How community ART delivery may improve HIV treatment outcomes: Qualitative inquiry into mechanisms of effect in a randomized trial of community‐based ART initiation,monitoring and re‐supply (DO ART) in South Africa and Uganda

IntroductionUNAIDS fast track targets for ending the AIDS epidemic by 2030 call for viral suppression in 95% of people using antiretroviral therapy (ART) to treat HIV infection. Difficulties in linking to care following a positive HIV test have impeded progress towards meeting treatment targets. Community‐based HIV services may reduce linkage barriers and have been associated with high retention and favourable clinical outcomes. We use qualitative data from The Delivery Optimization of Antiretroviral Therapy (DO ART) Study, a three‐arm randomized trial of community ART initiation, monitoring and re‐supply conducted in western Uganda and KwaZulu‐Natal South Africa, to identify mechanisms through which community ART delivery may improve treatment outcomes, defined as viral suppression in people living with HIV (PLHIV).MethodsWe conducted open‐ended interviews with a purposeful sample of 150 DO ART participants across study arms and study sites, from October 2016 to November 2019. Interviews covered experiences of: (1) HIV testing; (2) initiating and refilling ART; and (3) participating in the DO ART Study. A combined inductive content analytic and thematic approach was used to characterize mechanisms through which community delivery of ART may have contributed to viral suppression in the DO ART trial.ResultsThe analysis yielded four potential mechanisms drawn from qualitative data representing the perspectives and priorities of DO ART participants. Empowering participants to schedule, re‐schedule and select the locations of community‐based visits via easy phone contact with clinical staff is characterized as flexibility. Integration refers to combining the components of clinic‐based visits into single interaction with a healthcare provider. Providers” willingness to talk at length with participants during visits, addressing non‐HIV as well as HIV‐related concerns, is termed “a slower pace”. Finally, increased efficiency denotes the time savings and increased income‐generating opportunities for participants brought about by delivering services in the community.ConclusionsUnderstanding the mechanisms through which HIV service delivery innovations produce an effect is key to transferability and potential scale‐up. The perspectives and priorities of PLHIV can indicate actionable changes for HIV care programs that may increase engagement in care and improve treatment outcomes.     

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.     

Adolescent pregnancy at antiretroviral therapy (ART) initiation: a critical barrier to retention on ART

Introduction

Adolescence and pregnancy are potential risk factors for loss to follow‐up (LTFU) while on antiretroviral therapy (ART). We compared adolescent and adult LTFU after ART initiation to quantify the impact of age, pregnancy, and site‐level factors on LTFU.

Methods

We used routine clinical data for patients initiating ART as young adolescents (YA; 10 to 14 years), older adolescents (OA; 15 to 19 years) and adults (≥20 years) from 2000 to 2014 at 52 health facilities affiliated with the International epidemiology Databases to Evaluate AIDS (IeDEA) East Africa collaboration. We estimated cumulative incidence (95% confidence interval, CI) of LTFU (no clinic visit for ≥6 months after ART initiation) and identified patient and site‐level correlates of LTFU, using multivariable Cox proportional hazards models for all patients as well as individual age groups.

Results

A total of 138,387 patients initiated ART, including 2496 YA, 2955 OA and 132,936 adults. Of these, 55%, 78% and 66%, respectively, were female and 0.7% of YA, 22.3% of OA and 8.3% of adults were pregnant at ART initiation. Cumulative incidence of LTFU at five years was 26.6% (24.6 to 28.6) among YA, 44.1% (41.8 to 46.3) among OA and 29.3% (29.1 to 29.6) among adults. Overall, compared to adults, the adjusted hazard ratio, aHR, (95% CI) of LTFU for OA was 1.54 (1.41 to 1.68) and 0.77 (0.69 to 0.86) for YA. Compared to males, pregnant females had higher hazard of LTFU, aHR 1.20 (1.14 to 1.27), and nonpregnant women had lower hazard aHR 0.90 (0.88 to 0.93). LTFU hazard among the OA was primarily driven by both pregnant and nonpregnant females, aHR 2.42 (1.98 to 2.95) and 1.51 (1.27 to 1.80), respectively, compared to men. The LTFU hazard ratio varied by IeDEA program. Site‐level factors associated with overall lower LTFU hazard included receiving care in tertiary versus primary‐care clinics aHR 0.61 (0.56 to 0.67), integrated adult and adolescent services and food ration provision aHR 0.93 (0.89 to 0.97) versus nonintegrated clinics with food ration provision, having patient support groups aHR 0.77 (0.66 to 0.90) and group adherence counselling aHR 0.61 (0.57 to 0.67).

Conclusions

Older adolescents experienced higher risk of LTFU compared to YA and adults. Interventions to prevent LTFU among older adolescents are critically needed, particularly for female and/or pregnant adolescents.

     

A comparison of death recording by health centres and civil registration in South Africans receiving antiretroviral treatment

Introduction

There is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART).

Methods

Completeness of death recording was estimated using a capture–recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil identity document (ID) numbers and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes.

Results

After exclusions, 91,548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3–94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2–35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004–2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50 km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults).

Conclusions

South Africa''s civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously documented improvements in ART mortality over time may be biased if based only on data from patient records.     

Concurrent partnerships in Cape Town,South Africa: race and sex differences in prevalence and duration of overlap

Introduction

Concurrent partnerships (CPs) have been suggested as a risk factor for transmitting HIV, but their impact on the epidemic depends upon how prevalent they are in populations, the average number of CPs an individual has and the length of time they overlap. However, estimates of prevalence of CPs in Southern Africa vary widely, and the duration of overlap in these relationships is poorly documented. We aim to characterize concurrency in a more accurate and complete manner, using data from three disadvantaged communities of Cape Town, South Africa.

Methods

We conducted a sexual behaviour survey (n=878) from June 2011 to February 2012 in Cape Town, using Audio Computer-Assisted Self-Interviewing to collect sexual relationship histories on partners in the past year. Using the beginning and end dates for the partnerships, we calculated the point prevalence, the cumulative prevalence and the incidence rate of CPs, as well as the duration of overlap for relationships begun in the previous year. Linear and binomial regression models were used to quantify race (black vs. coloured) and sex differences in the duration of overlap and relative risk of having CPs in the past year.

Results

The overall point prevalence of CPs six months before the survey was 8.4%: 13.4% for black men, 1.9% for coloured men, 7.8% black women and 5.6% for coloured women. The median duration of overlap in CPs was 7.5 weeks. Women had less risk of CPs in the previous year than men (RR 0.43; 95% CI: 0.32–0.57) and black participants were more at risk than coloured participants (RR 1.86; 95% CI: 1.17–2.97).

Conclusions

Our results indicate that in this population the prevalence of CPs is relatively high and is characterized by overlaps of long duration, implying there may be opportunities for HIV to be transmitted to concurrent partners.     

Changes in second‐line regimen durability and continuity of care in relation to national ART guideline changes in South Africa

Introduction : Little is known about the impact of antiretroviral therapy (ART) guideline changes on the durability of second‐line ART and continuity of care. This study examines predictors of early drug substitutions and treatment interruptions using a cohort analysis of HIV positive adults switched to second‐line ART between January 2004 and September 2013 in Johannesburg, South Africa. Methods : The main outcomes were having a drug substitution or treatment interruption in the first 24 months on second‐line ART. Kaplan Meiers analyses and Cox proportional hazards regression were used to identify predictors of drug substitutions and treatment interruptions. Results : Of 3028 patients on second‐line ART, 353 (11.7%) had a drug substitution (8.6 per 100PY, 95% CI: 7.8–9.6) and 260 (8.6%) had a treatment interruption (6.3 per 100PY, 95% CI: 5.6–7.1). While treatment interruptions decreased from 32.5 per 100PY for the 2004 cohort to 2.3 per 100PY for the 2013 cohort, the rates of drug substitutions steadily increased, peaking at an incidence of 26.7 per 100PY for the 2009 cohort and then decreased to 4.2 per 100PY in the 2011 cohort. Compared to the 2004 to 2008 cohorts, the hazard of early drug substitutions was highest among patients switched to AZT + ddI + LPVr in 2009 to 2010 (aHR 5.1, 95% CI: 3.4–7.1) but remained low over time among patients switched to TDF + 3TC/FTC + LPVr or AZT/ABC + 3TC + LPVr. The main common predictor of both treatment interruption and drug substitution was drug toxicity. Conclusions : Our results show a rapid transition between 2004 and 2010 ART guidelines and concurrent improvements in continuity of care among second‐line ART patients. Drug toxicity reporting and monitoring systems need improvements to inform timely regimen changes and ensure that patients remain in care. However, reasons for drug substitutions should be closely monitored to ensure that patients do not run out of treatment options in the future.     

Barriers and facilitators to linkage to ART in primary care: a qualitative study of patients and providers in Blantyre,Malawi

Introduction

Linkage from HIV testing and counselling (HTC) to initiation of antiretroviral therapy (ART) is suboptimal in many national programmes in sub-Saharan Africa, leading to delayed initiation of ART and increased risk of death. Reasons for failure of linkage are poorly understood.

Methods

Semi-structured qualitative interviews were undertaken with health providers and HIV-positive primary care patients as part of a prospective cohort study at primary health centres in Blantyre, Malawi. Patients successful and unsuccessful in linking to ART were included.

Results

Progression through the HIV care pathway was strongly influenced by socio-cultural norms, particularly around the perceived need to regain respect lost during a period of visibly declining health. Capacity to call upon the support of networks of families, friends and employers was a key determinant of successful progression. Over-busy clinics, non-functioning laboratories and unsuitable tools used for ART eligibility assessment (WHO clinical staging system and centralized CD4 count measurement) were important health systems determinants of drop-out.

Conclusions

Key interventions that could rapidly improve linkage include guarantee of same-day, same-clinic ART eligibility assessments; utilization of the support offered by peer-groups and community health workers; and integration of HTC and ART programmes.     

Incidence of active tuberculosis among people living with HIV receiving long‐term antiretroviral therapy in high TB/HIV burden settings in Thailand: implication for tuberculosis preventive therapy

IntroductionAmong high tuberculosis (TB) and HIV burden countries in Asia, tuberculosis preventive therapy (TPT) in people living with HIV (PLWH) has been underutilized despite its proven benefits independent of antiretroviral therapy (ART). Therefore, we determined the incidence of active TB and mortality among 9179 adult PLWH who attended and received ART from 15 tertiary care hospitals across Thailand.MethodsA retrospective study was conducted in 2018 using follow‐up data from 1999 to 2018. The primary endpoint was incident TB disease after ART initiation. Factors associated with TB incidence were analysed using competing risk regression. The Kaplan–Meier method was used to estimate mortality after ART initiation.ResultsDuring a median of 5.1 years of ART (IQR 2.2–9.5 years), 442 (4.8%) PLWH developed TB (TB/HIV), giving an overall incidence of 750 (95% CI 683–823) per 100,000 persons‐year of follow up (PYFU). In multivariate analysis, lower CD4 at ART initiation (≤100 cells/mm³, adjusted sub‐distribution hazard ratio [aSHR]: 2.08, 95% CI, 1.47–2.92; 101–200 cells/mm³, aSHR: 2.21, 95% CI, 1.54–3.16; 201–350 cells/mm³, aSHR: 1.59, 95% CI, 1.11–2.28 vs. >350 cells/mm³), male sex (aSHR: 1.40, 95% CI, 1.11–1.78), lower body weight (<50 kg, aSHR: 1.52, 95% CI, 1.17–1.95) and prior TB event (aSHR: 3.50, 95% CI, 2.72–4.52) were associated with TB incidence. PLWH with HIV RNA ≥50 copies/ml had 5–9 times higher risk of active TB disease higher than those with HIV RNA <50 copies/ml at the same CD4 level. The risk for developing TB was remarkably high during the initial period of ART (175,511 per 100,000 PYFU at<3 months) and was comparable to the general population after 10 years of ART (151 per 100,000 PYFU). TB/HIV had higher mortality (10% vs. 5%) and poorer HIV treatment outcomes: HIV RNA <50 copies/ml (63.8% vs. 82.8%), CD4 cells count (317 vs. 508 cells/mm³) at the most recent visit.ConclusionsIn this high TB burden country, TB incidence was remarkably high during the first few years after ART initiation and thereafter decreased significantly. Rapid ART initiation and appropriate TPT can be potential key interventions to tackle the TB epidemic and reduce mortality among PLWH in TB/HIV high burden settings.     

Coital frequency and condom use in monogamous and concurrent sexual relationships in Cape Town,South Africa

Introduction

A decreased frequency of unprotected sex during episodes of concurrent relationships may dramatically reduce the role of concurrency in accelerating the spread of HIV. Such a decrease could be the result of coital dilution – the reduction in per-partner coital frequency from additional partners – and/or increased condom use during concurrency. To study the effect of concurrency on the frequency of unprotected sex, we examined sexual behaviour data from three communities with high HIV prevalence around Cape Town, South Africa.

Methods

We conducted a cross-sectional survey from June 2011 to February 2012 using audio computer-assisted self-interviewing to reconstruct one-year sexual histories, with a focus on coital frequency and condom use. Participants were randomly sampled from a previous TB and HIV prevalence survey. Mixed effects logistic and Poisson regression models were fitted to data from 527 sexually active adults reporting on 1210 relationship episodes to evaluate the effect of concurrency status on consistent condom use and coital frequency.

Results

The median of the per-partner weekly average coital frequency was 2 (IQR: 1–3), and consistent condom use was reported for 36% of the relationship episodes. Neither per-partner coital frequency nor consistent condom use changed significantly during episodes of concurrency (aIRR=1.05; 95% confidence interval (CI): 0.99–1.24 and aOR=1.01; 95% CI: 0.38–2.68, respectively). Being male, coloured, having a tertiary education, and having a relationship between 2 weeks and 9 months were associated with higher coital frequencies. Being coloured, and having a relationship lasting for more than 9 months, was associated with inconsistent condom use.

Conclusions

We found no evidence for coital dilution or for increased condom use during concurrent relationship episodes in three communities around Cape Town with high HIV prevalence. Given the low levels of self-reported consistent condom use, our findings suggest that if the frequency of unprotected sex with each of the sexual partners is sustained during concurrent relationships, HIV-positive individuals with concurrent partners may disproportionately contribute to onward HIV transmission.     

Impact on ART initiation of point-of-care CD4 testing at HIV diagnosis among HIV-positive youth in Khayelitsha,South Africa

Introduction

Despite the rapid expansion of antiretroviral therapy (ART) programmes in developing countries, pre-treatment losses from care remain a challenge to improving access to treatment. Youth and adolescents have been identified as a particularly vulnerable group, at greater risk of loss from both pre-ART and ART care. Point-of-care (POC) CD4 testing has shown promising results in improving linkage to ART care. In Khayelitsha township, South Africa, POC CD4 testing was implemented at a clinic designated for youth aged 12–25 years. We assessed whether there was an associated reduction in attrition between HIV testing, assessment for eligibility and ART initiation.

Methods

A before-and-after observational study was conducted using routinely collected data. These were collected on patients from May 2010 to April 2011 (Group A) when baseline CD4 count testing was performed in a laboratory and results were returned to the clinic within two weeks. Same-day POC CD4 testing was implemented in June 2011, and data were collected on patients from August 2011 to July 2012 (Group B).

Results

A total of 272 and 304 youth tested HIV-positive in Group A and Group B, respectively. Group B patients were twice as likely to have their ART eligibility assessed compared to Group A patients: 275 (90%) vs. 183 (67%) [relative risk (RR)=2.4, 95% CI: 1.8–3.4, p<0.0001]. More patients in World Health Organization (WHO) Stage 1 disease (85% vs. 69%), with CD4 counts≥350 cells/µL (58% vs. 35%) and more males (13% vs. 7%) were detected in Group B. The proportion of eligible patients who initiated ART was 50% and 44% (p=0.6) in Groups B and A, respectively; and 50% and 43% (p=0.5) when restricted to patients with baseline CD4 count≤250 cells/µL. Time between HIV-testing and ART initiation was reduced from 36 to 28 days (p=0.6).

Discussion

POC CD4 testing significantly improved assessment for ART eligibility. The improvement in the proportion initiating ART and the reduction in time to initiation was not significant due to sample size limitations.

Conclusions

POC CD4 testing reduced attrition between HIV-testing and assessment of ART eligibility. Strategies to improve uptake of ART are needed, possibly by improving patient support for HIV-positive youth immediately after diagnosis.