Validation of a brief mental health screening tool for common mental disorders in primary healthcare

Background. Integrating care for common mental disorders (CMDs) such as depression, anxiety and alcohol abuse into primary healthcare (PHC) should assist in reducing South Africa (SA)’s quadruple burden of disease. CMDs compromise treatment adherence, health behaviour change and self-management of illnesses. Appropriate identification of mental disorders in primary care can be facilitated by brief, easy-to-administer screening that promotes high specificity.Objectives. To establish the criterion-based validity of a seven-item Brief Mental Health (BMH) screening tool for assessing positive symptoms of CMDs in primary care patients.Methods. A total of 1 214 participants were recruited from all patients aged ≥18 years visiting 10 clinics as part of routine care in the Newcastle subdistrict of Amajuba District in KwaZulu-Natal Province, SA, over a period of 2 weeks. Consenting patients provided basic biographical information prior to screening with the BMH tool. PHC nurses remained blind to this assessment. PHC nurse-initiated assessment using the Adult Primary Care (APC) guidelines was the gold standard against which the performance of the BMH tool was compared. A specificity standard of 80% was used to establish cut-points. Specificity was favoured over sensitivity to ensure that those who did not have CMD symptoms were excluded, as well as to reduce over-referrals.Results. Of the participants, 72% were female. The AUD-C (alcohol abuse) performed well (area under the curve (AUC) 0.91 (95% confidence interval (CI) 0.88 - 0.95), cut-point ≥4, Cronbach alpha 0.87); PHQ-2 (depression) performed reasonably well (AUC 0.72 (95% CI 0.65 - 0.78), cut-point ≥3, alpha 0.71); and GAD-2 (anxiety) performance was acceptable (AUC 0.69 (95% CI 0.58 - 0.80), cut-point ≥3, alpha 0.62). Using the higher cut-off scores, patients who truly did not have CMD symptoms had negative predictive values (NPVs) of >90%. Overall, 26% of patients had CMD positive symptoms relative to 8% using the APC guidelines.Conclusions. Using a higher specificity index, the positive predictive value and NPV show that at higher cut-point values the BMH not only helps identify individuals with alcohol misuse, depression and anxiety symptoms but also identifies a majority of those who do not have symptoms (true negatives), thus not overburdening nurses with false positives needing assessment. Research is needed to assess whether use of such a short and valid screening tool is generalisable to other clinic contexts as well as how mental health screening should best be introduced into routine clinic functioning and practice.

Final 192-week efficacy and safety results of the ADVANCE trial, comparing 3 first-line antiretroviral regimens

BACKGROUND: ADVANCE compared 3 World Health Organization-recommended first-line regimens in participants with HIV who were antiretroviral naive. METHODS: This randomized, open-label, noninferiority trial enrolled participants living with HIV with no antiretroviral exposure in the previous 6 months to 1 of the following arms: tenofovir alafenamide (TAF) / emtricitabine (FTC) + dolutegravir (DTG) (2 tablets), tenofovir disoproxil fumarate (TDF) / FTC + DTG (2 tablets), or a fixed-dose combination of TDF / FTC / efavirenz (EFV) (1 tablet). We report the final safety and efficacy data up to 192 weeks. RESULTS: Repeat consent from the original 351 participants randomized to each arm was obtained from 230 participants (66%) in the TAF/FTC + DTG arm, 209 (60%) in the TDF/FTC + DTG arm, and 183 (52%) in the TDF/FTC/EFV arm. At 192 weeks, 213 (61%) of the original 351 participants in the TAF/FTC + DTG arm, 195 (56%) in the TDF/FTC + DTG arm, and 172 (49%) in the TDF/FTC/EFV arm had confirmed RNA <50 copies/mL, with low virologic failure in all groups and no significant integrase inhibitor mutations in any arm. Mean weight gain was 8.9 kg (SD, 7.1) in the TAF/FTC + DTG arm, 5.9 kg (SD, 7.1) in the TDF/FTC + DTG arm, and 3.2 kg (SD, 8.1) in the TDF/FTC/EFV arm at 192 weeks from baseline and was greatest among women, those taking TAF, and those with lower baseline CD4 counts. The weight trajectory slowed after week 96. There were few clinical events and minor laboratory changes and differences among arms after 96 weeks. There were no significant differences in treatment-emergent hypertension or pregnancy outcomes by arm. CONCLUSIONS: High viral suppression was seen across arms, with no resistance to DTG. Weight gain continued but slowed after 96 weeks, with few clinical events or laboratory changes

Validation of a brief mental health screening tool for common mental disorders in primary healthcare

Background. Integrating care for common mental disorders (CMDs) such as depression, anxiety and alcohol abuse into primary healthcare (PHC) should assist in reducing South Africa (SA)’s quadruple burden of disease. CMDs compromise treatment adherence, health behaviour change and self-management of illnesses. Appropriate identification of mental disorders in primary care can be facilitated by brief, easy-to-administer screening that promotes high specificity.Objectives. To establish the criterion-based validity of a seven-item Brief Mental Health (BMH) screening tool for assessing positive symptoms of CMDs in primary care patients.Methods. A total of 1 214 participants were recruited from all patients aged ≥18 years visiting 10 clinics as part of routine care in the Newcastle subdistrict of Amajuba District in KwaZulu-Natal Province, SA, over a period of 2 weeks. Consenting patients provided basic biographical information prior to screening with the BMH tool. PHC nurses remained blind to this assessment. PHC nurse-initiated assessment using the Adult Primary Care (APC) guidelines was the gold standard against which the performance of the BMH tool was compared. A specificity standard of 80% was used to establish cut-points. Specificity was favoured over sensitivity to ensure that those who did not have CMD symptoms were excluded, as well as to reduce over-referrals.Results. Of the participants, 72% were female. The AUD-C (alcohol abuse) performed well (area under the curve (AUC) 0.91 (95% confidence interval (CI) 0.88 - 0.95), cut-point ≥4, Cronbach alpha 0.87); PHQ-2 (depression) performed reasonably well (AUC 0.72 (95% CI 0.65 - 0.78), cut-point ≥3, alpha 0.71); and GAD-2 (anxiety) performance was acceptable (AUC 0.69 (95% CI 0.58 - 0.80), cut-point ≥3, alpha 0.62). Using the higher cut-off scores, patients who truly did not have CMD symptoms had negative predictive values (NPVs) of &gt;90%. Overall, 26% of patients had CMD positive symptoms relative to 8% using the APC guidelines.Conclusions. Using a higher specificity index, the positive predictive value and NPV show that at higher cut-point values the BMH not only helps identify individuals with alcohol misuse, depression and anxiety symptoms but also identifies a majority of those who do not have symptoms (true negatives), thus not overburdening nurses with false positives needing assessment. Research is needed to assess whether use of such a short and valid screening tool is generalisable to other clinic contexts as well as how mental health screening should best be introduced into routine clinic functioning and practice.Â

Population pharmacokinetics of tenofovir given as either tenofovir disoproxil fumarate or tenofovir alafenamide in an African population

Abstract Tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are prodrugs of the nucleotide analogue tenofovir, which acts intracellularly to inhibit HIV replication. Whereas TDF converts to tenofovir in plasma and may cause kidney and bone toxicity, TAF mostly converts to tenofovir intracellularly, so it can be administered at lower doses. TAF leads to lower tenofovir plasma concentrations and lower toxicity, but there are limited data on its use in Africa. We used data from 41 South African adults living with HIV from the ADVANCE trial and described, with a joint model, the population pharmacokinetics of tenofovir given as TAF or TDF. The TDF was modeled to appear in plasma as tenofovir with a simple first‐order process. Instead, two parallel pathways were used for a TAF dose: an estimated 32.4% quickly appeared as tenofovir into the systemic circulation with first‐order absorption, whereas the rest was sequestered intracellularly and released into the systemic circulation as tenofovir slowly. Once in plasma (from either TAF or TDF), tenofovir disposition followed two‐compartment kinetics and had a clearance of 44.7 L/h (40.2–49.5), for a typical 70‐kg individual. This semimechanistic model describes the population pharmacokinetics of tenofovir when dosed as either TDF or TAF in an African population living with HIV and can be used as a tool for exposure prediction in patients, and to simulate alternative regimes to inform further clinical trials

Predictors of suboptimal adherence to isoniazid preventive therapy among adolescents and children living with HIV.

This study identified factors associated with adherence to a 6-month isoniazid preventive therapy (IPT) course among adolescents and children living with HIV. Forty adolescents living with HIV and 48 primary caregivers of children living with HIV completed a Likert-based survey to measure respondent opinions regarding access to care, quality of care, preferred regimens, perceived stigma, and confidence in self-efficacy. Sociodemographic data were collected and adherence measured as the average of pill counts obtained while on IPT. The rates of suboptimal adherence (< 95% adherent) were 22.5% among adolescents and 37.5% among the children of primary caregivers. Univariate logistic regression was used to model the change in the odds of suboptimal adherence. Independent factors associated with suboptimal adherence among adolescents included age, education level, the cost of coming to clinic, stigma from community members, and two variables relating to self-efficacy. Among primary caregivers, child age, concerns about stigma, and location preference for meeting a community-health worker were associated with suboptimal adherence. To determine whether these combined factors contributed different information to the prediction of suboptimal adherence, a risk score containing these predictors was constructed for each group. The risk score had an AUC of 0.87 (95% CI: 0.76, 0.99) among adolescents and an AUC of 0.76 (95% CI: 0.62, 0.90), among primary caregivers suggesting that these variables may have complementary predictive utility. The heterogeneous scope and associations of these variables in different populations suggests that interventions aiming to increase optimal adherence will need to be tailored to specific populations and multifaceted in nature. Ideally interventions should address both long-established barriers to adherence such as cost of transportation to attend clinic and more nuanced psychosocial barriers such as perceived community stigma and confidence in self-efficacy

1498. Geographic differences in weight change on dolutegravir: a prospective cohort study

Background: People with HIV (PWH) on integrase inhibitors may be at increased risk of excess weight gain, but it is unclear if this risk is consistent across settings. Our study objective was to compare weight change over 48 weeks among PWH in Uganda and South Africa.Figure 1.Mean weight change (kg) over 48 weeks among DISCO participants overall (A), among men (B), and among women (C). Methods: The Population Effectiveness of Dolutegravir Implementation in Sub-Saharan Africa (DISCO) study is a prospective observational cohort of PWH in routine clinical care at public-sector HIV clinics in Uganda and South Africa. Inclusion criteria were as follows: PWH >18 years old, on NNRTI-based first-line ART for >6 months, and switched to tenofovir disoproxil fumarate, lamivudine, and dolutegravir) by clinic staff. We measured the primary outcomes of weight (in kilograms [kg]) and waist circumference (WC, in centimeters [cm]) at enrollment, 24 weeks, and 48 weeks after switch. The primary outcomes were (1) weight change (kg) and (2) change in WC (cm). We used a linear mixed-effect regression model, adjusted for age, sex, education, duration on ART, and the interaction of study site and visit, to estimate weight. Results: 428 individuals in Uganda and 387 in South Africa had data available. The mean weight change over 48 weeks was 0.6 kg [95% CI: 0.1-1.0] in Uganda compared to 2.9 kg [2.4-3.4] in South Africa (p< 0.001); men had significantly smaller mean weight changes than women did in both countries (Figure 1). After adjustment, PWH in South Africa gained significantly more weight than those in Uganda. In participants with available waist data (277 in Uganda and 402 in South Africa), the mean change in WC was significantly greater among those in South Africa (2.3 cm [1.4-3.2]) than those in Uganda (0.8 cm [0.0-1.5]) (p< 0.017). Conclusion: PWH in South Africa experienced greater weight gain than in Uganda, suggesting substantial heterogeneity in this risk across settings. Strategies to address obesity risk in PWH should account for regionality. Disclosures: W D Francois Venter, MD, FCP, PhD, Gilead Sciences: Grant/Research Support|South African Medical Research Council: Grant/Research Support|Unitaid: Grant/Research Support|USAID: Grant/Research Support|ViiV Healthcare: Grant/Research Support Mark J Siedner, MD, MPH, Viiv Healthcare: Grant/Research Suppor

Strengthening primary care for diabetes and hypertension in Eswatini: study protocol for a nationwide cluster-randomized controlled trial

Background: Diabetes and hypertension are increasingly important population health challenges in Eswatini. Prior to this project, healthcare for these conditions was primarily provided through physician-led teams at tertiary care facilities and accessed by only a small fraction of people living with diabetes or hypertension. This trial tests and evaluates two community-based healthcare service models implemented at the national level, which involve health care personnel at primary care facilities and utilize the country’s public sector community health worker cadre (the rural health motivators [RHMs]) to help generate demand for care. Methods: This study is a cluster-randomized controlled trial with two treatment arms and one control arm. The unit of randomization is a primary healthcare facility along with all RHMs (and their corresponding service areas) assigned to the facility. A total of 84 primary healthcare facilities were randomized in a 1:1:1 ratio to the three study arms. The first treatment arm implements differentiated service delivery (DSD) models at the clinic and community levels with the objective of improving treatment uptake and adherence among clients with diabetes or hypertension. In the second treatment arm, community distribution points (CDPs), which previously targeted clients living with human immunodeficiency virus, extend their services to clients with diabetes or hypertension by allowing them to pick up medications and obtain routine nurse-led follow-up visits in their community rather than at the healthcare facility. In both treatment arms, RHMs visit households regularly, screen clients at risk, provide personalized counseling, and refer clients to either primary care clinics or the nearest CDP. In the control arm, primary care clinics provide diabetes and hypertension care services but without the involvement of RHMs and the implementation of DSD models or CDPs. The primary endpoints are mean glycated hemoglobin (HbA1c) and systolic blood pressure among adults aged 40 years and older living with diabetes or hypertension, respectively. These endpoints will be assessed through a household survey in the RHM service areas. In addition to the health impact evaluation, we will conduct studies on cost-effectiveness, syndemics, and the intervention’s implementation processes. Discussion: This study has the ambition to assist the Eswatini government in selecting the most effective delivery model for diabetes and hypertension care. The evidence generated with this national-level cluster-randomized controlled trial may also prove useful to policy makers in the wider Sub-Saharan African region. Trial registration: NCT04183413. Trial registration date: December 3, 201