A packaged intervention to improve viral load monitoring within a deeply rural health district of South Africa.

BACKGROUND: The KwaZulu-Natal (KZN) province of South Africa has the highest prevalence of HIV infection in the world. Viral load (VL) testing is a crucial tool for clinical and programmatic monitoring. Within uMkhanyakude district, VL suppression rates were 91% among patients with VL data; however, VL performance rates averaged only 38·7%. The objective of this study was to determine if enhanced clinic processes and community outreach could improve VL monitoring within this district. METHODS: A packaged intervention was implemented at three rural clinics in the setting of the KZN HIV AIDS Drug Resistance Surveillance Study. This included file hygiene, outreach, a VL register and documentation revisions. Chart audits were used to assess fidelity. Outcome measures included percentage VL performed and suppressed. Each rural clinic was matched with a peri-urban clinic for comparison before and after the start of each phase of the intervention. Monthly sample proportions were modelled using quasi-likelihood regression methods for over-dispersed binomial data. RESULTS: Mkuze and Jozini clinics increased VL performance overall from 33·9% and 35·3% to 75·8% and 72·4%, respectively which was significantly greater than the increases in the comparison clinics (RR 1·86 and 1·68, p < 0·01). VL suppression rates similarly increased overall by 39·3% and 36·2% (RR 1·84 and 1·70, p < 0·01). The Chart Intervention phase showed significant increases in fidelity 16 months after implementation. CONCLUSIONS: The packaged intervention improved VL performance and suppression rates overall but was significant in Mkuze and Jozini. Larger sustained efforts will be needed to have a similar impact throughout the province.

Depression and all-cause mortality risk in HIV-infected and HIV-uninfected US veterans: a cohort study.

OBJECTIVES: The contribution of depression to mortality in adults with and without HIV infection is unclear. We hypothesized that depression increases mortality risk and that this association is stronger among those with HIV infection. METHODS: Veterans Aging Cohort Study (VACS) data were analysed from the first clinic visit on or after 1 April 2003 (baseline) to 30 September 2015. Depression definitions were: (1) major depressive disorder defined using International Classification of Diseases, Ninth Revision (ICD-9) codes; (2) depressive symptoms defined as Patient Health Questionnaire (PHQ)-9 scores ≥ 10. The outcome was all-cause mortality. Covariates were demographics, comorbid conditions and health behaviours. RESULTS: Among 129 140 eligible participants, 30% had HIV infection, 16% had a major depressive disorder diagnosis, and 24% died over a median follow-up time of 11 years. The death rate was 25.3 [95% confidence interval (CI) 25.0-25.6] deaths per 1000 person-years. Major depressive disorder was associated with mortality [hazard ratio (HR) 1.04; 95% CI 1.01, 1.07]. This association was modified by HIV status (interaction P-value = 0.02). In HIV-stratified analyses, depression was significantly associated with mortality among HIV-uninfected veterans but not among those with HIV infection. Among those with PHQ-9 data (n = 7372), 50% had HIV infection, 22% had PHQ-9 scores ≥ 10, and 28% died over a median follow-up time of 12 years. The death rate was 27.3 (95% CI 26.1-28.5) per 1000 person-years. Depressive symptoms were associated with mortality (HR 1.16; 95% CI 1.04, 1.28). This association was modified by HIV status (interaction P-value = 0.05). In HIV-stratified analyses, depressive symptoms were significantly associated with mortality among veterans with HIV infection but not among those without HIV infection. CONCLUSIONS: Depression was associated with all-cause mortality. This association was modified by HIV status and method of depression ascertainment.

Characteristics of TB cases without documented sputum culture in the United States, 2011-2021.

Culture-based diagnostics are the gold standard for diagnosing pulmonary TB (PTB). We characterized culture practices by comparing cases with documented sputum culture to those without.Using multivariable logistic regression, we examined associations between PTB case characteristics and no documented sputum culture reported to the U.S. National TB Surveillance System during 2011-2021.Among 69,538 PTB cases analyzed, no sputum culture attempt was documented for 5,869 (8%). Non-sputum culture specimens were documented for 54%, 80%, and 89% of cases without documented sputum culture attempts among persons aged <15 years, 15-64, and 65+ years, respectively; bronchial fluid and lung tissue were common non-sputum specimens among cases in persons >15 years old. Having no documented sputum culture was associated with age <15 years (aOR 23.84, 99% CI 20.09-28.27) or ≥65 years (aOR 1.22, 99% CI 1.07-1.39), culture of a non-sputum specimen (aOR 6.57, 99% CI 5.93-7.28), residence in a long-term care facility (aOR 1.58, 99% CI 1.23-2.01), and receiving TB care outside of a health department (aOR 1.79, 99% CI 1.61-1.98).Inability to obtain sputum from children and higher diagnostic suspicion for disease processes that require tissue-based diagnostics could explain these findings..

Depression: an individual-level early warning indicator of virologic failure in HIV patients in South Africa.

OBJECTIVE: To identify individual-level early warning indicators of virologic failure in HIV patients receiving antiretroviral therapy (ART) in South Africa. DESIGN: A matched case-control study of individuals with and without virologic failure (VF) (>5 months on ART and HIV-1 plasma viral load >1,000 copies/mL) was conducted between June 2014 and June 2018. Of the 1,000 participants enrolled in the parent cohort, 96 experienced VF, and 199 additional controls were identified from the parent cohort and matched 1:2 (some matched 1:3) for sex, age, ART duration, and site. Participants were interviewed while clinical, pharmacy refill, laboratory, and objective pharmacological data were obtained. Multivariate conditional logistic regression models were constructed using model selection to identify factors associated with VF. Significant determinants of VF were identified using an alpha level of 0.05. RESULTS: In a full conditional model, higher cumulative ART adherence, quantified using tenofovir-diphosphate concentrations in dried blood spots (OR 0.26) and medication possession ratio (OR 0.98) were protective against VF, whereas an increase in total depression score (OR 1.20) was predictive of VF. CONCLUSION: This analysis demonstrates the importance of depression as a key individual-level early warning indicator of VF. Efforts to address mental health concerns among patients with people living with HIV could improve virologic suppression.

OBJECTIF: Identifier les indicateurs d'alerte précoce au niveau individuel de l'échec virologique chez les patients séropositifs recevant un traitement antirétroviral (TAR) en Afrique du Sud. MÉTHODE: Une étude cas-témoins appariée de personnes avec et sans échec virologique (FV, pour l'anglais « virologic failure ¼) (>5 mois sous ART et charge virale plasmatique du VIH-1 >1 000 copies/ml) a été menée entre juin 2014 et juin 2018. Sur les 1 000 participants inscrits dans la cohorte parente, 96 ont présenté une FV et 199 témoins supplémentaires ont été identifiés dans la cohorte parentale et appariés 1:2 (certains appariés 1:3) pour le sexe, l'âge, la durée du TAR et le site. Les participants ont été interrogés pendant que des données cliniques, de renouvellement de pharmacie, de laboratoire et pharmacologiques objectives ont été obtenues. Des modèles de régression logistique conditionnelle multivariée ont été construits à l'aide d'une sélection de modèles pour identifier les facteurs associés à la FV. Les déterminants significatifs de la FV ont été identifiés à l'aide d'un niveau alpha de 0,05. RÉSULTATS: Dans un modèle conditionnel complet, une observance cumulative plus élevée du TAR, quantifiée à l'aide des concentrations de ténofovir-diphosphate dans les gouttes de sang séché (OR 0,26) et du ratio de possession de médicaments (OR 0,98) protégeait contre la FV, tandis qu'une augmentation du score de dépression totale (OR 1,20) était prédictive de la FV. CONCLUSION: Cette analyse démontre l'importance de la dépression en tant qu'indicateur précoce clé au niveau individuel de la FV. Les efforts visant à résoudre les problèmes de santé mentale chez les personnes vivant avec le VIH pourraient améliorer la suppression virologique.

From Silos to Solidarity: Case Study of a Patient-Centered, Integrative Approach to Opioid Tapering and Chronic Pain Mitigation in a Multidisciplinary AIDS Clinic.

BACKGROUND: People with HIV (PWH) are at a disproportionate risk for experiencing both chronic pain and opioid use disorder (OUD). Prescription opioid tapering is typically addressed within the "silo model" of medical care, whereby attention is focused solely on opioid addiction rather than also addressing chronic pain management, and limited communication occurs between patient and providers. OBJECTIVE: This descriptive case study examined an integrative, collaborative care model consisting of Provider, Physical Therapist (PT), and Patient aimed at decreasing chronic pain and opioid use within a multidisciplinary HIV/AIDS clinic. METHOD: A physical-therapy based model of chronic pain mitigation and physician-driven opioid tapering was implemented. The Provider, PT, and Patient worked collaboratively to address physiological pain, pain coping skills and opioid tapering. A patient case example was used to illustrate the implementation of the model for a future, larger study in the same patient population. RESULTS: This model was feasible in this case example in terms of clinic workflow and acceptability to both the Patient and Providers in this clinic. After the intervention, the Patient's pain was fully eliminated, and he had ceased all opioid use. CONCLUSION: Results of this case study suggest that utilizing an integrative, patient-centered approach to both chronic pain management and opioid tapering may be feasible within the context of a multidisciplinary HIV/AIDS clinic. Generalizability is limited by case study model; however, this gives insight into the value of a collaborative alternative compared to a "silo" model of opioid tapering and chronic pain management in preparation for a larger study.

A nurse-led intervention to improve management of virological failure in public sector HIV clinics in Durban, South Africa: A pre- and post-implementation evaluation.

BACKGROUND: Identification of patients on antiretroviral therapy (ART) with virological failure (VF) and the response in the public health sector remain significant challenges. We previously reported improvement in routine viral load (VL) monitoring after ART commencement through a health system-strengthening, nurse-led 'VL champion' programme as part of a multidisciplinary team in three public sector clinics in Durban, South Africa. OBJECTIVES: To report on the impact of the VL champion model adapted to identify, support and co-ordinate the management of individuals with VF on first-line ART in a setting with limited electronic-based record capacity. METHODS: We evaluated the VL champion model using a controlled before-after study design. A paper-based tool, the 'high VL register', was piloted under the supervision of the VL champion to improve data management, monitoring of counselling support, and enacting of clinical decisions. We abstracted chart and electronic data (TIER.net) for eligible individuals with VF in the year before and after implementation of the programme, and compared outcomes for individuals during these periods. Our primary outcome was successful completion of the VF pathway, defined as a repeat VL <1 000 copies/mL or a change to second-line ART within 6 months of VF. In a secondary analysis, we assessed the completion of each step in the pathway. RESULTS: We identified 60 and 56 individuals in the pre-intervention and post-intervention periods, respectively, with VF who met the inclusion criteria. Sociodemographic and clinical characteristics were similar between the periods. Repeat VL testing was completed in 61.7% and 57.8% of individuals in these two groups, respectively. We found no difference in the proportion achieving our primary outcome in the pre- and post-intervention periods: 11/60 (18.3%; 95% confidence interval (CI) 9 - 28) and 15/56 (22.8%; 95% CI 15 - 38), respectively (p=0.28). In multivariable logistic regression models adjusted for potential confounding factors, individuals in the post-intervention period had a non-significant doubling of the odds of achieving the primary outcome (adjusted odds ratio 2.07; 95% CI 0.75 - 5.72). However, there was no difference in the rates of completion of each step along the first-line VF cascade of care. CONCLUSIONS: This enhanced intervention to improve VF in the public sector using a paper-based data management system failed to achieve significant improvements in first-line VF management over the standard of care. In addition to interventions that better address patient-centred factors that contribute to VF, we believe that there are substantial limitations to and staffing requirements involved in the ongoing utilisation of a paper-based tool. A prioritisation is needed to further expand and upgrade the electronic medical record system with capabilities for prompting staff regarding patients with missed visits and critical laboratory results demonstrating VF.

Comparative analyses of published cost effectiveness models highlight critical considerations which are useful to inform development of new models.

Background: Comparative analyses of published cost effectiveness models provide useful insights into critical issues to inform the development of new cost effectiveness models in the same disease area.Objective: The purpose of this study was to describe a comparative analysis of cost-effectiveness models and highlight the importance of such work in informing development of new models. This research uses genotypic antiretroviral resistance testing after first line treatment failure for Human Immunodeficiency Virus (HIV) as an example.Method: A literature search was performed, and published cost effectiveness models were selected according to predetermined eligibility criteria. A comprehensive comparative analysis was undertaken for all aspects of the models.Results: Five published models were compared, and several critical issues were identified for consideration when developing a new model. These include the comparator, time horizon and scope of the model. In addition, the composite effect of drug resistance prevalence, antiretroviral therapy efficacy, test performance and the proportion of patients switching to second-line ART potentially have a measurable effect on model results. When considering CD4 count and viral load, dichotomizing patients according to higher cost and lower quality of life (AIDS) versus lower cost and higher quality of life (non-AIDS) status will potentially capture differences between resistance testing and other strategies, which could be confirmed by cross-validation/convergent validation. A quality adjusted life year is an essential outcome which should be explicitly explored in probabilistic sensitivity analysis, where possible.Conclusions: Using an example of GART for HIV, this study demonstrates comparative analysis of previously published cost effectiveness models yields critical information which can be used to inform the structure and specifications of new models.

Targeting the third '90': introducing the viral load champion.

Objective: To move closer to achieving the third target of the UNAIDS 90-90-90 goals, we prospectively implemented a viral load (VL) champion (VLC) program aimed at enhancing VL monitoring and recognition of treatment failure. Design: Three clinics in eThekwini, Kwa-Zulu Natal (low-, medium- and high-volume, encompassing 9184 patients overall) were each assigned a VLC. We employed a descriptive analysis (chart audit) to compare the pre-intervention period to a 1-year post-intervention period. The number of patients with a VL test performed 6 and 12 months after the intervention was calculated as a proportion of VL tests due at those time points (VL completion rate). Results: The pre-implementation VL completion rate at the three sites was respectively 68% (140/205 patients), 54% (84/155 patients) and 64% (323/504 patients), and the 6-month post-implementation completion rate increased to 83% (995/1194 patients), 90% (793/878 patients) and 99% (3101/3124 patients) (P < 0.0001 for each site). VL completion rates remained significantly higher at 12 months post-implementation, with an average cumulative VL completion rate of >90% across all facilities. Conclusion: We demonstrate a successful, multifaceted, quality-improvement intervention centered on a clinic-level VLC which, taken to scale, has important implications for attaining the third UNAIDS 90-90-90 target.

Objectif : Dans le but de se rapprocher de l'atteinte de la troisième cible des objectifs 90-90-90 du Programme commun des Nations Unies sur le VIH/Sida (ONUSIDA), nous avons prospectivement mis en œuvre un programme « champion de la charge virale ¼ (VLC) visant à améliorer le suivi de la charge virale (VL) et la reconnaissance de l'échec du traitement.Schéma : Trois centres à eThekwini, Kwa-Zulu Natal (volume faible, moyen et élevé, soit 9184 patients au total), ont été chacun affectés au VLC. Nous employons une analyse descriptive (audit de dossiers) afin de comparer la période avant l'intervention à la période d'un an qui a suivi l'intervention. Le nombre de patients ayant eu un test VL 6 et 12 mois après l'intervention a été calculé comme une proportion de test VL exigibles à ces dates respectivement (taux d'achèvement du VL).Résultats : Le taux d'achèvement du VL avant la mise en route dans trois sites a été de 68% (140/205 patients), 54% (84/155 patients) et 64% (323/504 patients), respectivement, et le taux d'achèvement à 6 mois après la mise en œuvre a augmenté à 83% (995/1194 patients), 90% (793/878 patients) et 99% (3101/3124 patients), respectivement (P < 0,0001 pour chaque site). Les taux d'achèvement du VL sont restés significativement plus élevés à 12 mois après la mise en œuvre, avec un taux cumulé moyen du VL >90% dans toutes les structures.Conclusion : Nous avons montré la qualité d'une intervention d'amélioration réussie à multiples facettes, centrée sur le VLC au niveau des centres qui­à plus grande échelle­a des implications majeures pour l'atteinte de la troisième cible 90-90-90 de l'ONUSIDA.

Objetivo: Con el propósito de avanzar hacia el cumplimiento del tercer elemento del objetivo «90-90-90¼ del Programa Conjunto de las Naciones Unidas sobre el VIH/SIDA (ONUSIDA), se introdujo un programa con un promotor del seguimiento de la viremia, encaminado a reforzar la vigilancia de la concentración vírica y el reconocimiento del fracaso terapéutico.Método: En cada uno de tres consultorios de eThekwini, en Kwa-Zulu Natal (con una carga asistencial baja, intermedia y alta, que cubrían un total de 9184 pacientes) se nombró un promotor del seguimiento de la viremia. Mediante un análisis descriptivo, se comparó el período preintervención con un período posintervención de un año. El número de pacientes en quienes se practicó la viremia a los 6 y 12 meses después de la intervención se calculó como la proporción de las viremias previstas en estos puntos temporales (tasa de compleción de la viremia).Resultados: La tasa de compleción de la viremia en los tres centros fue como sigue: 68% (140/205 pacientes), 54% (84/155 pacientes) y 64% (323/504 pacientes) y a los 6 meses posintervención, esta tasa aumentó respectivamente a 83% (995/1194 pacientes), 90% (793/878 pacientes) y 99% (3101/3124 pacientes) (P < 0,0001 para cada centro). Las tasas de compleción de la viremia permanecieron significativamente más altas a los 12 meses posintervención con una tasa acumulada superior al 90% en todos los establecimientos.Conclusión: Se puso en evidencia una intervención polifacética eficaz de mejoramiento de la calidad centrada en un promotor clínico del seguimiento de la viremia en cada consultorio, cuya aplicación en una escala más amplia, tendría importantes repercusiones en favor del cumplimiento del tercer elemento del objetivo «90-90-90¼ del ONUSIDA.