microbiologically confirmed and probable TB cases). Paired urine samples of spot and morning urine were available for 389 patients. Patients had a median CD4 cell count of 176 cells/µL (interquartile range [IQR], 52 to 361). Forty-three (11.0%) had confirmed TB, and 19 (4.9%) had probable TB. Overall agreement for spot versus morning urine test results was 94.6% (kappa, 0.81). Compared to a microbiological reference standard, the FujiLAM sensitivity (95% confidence interval [CI]) was 67.4% (51.5 to 80.9) for spot and 69.8% (53.9 to 82.8) for morning urine, an absolute difference (95% CI) of 2.4% (-10.2 to 14.8). Specificity was 90.2% (86.5 to 93.1) versus 89.0% (85.2 to 92.1) for spot and morning urine, respectively, a difference of 1.2% (-3.7 to 1.4). A two-sample strategy increased FujiLAM sensitivity from 67.4% (51.5 to 80.9) to 74.4% (58.8 to 86.5), a difference of 7.0% (-3.0 to 16.9), while specificity decreased from 90.2% (86.5 to 93.1) to 87.3% (83.3 to 90.6), a difference of -2.9% (-4.9 to -0.8). This study indicates that FujiLAM testing performs equivalently on spot and early morning urine samples. Sensitivity could be increased with a two-sample strategy but at the risk of lower specificity. These data can inform future guidelines and clinical practice. IMPORTANCE This study indicates that FujiLAM testing performs equivalently on spot and early morning urine samples for detecting tuberculosis among people with HIV. Sensitivity could be increased with a two-sample strategy but at the risk of lower specificity. These data can inform future guidelines and clinical practice around FujiLAM.

Preferences for a Game-Based SMS Adherence Intervention Among Young People Living with HIV in Ghana: A Qualitative Study.

Young people living with HIV (YPLH) are at risk for poor treatment adherence. Short message service (SMS) interventions can improve adherence, yet few exist for YPLH. Our study investigated preferences for a game-based SMS intervention among YPLH in Ghana. Thirty-two YPLH, ages 18 to 24, were recruited from an HIV clinic to complete in-depth interviews. Content analysis of interview data revealed areas of technology use relevant to intervention implementation, including mobile communication preferences, internet access, and mobile game use. Participants reported high perceived utility towards intervention features: treatment reminders, gamification components, and involvement of supportive individuals (e.g., providers). Issues with privacy, literacy, and cultural/developmental appropriateness were among concerns raised. Suggestions were made for strengthening basic SMS features (e.g., using code words to protect privacy) and incorporating advanced features (e.g., simplifying game interactions). This novel approach may help engage YPLH in HIV care if carefully developed with attention towards its mechanisms and user preferences.

Antiretroviral therapy adherence and viral suppression among HIV-infected adolescents and young adults at a tertiary hospital in Ghana.

With the introduction of antiretroviral therapy (ART), many HIV-infected children are growing into adolescence and adulthood. A facility-based cross-sectional study was conducted at the Fevers Unit of one of the teaching hospitals in Ghana. The Morisky Medication Adherence Scale (MMAS-8) and pill count were used to assess adherence, while measured viral load levels of participants were used to assess viral suppression. The rate of viral suppression (<400 copies/ml) was 68.2%. Participants with high MMAS-8 scores were 8.4 times more likely to be virally suppressed compared to those with low MMAS-8 scores (OR = 8.4, p = 0.003, 95% CI: 2.11-33.48). The commonest reason for missing doses of their antiretroviral drugs (ARVs) was forgetfulness. Efforts must be made by all stakeholders involved in HIV care to engage adolescents and young adults living with HIV (AYALHIV) on personal and/or group levels to help identify and improve particular ART adherence issues so as to increase viral suppression rates.

Prevalence of pneumonia by chest x-ray, associated demographic characteristics and health risk factors among COVID-19 patients in Ghana.

OBJECTIVE: The study was conducted to determine the prevalence of radiologically diagnosed pneumonia among COVID-19 patients and associated factors. DESIGN SETTING AND PARTICIPANTS: A retrospective manual data extraction of 275 medical records of COVID-19 patients was conducted at two COVID-19 national treatment centres in Accra from March to May 2020. All patients had a chest x-ray done. MAIN OUTCOME AND ANALYSIS: The main outcome was the presence of pneumonia. Descriptive statistics and Chi-square test of independence were employed to determine the associations between independent variables and the presence of pneumonia. All analysis was performed using Stata 16, and a p-value ≤ 0.05 was deemed significant. RESULTS: The prevalence of pneumonia was 44%(95%CI) =38.2-50.0). Chi-square independent test indicated that pneumonia in the COVID-19 patients was associated with educational level, history of domestic and international travel, mass gathering in the past 14 days before diagnosis, and discharge plan (p-value< 0.05). Patients classified as secondary cases (61.5%) and those discharged as fully recovered from the health facility (61.2%) had a higher prevalence of pneumonia. In addition, COVID-19 patients with hypertension (32.1%) and asthma (5.2%) had a significantly higher prevalence of pneumonia. CONCLUSION: Overall, the prevalence of pneumonia was 44% and was associated with the demographic and personal characteristics of the patients. Early detection through contact tracing and community surveillance should be intensified to pick up more asymptomatic cases. The role of the chest x-ray for triaging patients and for clinical management of symptomatic patients remains key. FUNDING: None declared.

Stigma toward small babies and their mothers in Ghana: A study of the experiences of postpartum women living with HIV.

Infants born to HIV-infected mothers are more likely to be low birthweight (LBW) than other infants, a condition that is stigmatized in many settings worldwide, including sub-Saharan Africa. Few studies have characterized the social-cultural context and response to LBW stigma among mothers in sub-Saharan Africa or explored the views of women living with HIV (WLHIV) on the causes of LBW. We purposively sampled thirty postpartum WLHIV, who had given birth to either LBW or normal birthweight infants, from two tertiary hospitals in Accra, Ghana. Using semi-structured interviews, we explored women's understanding of the etiology of LBW, and their experiences of caring for a LBW infant. Interviews were analyzed using interpretive phenomenology. Mothers assessed their babies' smallness based on the baby's size, not hospital-recorded birthweight. Several participants explained that severe depression and a loss of appetite, linked to stigma following an HIV diagnosis during pregnancy, contributed to infants being born LBW. Women with small babies also experienced stigma due to the newborns' "undesirable" physical features and other people's unfamiliarity with their size. Consequently, mothers experienced blame, reluctance showing the baby to others, and social gossip. As a result of this stigma, women reported self-isolation and depressive symptoms. These experiences were layered on the burden of healthcare and infant feeding costs for LBW infants. LBW stigma appeared to attenuate with increased infant weight gain. A few of the women also did not breastfeed because they thought their baby's small size indicated pediatric HIV infection. Among WLHIV in urban areas in Ghana, mother and LBW infants may experience LBW-related stigma. A multi-component intervention that includes reducing LBW incidence, treating antenatal depression, providing psychosocial support after a LBW birth, and increasing LBW infants' weight gain are critically needed.

Pharmacokinetics of Efavirenz 600 mg Once Daily During Pregnancy and Post Partum in Ghanaian Women Living With HIV.

PURPOSE: The updated World Health Organization guidelines recommend efavirenz (EFV) 400 mg as the preferred alternate first-line antiretroviral therapy to dolutegravir, with EFV 600 mg recommended only in special situations. We examined the pharmacokinetic (PK) properties of EFV 600 mg/d during pregnancy and post partum to inform EFV dosing decisions in pregnant women. METHODS: Ghanaian pregnant women with HIV infection initiating tenofovir disoproxil fumarate 300 mg/lamivudine 300 mg/EFV 600 mg fixed-dose combination tablet once daily were enrolled. Efavirenz concentrations were measured at 4 weeks of antiretroviral therapy initiation during pregnancy and 6 weeks post partum using validated LC-MS/MS assays. Efavirenz PK parameters were calculated using noncompartmental analysis, and within-group parameters between the 2 periods were compared. FINDINGS: Of 25 enrolled women, 19 completed PK sampling during pregnancy and post partum. The Cmax, Cmin, AUC0-24h, and CL/F for EFV during pregnancy were similar to values at 6 weeks post partum. The pregnancy/postpartum geometric mean ratios for EFV Cmax, Cmin, AUC0-24, and CL/F were 1.10 (95% CI, 0.93-1.31), 0.88 (95% CI, 0.67-1.17), 0.84 (95% CI, 0.71-0.98), and 1.20 (95% CI, 1.02-1.40), respectively. Viral load suppression (HIV RNA <200 copies/mL) was achieved in 16 of 17 participants (94%) by the time of delivery. There was 1 maternal-to-child transmission. IMPLICATIONS: We found that the PK parameters of EFV 600 mg once daily during pregnancy were similar to those in the postpartum period. Our findings suggest that EFV dose adjustment during pregnancy is not necessary in our study population.

Barriers to maternal retention in HIV care in Ghana: key differences during pregnancy and the postpartum period.

BACKGROUND: Maternal retention in HIV care is lower for women in the postpartum period than during pregnancy, but the reasons are poorly understood. We examined key differences in barriers to retention in HIV care during and after pregnancy. METHODS: We conducted semi-structured, in-depth interviews with 30 postpartum women living with HIV. Participants were recruited from two tertiary facilities implementing Option B+ for prevention of mother-to-child HIV transmission in Accra, Ghana. We collected data from mothers who had disengaged from HIV care and those who were still engaged in care. The interviews were analyzed using principles adapted from grounded theory. RESULTS: Participants' experiences and narratives showed that retention in HIV care was more challenging during the postpartum period than during pregnancy. Poor maternal physical health (from birth complications and cesarean section), socio-cultural factors (norms about newborn health and pregnancy), and economic difficulties linked to childbirth (such as unemployment, under-employment, and debt) made the costs of retention in HIV care more economically and socially expensive in the postpartum period than during pregnancy. Some participants also shared that transportation costs and resulting dependence on a partner to pay increased during the postpartum period because of a strong shift in maternal preference for private modes of transportation due to HIV stigma and the desire to protect the newborn. These factors played a larger role in the postpartum period than during pregnancy and created a significant barrier to retention. A conceptual model of how these factors interrelate, the synergy between them, and how they affect retention in the postpartum period is presented. CONCLUSIONS: In Ghana, lower retention in HIV care in the postpartum period compared to in pregnancy may be primarily driven by social, economic, and newborn health factors. Multifaceted economic-based and stigma-reduction interventions are needed to increase retention in maternal HIV care after childbirth.

Illness Narratives of Children Living with HIV Who Do Not Know Their HIV Status in Ghana: I'm Sick, But I Don't Know the Sickness-A Qualitative Study.

Despite available guidelines for disclosure of HIV status to children, most children living with HIV are unaware of their diagnosis. We sought to characterize the concepts of illness and treatment among children living with HIV who do not know their status. As part of the Sankofa trial we interviewed 435 children aged 6-18 enrolled in clinical care at pediatric HIV clinics at two teaching hospitals in Ghana. Theoretic thematic analysis generated themes among responses. The children believe they come to the clinic to collect medication, to address specific symptoms, to prevent and treat 'sickness', or as part of their routine. Most children learned of their 'illness' from a family member. A majority (73.5%) of children had never talked about their 'illness' with anyone else; many feared consequences. Children living with HIV who do not know their status exhibit signs of anticipated and internalized stigma regarding their unknown 'illness.' An understanding of the way children conceptualize their illness has implications for health promotion and the provision of appropriate information to children living with HIV.ClinicalTrials.gov Identifier NCT01701635.

RESUMEN: A pesar de las pautas disponibles para la divulgación del estado del VIH a los niños, la mayoría de los niños que viven con el VIH desconocen su diagnóstico. Intentamos describir los conceptos de enfermedad y tratamiento entre los niños que viven con el VIH que no conocen su estado de infeccion. Como parte del ensayo Sankofa, entrevistamos a 435 niños de 6 a 18 años inscritos en atención clínica cuidado en clínicas pediátricas de VIH en dos hospitales docentes en Ghana. El análisis temático teórico generó temas entre las respuestas obtenidas. Los niños creen que vienen a la clínica a recoger medicamentos, a tratar síntomas específicos, a prevenir y tratar "condiciones" o como parte de su cuidado rutinario. A traves de entrevistas, aprendimos que la mayoría de los niños aprendieron de su "enfermedad" de un miembro de la familia. Esta mayoría (73.5%) nunca habían hablado sobre su "enfermedad" con nadie más; debido a muchas consecuencias temidas. Los niños que viven con VIH que no conocen su estado, exhiben signos de estigma anticipado e internalizado con respecto a su "enfermedad" desconocida. El entender la forma en que los niños conceptualizan su enfermedad tiene implicaciones para la promoción de la salud y el suministro de información adecuada a los niños que viven con el VIH.

Resilience and pathways to wellness among HIV-positive patients in Ghana: a qualitative study.

Few African studies have focused on resilience factors related to engagement in HIV-related care among people living with HIV; instead, many studies have identified health risk factors and barriers within this population. Informed by the Disability-Stress-Coping Model of Adjustment, a qualitative study was conducted to develop a better understanding of psychosocial factors that can promote positive behaviours and subjective wellness for people living with HIV in Accra, Ghana. Thirty patients from the two largest HIV clinics in Accra participated in in-depth individual interviews. Using a thematic analysis approach, three individual-level factors related to resilience and subjective wellness were identified: (1) holding positive attitudes towards the pathway from HIV testing and diagnosis to healthy living with HIV; (2) placing appropriate (but not absolute) levels of trust in the clinical care environment; and (3) judicious disclosure of their HIV status to key individuals. Findings support a resilience framework that focuses on individual strengths and positive adaptations to HIV diagnosis in order to enhance understanding and promote the HIV care continuum for people living with HIV in this context. Development of resilience-focused approaches to public health intervention is particularly important in low-resource settings such as Ghana where research tends to focus on deficiencies and healthcare inadequacies for people living with HIV.

Clinic-Based Pediatric Disclosure Intervention Trial Improves Pediatric HIV Status Disclosure in Ghana.

BACKGROUND: Disclosing HIV status to HIV-positive children is a major challenge facing families and health care providers. Despite recommendations for disclosure, rates remain low. We tested whether a pediatric HIV disclosure intervention delivered as an integral component of routine HIV health care in Ghana would improve disclosure to children. METHODS: Dyads of HIV-infected children aged 7-18 years and their caregivers were enrolled from 2 HIV clinics in Accra and Kumasi, Ghana. The sites were randomly assigned to one of the 2 intervention arms to avoid treatment contamination between intervention and control participants. Trained interventionist used theory-guided therapeutic communication and personalized interaction to promote disclosure. Disclosure outcomes were measured at 12-week intervals. All analyses were completed using a modified intention-to-treat approach. RESULTS: We enrolled 446 child-caregiver dyads (N = 240 intervention group; N = 206 control group); 52% of the children were boys, mean age 9.78 (±2.27) years. For disclosure at 1 year, a better overall treatment effect was observed (P < 0.001). Children in the treatment group had greater disclosure at each time point (P < 0.001) and a higher proportion of them had been disclosed to by 1 year (51.4% vs. 16.2%; P < 0.001; un-adjusted hazard ratio = 3.98: 95% confidence interval: 2.63 to 6.03) and 3 years (71.3% vs. 34.0%; unadjusted hazard ratio = 4.21: 95% confidence interval: 3.09 to 5.72). In the multivariate Cox model, factors associated with disclosure were treatment group (P < 0.001), children <11 years of age (P < 0.001), HIV-infected caregivers (P = 0.015), and caregiver's with greater education (P = 0.022). CONCLUSIONS: This practical clinic-based disclosure intervention shows excellent promise as a means of improving HIV pediatric disclosure outcomes.