HIV viral suppression and longevity among a cohort of children initiating antiretroviral therapy in Eastern Cape,South Africa

Introduction

There are limited data on viral suppression (VS) in children with HIV receiving antiretroviral therapy (ART) in routine care in low‐resource settings. We examined VS in a cohort of children initiating ART in routine HIV care in Eastern Cape Province, South Africa.

Methods

The Pediatric Enhanced Surveillance Study enrolled HIV‐infected ART eligibility children zero to twelve years at five health facilities from 2012 to 2014. All children received routine HIV care and treatment services and attended quarterly study visits for up to 24 months. Time to VS among those starting treatment was measured from ART start date to first viral load (VL) result <1000 and VL <50 copies/mL using competing risk estimators (death as competing risk). Multivariable sub‐distributional hazards models examined characteristics associated with VS and VL rebound following suppression among those with a VL >30 days after the VS date.

Results

Of 397 children enrolled, 349 (87.9%) started ART: 118 (33.8%) children age <12 months, 122 (35.0%) one to five years and 109 (31.2%) six to twelve years. At study enrolment, median weight‐for‐age z‐score (WAZ) was −1.7 (interquartile range (IQR):−3.1 to −0.4) and median log VL was 5.6 (IQR: 5.0 to 6.2). Cumulative incidence of VS <1000 copies/mL at six, twelve and twenty‐four months was 57.6% (95% CI 52.1 to 62.7), 78.7% (95% CI 73.7 to 82.9) and 84.0% (95% CI 78.9 to 87.9); for VS <50 copies/mL: 40.3% (95% CI 35.0 to 45.5), 63.9% (95% CI 58.2 to 69.0) and 72.9% (95% CI 66.9 to 78.0). At 12 months only 46.6% (95% CI 36.6 to 56.0) of children <12 months had achieved VS <50 copies/mL compared to 76.9% (95% CI 67.9 to 83.7) of children six to twelve years (p < 0.001). In multivariable models, children with VL >1 million copies/mL at ART initiation were half as likely to achieve VS <50 copies/mL (adjusted sub‐distributional hazards 0.50; 95% CI 0.36 to 0.71). Among children achieving VS <50 copies/mL, 37 (19.7%) had VL 50 to 1000 copies/mL and 31 (16.5%) had a VL >1000 copies/mL. Children <12 months had twofold increased risk of VL rebound to VL >1000 copies/mL (adjusted relative risk 2.03, 95% CI: 1.10 to 3.74) compared with six to twelve year olds.

Conclusions

We found suboptimal VS among South African children initiating treatment and high proportions experiencing VL rebound, particularly among younger children. Greater efforts are needed to ensure that all children achieve optimal outcomes.

     

Long-term usage patterns and clinical outcomes in a community-based differentiated antiretroviral therapy delivery programme in South Africa

Introduction

There is little data on long-term implementation and outcomes for people living with HIV (PLHIV) in differentiated antiretroviral therapy (ART) delivery programmes. We aimed to analyse usage patterns of and associated treatment outcomes in a community ART programme, within the Centralized Chronic Medicines Dispensing and Distribution programme, in South Africa over 3.5 years.

Methods

We performed a retrospective cohort study among PLHIV on first-line ART who were eligible for community ART delivery between October 2016 and March 2019, from 56 urban clinics in KwaZulu-Natal, South Africa. Follow-up ended in March 2020. We measured referral rates and, among those referred, we characterized patterns of community ART usage using group-based trajectory modelling following referral. We used survival analysis to measure the association between community ART usage and loss-to-care (no visit for ≥365 days) and logistic regression to measure the association between community ART usage and viraemia (≥50 copies/ml).

Results

Among the 80,801 patients eligible for community ART, the median age was 36 years, 69.8% were female and the median (interquartile range [IQR]) follow-up time was 22 (13–31) months. In total, 49,961 (61.8%) were referred after a median of 6 (IQR 2–13) months from first eligibility. After referral, time spent in community ART varied; 42% remained consistently in community ART, 15% returned to consistent clinic-based care and the remaining 43% oscillated between community ART and clinic-based care. Following referral, the incidence of loss-to-care was 3.93 (95% confidence interval [CI]: 3.71–4.15) per 100 person-years during periods of community ART usage compared to 5.75 (95% CI: 5.28–6.25) during clinic-based care. In multivariable models, community ART usage was associated with a 36% reduction in the hazards of loss-to-care (adjusted hazard ratio: 0.64 [95% CI: 0.57–0.72]). The proportion of patients who became viraemic after first community ART referral was 5.2% and a 10% increase in time in community ART was associated with a 3% reduction in odds of viraemia (adjusted odds ratio: 0.97 [95% CI: 0.95–0.99]).

Conclusions

Community ART usage patterns vary considerably, while clinical outcomes were good. Promoting consistent community ART usage may reduce clinic burden and the likelihood of patients being lost to care, while sustaining viral suppression.     

Risk factors for mortality during antiretroviral therapy in older populations in resource-limited settings

Introduction

An increasing proportion of adult patients initiating antiretroviral therapy (ART) in resource-limited settings are aged >50 years. Older populations on ART appear to have heightened risk of death, but little is known about factors influencing mortality in this population.

Methods

We performed a retrospective observational multisite cohort study including all adult patients (≥15 years) initiating ART between 2003 and 2013 in programmes supported by Médecins Sans Frontières across 12 countries in Asia, Africa and Europe. Patients were stratified into two age groups, >50 years and 15 to 50 years. A Cox proportional hazards model was used to explore factors associated with mortality.

Results

The study included 41,088 patients: 2591 (6.3%) were aged >50 years and 38,497 (93.7%) were aged 15 to 50 years. The mortality rate was significantly higher in the age group >50 years [367 (14.2%) deaths; mortality rate 7.67 deaths per 100 person-years (95% confidence interval, CI: 6.93 to 8.50)] compared to the age group 15 to 50 years [3788 (9.8%) deaths; mortality rate 4.18 deaths per 100 person-years (95% CI: 4.05 to 4.31)], p<0.0001. Higher CD4 levels at baseline were associated with significantly reduced mortality rates in the 15 to 50 age group but this association was not seen in the >50 age group. WHO Stage 4 conditions were more strongly associated with increased mortality rates in the 15 to 50 age group compared to populations >50 years. WHO Stage 3 conditions were associated with an increased mortality rate in the 15 to 50 age group but not in the >50 age group. Programme region did not affect mortality rates in the >50 age group; however being in an Asian programme was associated with a 36% reduced mortality rate in populations aged 15 to 50 years compared to being in an African programme. There was a higher overall incidence of Stage 3 WHO conditions in people >50 years (12.8/100 person-years) compared to those 15 to 50 years (8.1/100 person-years) (p<0.01). The rate of Stage 4 WHO conditions was similar (5.8/100 versus 6.1/100 respectively, p=0.52). Mortality rates on ART associated with the majority of specific WHO conditions were similar between the 15 to 50 and >50 age groups.

Conclusions

Older patients on ART in resource-limited settings have increased mortality rates, but compared to younger populations this appears to be less influenced by baseline CD4 count and WHO clinical stage. HIV treatment programmes in resource-limited settings need to consider risk factors associated with mortality on ART in older populations, which may differ to those related to younger adults.     

Predictors of mortality in patients initiating antiretroviral therapy in Durban, South Africa.

OBJECTIVE: To identify predictors of mortality in patients initiating antiretroviral therapy (ART) in Durban, South Africa. DESIGN: We conducted a retrospective cohort study analyzing data on patients who presented to McCord Hospital, Durban, and started ART between 1 January 1999 and 29 February 2004. We performed univariate and multivariate analysis and constructed Kaplan-Meier curves to assess predictors. RESULTS: Three hundred and nine patients were included. Forty-nine (16%) had died by the conclusion of the study. In univariate analysis, the strongest predictors of mortality were a CD4 cell count<50/microl (hazard ratio (HR) 3.70, 95% confidence interval (CI) 1.96-7.14), a haemoglobin concentration相似文献   

Adherence to antiretroviral therapy for HIV in sub‐Saharan Africa and Asia: a comparative analysis of two regional cohorts

Introduction : Our understanding of how to achieve optimal long‐term adherence to antiretroviral therapy (ART) in settings where the burden of HIV disease is highest remains limited. We compared levels and determinants of adherence over time between HIV‐positive persons receiving ART who were enrolled in a bi‐regional cohort in sub‐Saharan Africa and Asia. Methods : This multicentre prospective study of adults starting first‐line ART assessed patient‐reported adherence at follow‐up clinic visits using a 30‐day visual analogue scale. Determinants of suboptimal adherence (<95%) were assessed for six‐month intervals, using generalized estimating equations multivariable logistic regression with multiple imputations. Region of residence (Africa vs. Asia) was assessed as a potential effect modifier. Results : Of 13,001 adherence assessments in 3934 participants during the first 24 months of ART, 6.4% (837) were suboptimal, with 7.3% (619/8484) in the African cohort versus 4.8% (218/4517) in the Asian cohort (p < 0.001). In the African cohort, determinants of suboptimal adherence were male sex (odds ratio (OR) 1.27, 95% confidence interval (CI) 1.06–1.53; p = 0.009), younger age (OR 0.8 per 10 year increase; 0.8–0.9; p = 0.003), use of concomitant medication (OR 1.8, 1.0–3.2; p = 0.044) and attending a public facility (OR 1.3, 95% CI 1.1–1.7; p = 0.004). In the Asian cohort, adherence was higher in men who have sex with men (OR for suboptimal adherence 0.6, 95% CI 0.4–0.9; p = 0.029) and lower in injecting drug users (OR for suboptimal adherence 1.6, 95% CI 0.9–2.6; p = 0.075), compared to heterosexuals. Risk of suboptimal adherence decreased with longer ART duration in both regions. Participants in low‐ and lower‐middle‐income countries had a higher risk of suboptimal adherence (OR 1.6, 1.3–2.0; p < 0.001), compared to those in upper‐middle or high‐income countries. Suboptimal adherence was strongly associated with virological failure, in Africa (OR 5.8, 95% CI 4.3–7.7; p < 0.001) and Asia (OR 9.0, 95% CI 5.0–16.2; p < 0.001). Patient‐reported adherence barriers among African participants included scheduling demands, drug stockouts, forgetfulness, sickness or adverse events, stigma or depression, regimen complexity and pill burden. Conclusions : Psychosocial factors and health system resources may explain regional differences. Adherence‐enhancing interventions should address patient‐reported barriers tailored to local settings, prioritizing the first years of ART.     

Health outcomes among HIV-positive Latinos initiating antiretroviral therapy in North America versus Central and South America

Introduction

Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America.

Methods

HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts.

Results

The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p<0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57).

Conclusions

HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation.     

Universal test and treat is not associated with sub‐optimal antiretroviral therapy adherence in rural South Africa: the ANRS 12249 TasP trial

Introduction

HIV treatment guidelines now recommend antiretroviral therapy (ART) initiation regardless of CD4 count to maximize benefit both for the individual and society. It is unknown whether the initiation of ART at higher CD4 counts would affect adherence levels. We investigated whether initiating ART at higher CD4 counts was associated with sub‐optimal adherence (<95%) during the first 12 months of ART.

Methods

A prospective cohort study nested within a two‐arm cluster‐randomized trial of universal test and treat was implemented from March 2012 to June 2016 to measure the impact of ART on HIV incidence in rural KwaZulu‐Natal. ART was initiated regardless of CD4 count in the intervention arm and according to national guidelines in the control arm. ART adherence was measured monthly using a visual analogue scale (VAS) and pill counts (PC). HIV viral load was measured at ART initiation, three and six months, and six‐monthly thereafter. We pooled data from participants in both arms and used random‐effects logistic regression models to examine the association between CD4 count at ART initiation and sub‐optimal adherence, and assessed if adherence levels were associated with virological suppression.

Results

Among 900 individuals who initiated ART ≥12 months before study end, median (IQR) CD4 at ART initiation was 350 cells/mm³ (234, 503); median age was 34.6 years (IQR 27.4 to 46.4) and 71.7% were female. Adherence was sub‐optimal in 14.7% of visits as measured by VAS and 20.7% by PC. In both the crude analyses and after adjusting for potential confounders, adherence was not significantly associated with CD4 count at ART initiation (adjusted OR for linear trend in sub‐optimal adherence with every 100 cells/mm³ increase in CD4 count: 1.00, 95% CI 0.95 to 1.05, for VAS, and 1.03, 95% CI 0.99 to 1.07, for PC). Virological suppression at 12 months was 97%. Optimal adherence by both measures was significantly associated with virological suppression (p < 0.001 for VAS; p = 0.006 for PC).

Conclusions

We found no evidence that higher CD4 counts at ART initiation were associated with sub‐optimal ART adherence in the first 12 months. Our findings should alleviate concerns about adherence in individuals initiating ART at higher CD4 counts, however long‐term outcomes are needed. ClinicalTrials.gov NCT01509508.

     

Mental health,substance use and viral suppression in adolescents receiving ART at a paediatric HIV clinic in South Africa

IntroductionMental health problems are prevalent in adolescents living with HIV (ALHIV), often remain untreated, and may negatively affect antiretroviral therapy (ART) adherence and viral suppression. We implemented routine mental health screening at a paediatric ART clinic to improve the identification and management of mental health problems in ALHIV. In this report, we examine screening outcomes, associated patient characteristics and the odds of unsuppressed viral load in ALHIV screening positive for mental disorders.MethodsAdolescents aged 10 to 19 years attending Rahima Moosa Hospital in Johannesburg, South Africa between February 1, 2018, and January 1, 2020, were offered mental health screening at each routine HIV care visit. The screening included four pre‐screening questions followed by full screening (conditional on positive pre‐screening) for depression (Patient Health Questionnaire‐9 [PHQ‐9]), suicide (Adolescent Innovations Project [AIP]‐handbook), anxiety (Generalized Anxiety Disorder‐7 [GAD‐7]), post‐traumatic stress disorder (PTSD) (Primary Care PTSD Screen [PC‐PTSD‐5]) and substance use (CAGE Adapted to Include Drugs [CAGE‐AID]). We assessed screening outcomes and calculated adjusted odds ratios for associations between positive screening tests at the first screen and unsuppressed viral load (>400 copies/mL) at the measurement taken closest to the date of screening, within hundred days before and one day after screening.ResultsOut of 1203 adolescents who attended the clinic, 1088 (90.4%) were pre‐screened of whom 381 (35.0%) underwent full screening, 48 (4.4%) screened positive for depression (PHQ‐9 ≥10), 29 (2.8%) for suicidal concern, 24 (2.2%) for anxiety (GAD‐7 ≥10), 38 (3.2%) for PTSD (PC‐PTSD‐5 ≥3), 18 (1.7%) for substance use (CAGE‐AID ≥2) and 97 (8.9%) for any of these conditions. Positive screening for depression (aOR 2.39, 95% CI 1.02 to 5.62), PTSD (aOR 3.18, 95% CI 1.11 to 9.07), substance use (aOR 7.13, 95% CI 1.60 to 31.86), or any condition (aOR 2.17, 95% CI 1.17 to 4.02) were strongly associated with unsuppressed viral load.ConclusionsALHIV affected by mental health problems have increased rates of unsuppressed viral load and need specific clinical attention. The integration of routine mental health screening in paediatric ART programmes is a feasible approach for identifying and referring adolescents with mental health and adherence problems to counselling and psychosocial support services and if needed to psychiatric care.     

Progressive improvement in short‐, medium‐ and long‐term graft survival in kidney transplantation patients in Ireland – a retrospective study

It is often quoted that while short‐term graft survival in kidney transplantation has improved in recent years, it has not translated into a commensurate improvement in long‐term graft survival. We considered whether this was true of the entire experience of the national kidney transplant program in Ireland. A retrospective analysis of the National Kidney Transplant Service (NKTS) database was undertaken to investigate patient and graft survival for all adult first deceased donor kidney transplant recipients in Ireland, 1971–2015. Three thousand two hundred and sixty recipients were included in this study. Kaplan–Meier methods were used to estimate survival at each time period post transplant for the various eras of transplantation. Uncensored graft survival has improved over the course of the program in Ireland at various time points despite risk factors for graft failure progressively increasing over successive eras. For example the graft survival at 15 years post transplant has increased from 10% in 1971–1975 to 45% by 1996–2000. Ireland has experienced a progressive improvement in long‐term graft survival following kidney transplantation. Whether these trends are attributable to biological or nonbiological factors is unclear but likely involves a combination of both.