Motivating people living with HIV to initiate antiretroviral treatment outside national guidelines in three clinics in the HPTN 071 (PopART) trial, South Africa.

Background: The HPTN 071 (PopART) trial implemented universal test and treat (UTT) in three clinics in the Western Cape, South Africa at a time when antiretroviral treatment (ART) was only offered by CD4 threshold and World Health Organization clinical staging. This required a concomitant shift in the way health workers communicated ART initiation messages. We provide insight into front-line ART initiation communication pre-national policy shift.Method: The design of this study was exploratory with a case descriptive analysis of ART initiation in three clinics. To characterise their demographic profiles, we reviewed 134 randomly selected patient clinical folders of people who initiated ART at CD4 counts greater than the recommended standard. Further, we conducted 12 key informant interviews with health workers at these facilities and thematically analysed health workers' responses.Results: The median age of patients initiating ART regardless of CD4 count (above the threshold level) was 33 years and most were women (73.9%), married (76.1%), and unemployed (48.5%). The median CD4 count of patients initiating outside guidelines was 566.5 cells/µl. Contrary to expectations, key informants indicated no radical shift in messaging to explain ART initiation regardless of CD4 count. Rather, they encouraged people living with HIV (PLHIV) to initiate ART while they still "feel well". The reduced risk of onward HIV transmission did not factor significantly in how health workers motivated clients.Conclusion: Motivating PLHIV to initiate ART regardless of CD4 count in high burden settings is possible. However, there are still opportunities to improve messaging about immediate ART initiation or at high CD4 counts for the prevention of onward transmission.

The Continuing Burden of Advanced HIV Disease Over 10 Years of Increasing Antiretroviral Therapy Coverage in South Africa.

Background: Antiretroviral treatment (ART) has been massively scaled up to decrease human immunodeficiency virus (HIV)-related morbidity, mortality, and HIV transmission. However, despite documented increases in ART coverage, morbidity and mortality have remained substantial. This study describes trends in the numbers and characteristics of patients with very advanced HIV disease in the Western Cape, South Africa. Methods: Annual cross-sectional snapshots of CD4 distributions were described over 10 years, derived from a province-wide cohort of all HIV patients receiving CD4 cell count testing in the public sector. Patients with a first CD4 count <50 cells/µL in each year were characterized with respect to prior CD4 and viral load testing, ART access, and retention in ART care. Results: Patients attending HIV care for the first time initially constituted the largest group of those with CD4 count <50 cells/µL, dropping proportionally over the decade from 60.9% to 26.7%. By contrast, the proportion who were ART experienced increased from 14.3% to 56.7%. In patients with CD4 counts <50 cells/µL in 2016, 51.8% were ART experienced, of whom 76% could be confirmed to be off ART or had recent viremia. More than half who were ART experienced with a CD4 count <50 cells/µL in 2016 were men, compared to approximately one-third of all patients on ART in the same year. Conclusions: Ongoing HIV-associated morbidity now results largely from treatment-experienced patients not being in continuous care or not being fully virologically suppressed. Innovative interventions to retain ART patients in effective care are an essential priority for the ongoing HIV response.

Strategies for supporting the implementation of a task-shared psychological intervention in South Africa's chronic disease services: qualitative insights from health managers' experiences of project MIND.

BACKGROUND: Although evidence indicates that task-shared psychological interventions can reduce mental health treatment gaps in resource-constrained settings, systemic barriers have limited their widespread implementation. Evidence on how to sustain and scale such approaches is scant. This study responds to this gap by examining the experiences of South African health managers involved in the implementation of a task-shared counselling service for Project MIND. OBJECTIVES: To qualitatively describe managers' experiences of implementing the MIND programme and their insights into potential strategies for supporting sustained implementation. METHODS: Two focus group discussions (FGDs) and eight in-depth interviews (IDIs) were conducted with managers of urban and rural primary care facilities in the Western Cape province. All managers were female and 30-50 years old. FGDs and IDIs used an identical semi-structured topic guide to explore the experiences of the MIND programme and perceived barriers to sustained implementation. Normalisation process theory (NPT) guided the thematic analysis. RESULTS: Four themes emerged that mapped onto the NPT constructs. First, managers noted that their relational work with staff to promote support for the intervention and reduce resistance was key to facilitating implementation. Second, managers emphasised the need for staff reorientation and upskilling to foster openness to mental health practice and for adequate time for quality counselling. Third, managers underscored the importance of strengthening linkages between the health and social service sectors to facilitate delivery of comprehensive mental health services. Finally, managers recommended ongoing monitoring of the service and communication about its impacts as strategies for supporting integration into routine practice. CONCLUSIONS: Findings contribute to the emerging literature on strategies to support implementation of task-shared interventions in low- and middle-income countries. The findings highlight the leadership role of managers in identifying and actioning these strategies. Investing in managers' capacity to support implementation of psychological interventions is critical for scale-up of these mental health innovations.

Implementing 'universal' access to antiretroviral treatment in South Africa: a scoping review on research priorities.

'Universal' access to antiretroviral treatment (ART) has become the global standard for treating people living with HIV and achieving epidemic control; yet, findings from numerous 'test and treat' trials and implementation studies in sub-Saharan Africa suggest that bringing 'universal' access to ART to scale is more complex than anticipated. Using South Africa as a case example, we describe the research priorities and foci in the literature on expanded ART access. To do so, we adapted Arksey and O'Malley's six-stage scoping review framework to describe the peer-reviewed literature and opinion pieces on expanding access to ART in South Africa between 2000 and 2017. Data collection included systematic searches of two databases and hand-searching of a sub-sample of reference lists. We used an adapted socio-ecological thematic framework to categorize data according to where it located the challenges and opportunities of expanded ART eligibility: individual/client, health worker-client relationship, clinic/community context, health systems infrastructure and/or policy context. We included 194 research articles and 23 opinion pieces, of 1512 identified, addressing expanded ART access in South Africa. The peer-reviewed literature focused on the individual and health systems infrastructure; opinion pieces focused on changing roles of individuals, communities and health services implementers. We contextualized our findings through a consultative process with a group of researchers, HIV clinicians and programme managers to consider critical knowledge gaps. Unlike the published literature, the consultative process offered particular insights into the importance of researching and intervening in the relational aspects of HIV service delivery as South Africa's HIV programme expands. An overwhelming focus on individual and health systems infrastructure factors in the published literature on expanded ART access in South Africa may skew understanding of HIV programme shortfalls away from the relational aspects of HIV services delivery and delay progress with finding ways to leverage non-medical modalities for achieving HIV epidemic control.

Young South African Women on Antiretroviral Therapy Perceptions of a Psychological Counselling Program to Reduce Heavy Drinking and Depression.

Young women in South Africa remain most at risk for HIV infection. Several factors contribute to the high incidence rate in this population, including hazardous drinking and depression. Addressing common mental disorders (CMDs) such as depression and alcohol use disorders is key to effective HIV treatment. We explored the experiences and perceptions of young South African women on antiretroviral therapy (ART) of a lay health worker (LHW)-delivered psychosocial intervention based on motivational interviewing (MI) and problem-solving therapy (PST) to reduce heavy drinking and depression. We conducted 27 in-depth interviews with young women (aged 18-35) recruited from 16 primary care clinics in the Western Cape province of South Africa. Discussion topics included young women's life experiences leading to their enrollment in the program, their perceptions of the counselling sessions and the quality of their interaction with the counsellor. Qualitative data were analyzed using a framework approach. The findings highlighted the impact adverse life experiences and stressful life circumstances have on young women's use of alcohol and symptoms of depression and the effect this has on ART adherence. The findings suggest that women found the intervention components that helped them develop strategies for coping with their past experiences, managing current life stressors, and regulating negative thoughts and emotions most beneficial. Taken together, these findings confirm the acceptability of LHW-delivered MI-PST counselling for this population, but suggest that the relevance of the MI-PST intervention for this highly vulnerable population could be further enhanced by including a focus on psychological trauma.

'Doing more with less': a qualitative investigation of perceptions of South African health service managers on implementation of health innovations.

Building resilience in health systems is an imperative for low- and middle- income countries. Health service managers' ability to implement health innovations may be a key aspect of resilience in primary healthcare facilities, promoting adaptability and functionality. This study investigated health service managers' perceptions and experiences of adopting health innovations. We aimed to identify perceptions of constraints to adoption and emergent behaviours in response to these constraints. A convenience sample of 34 facility, clinical service and sub-district level managers was invited to participate. Six did not respond and were not contactable. In-depth individual interviews in a private space at participants' place of work were conducted with 28 participants. Interviews were audio recorded and transcribed verbatim. NVivo 11 was used to store data and facilitate framework analysis. Study participants described constraints to innovation adoption including: staff lack of understanding of potential benefits; staff personalities, attitudes and behaviours which lead to resistance to change; high workload related to resource constraints and frequent policy changes inducing resistance to change; and suboptimal communication through health system structures. Managers reported employing various strategies to mitigate these constraints. These comprised (1) technical skills including participatory management skills, communication skills, community engagement skills and programme monitoring and evaluation skills, and (2) non-technical skills including role modelling positive attitudes, understanding staff personalities, influencing perceptions of innovations, influencing organizational climate and building trusting relationships. Managers have a vital role in the embedding of service innovations into routine practice. We present a framework of technical and non-technical skills that managers need to facilitate the adoption of health innovations. Future efforts to build managers' capacity to implement health innovations should target these competencies.

Retention in care and factors critical for effectively implementing antiretroviral adherence clubs in a rural district in South Africa.

INTRODUCTION: Differentiated models of care that include referral of antiretroviral treatment (ART) clients to adherence clubs are an important strategy to help clinics manage increased number of clients living with HIV in resource-constrained settings. This study reported on (i) clinical outcomes among ART clients attending community-based adherence clubs and (ii) experiences of adherence clubs and perceptions of factors key to successful adherence club implementation among clients and healthcare workers. METHODS: A retrospective cohort analysis of routine data and a descriptive analysis of data collected through self-administered surveys completed by clients and healthcare workers were completed. Clients starting ART at the study clinic, between January 2014 and December 2015, were included in the cohort analysis and followed up until December 2016. The survey data were collected from August to September 2017. The primary outcome for the cohort analysis was a comparison of loss to follow-up (LTFU) between clients staying in clinic care and those referred to adherence clubs. Survey data reported on client experiences of and healthcare worker perceptions of adherence club care. RESULTS: Cohort analysis reported on 465 participants, median baseline CD4 count 374 (IQR: 234 to 532) cells/µl and median follow-up time 20.7 (IQR 14.1 to 27.7) months. Overall, 202 (43.4%) participants were referred to an adherence club. LTFU was lower in those attending an adherence club (aHR =0.25, 95% CI: 0.11 to 0.56). This finding was confirmed on analysis restricted to those eligible for adherence club referral (aHR =0.28, 95% CI: 0.12 to 0.65). Factors highlighted as associated with successful adherence club implementation included: (i) referral of stable clients to the club, (ii) an ideal club size of ≥20 members, (iii) club services led by a counsellor (iv) using churches or community halls as venues (v) effective communication between all parties, and (vi) timely delivery of prepacked medication. CONCLUSIONS: This study showed good clinical outcomes, positive patient experiences and healthcare worker perceptions of the adherence club model. Factors associated with successful adherence club implementation, highlighted in this study, can be used to guide implementers in the scale-up of adherence club services across varied high-burden settings.

Attrition when providing antiretroviral treatment at CD4 counts >500cells/µL at three government clinics included in the HPTN 071 (PopART) trial in South Africa.

INTRODUCTION: WHO recommends antiretroviral treatment (ART) for all HIV-positive individuals. This study evaluated the association between baseline CD4 count and attrition in a cohort of HIV positive adults initiating ART at three department of health (DOH) clinics routinely providing ART at baseline CD4 counts >500cells/µL for the HPTN 071 (PopART) trial. METHODS: All clients attending the DOH clinics were managed according to standard care guidelines with the exception that those starting ART outside of pertinent local guidelines signed research informed consent. DOH data on all HIV-positive adult clients recorded as having initiated ART between January 2014 and November 2015 at the three study clinics was analysed. Attrition, included clients lost to follow up or died, and was defined as 'being three or more months late for an antiretroviral pharmacy pick-up appointment'. All clients were followed until attrition, transfer out or end May 2016. RESULTS: A total of 2423 clients with a median baseline CD4 count of 328 cells/µL (IQR 195-468) were included of whom 631 (26.0%) experienced attrition and 140 (5.8%) were TFO. Attrition was highest during the first six months of ART (IR 38.3/100 PY; 95% CI 34.8-42.1). Higher attrition was found amongst those with baseline CD4 counts > 500 cells/µL compared to those with baseline CD4 counts of 0-500 cells/µL (aHR 1.26, 95%CI 1.05 to 1.52) This finding was confirmed on subset analyses when restricted to individuals non-pregnant at baseline and when restricted to individuals with follow up of > 12months. CONCLUSIONS: Attrition in this study was high, particularly during the first six months of treatment. Attrition was highest amongst clients starting ART at baseline CD4 counts > 500 cells/µL. Strategies to improve retention amongst ART clients, particularly those starting ART at baseline CD4 counts >500cells/µL, need strengthening. Improved monitoring of clients moving in and out of ART care and between clinics will assist in better understanding attrition and ART coverage in high burden countries.

Incidence of Tuberculosis Among HIV-Positive Individuals Initiating Antiretroviral Treatment at Higher CD4 Counts in the HPTN 071 (PopART) Trial in South Africa.

INTRODUCTION: Antiretroviral treatment (ART) guidelines recommend life-long ART for all HIV-positive individuals. This study evaluated tuberculosis (TB) incidence on ART in a cohort of HIV-positive individuals starting ART regardless of CD4 count in a programmatic setting at 3 clinics included in the HPTN 071 (PopART) trial in South Africa. METHODS: A retrospective cohort analysis of HIV-positive individuals aged ≥18 years starting ART, between January 2014 and November 2015, was conducted. Follow-up was continued until 30 May 2016 or censored on the date of (1) incident TB, (2) loss to follow-up from HIV care or death, or (3) elective transfer out; whichever occurred first. RESULTS: The study included 2423 individuals. Median baseline CD4 count was 328 cells/µL (interquartile range 195-468); TB incidence rate was 4.41/100 person-years (95% confidence interval [CI]: 3.62 to 5.39). The adjusted hazard ratio of incident TB was 0.27 (95% CI: 0.12 to 0.62) when comparing individuals with baseline CD4 >500 and ≤500 cells/µL. Among individuals with baseline CD4 count >500 cells/µL, there were no incident TB cases in the first 3 months of follow-up. Adjusted hazard of incident TB was also higher among men (adjusted hazard ratio 2.16; 95% CI: 1.41 to 3.30). CONCLUSIONS: TB incidence after ART initiation was significantly lower among individuals starting ART at CD4 counts above 500 cells/µL. Scale-up of ART, regardless of CD4 count, has the potential to significantly reduce TB incidence among HIV-positive individuals. However, this needs to be combined with strengthening of other TB prevention strategies that target both HIV-positive and HIV-negative individuals.

Safety and pharmacodynamics of dalazatide, a Kv1.3 channel inhibitor, in the treatment of plaque psoriasis: A randomized phase 1b trial.

BACKGROUND: Dalazatide is a specific inhibitor of the Kv1.3 potassium channel. The expression and function of Kv1.3 channels are required for the function of chronically activated memory T cells, which have been shown to be key mediators of autoimmune diseases, including psoriasis. OBJECTIVE: The primary objective was to evaluate the safety of repeat doses of dalazatide in adult patients with mild-to-moderate plaque psoriasis. Secondary objectives were to evaluate clinical proof of concept and the effects of dalazatide on mediators of inflammation in the blood and on chronically activated memory T cell populations. METHODS: Patients (n = 24) were randomized 5:5:2 to receive dalazatide at 30 mcg/dose, 60 mcg/dose, or placebo twice weekly by subcutaneous injection (9 doses total). Safety was assessed on the basis of physical and neurological examination and laboratory testing. Clinical assessments included body-surface area affected, Psoriasis Area and Severity Index (PASI), and investigator and patient questionnaires. RESULTS: The most common adverse events were temporary mild (Grade 1) hypoesthesia (n = 20; 75% placebo, 85% dalazatide) and paresthesia (n = 15; 25% placebo, 70% dalazatide) involving the hands, feet, or perioral area. Nine of 10 patients in the 60 mcg/dose group had a reduction in their PASI score between baseline and Day 32, and the mean reduction in PASI score was significant in this group (P < 0.01). Dalazatide treatment reduced the plasma levels of multiple inflammation markers and reduced the expression of T cell activation markers on peripheral blood memory T cells. LIMITATIONS: The study was small and drug treatment was for a short duration (4 weeks). CONCLUSION: This study indicates that dalazatide is generally well tolerated and can improve psoriatic skin lesions by modulating T cell surface and activation marker expression and inhibiting mediators of inflammation in the blood. Larger studies of longer duration are warranted.