Implementation and outcomes of dolutegravir-based first-line antiretroviral therapy for people with HIV in South Africa: a retrospective cohort study.

BACKGROUND: There are few data assessing the uptake of first-line dolutegravir among men and women living with HIV in low-income and middle-income countries, and subsequent clinical outcomes in non-trial settings. We aimed to determine dolutegravir uptake in women, and the effect of dolutegravir on clinical outcomes in routine care in South Africa. METHODS: In this cohort study, we analysed deidentified data from adults receiving first-line antiretroviral therapy (ART) at 59 South African clinics from Dec 1, 2019, to Feb 28, 2022, using two distinct cohorts. In the initiator cohort, we used Poisson regression models to assess the outcome of initiation with dolutegravir-based ART by gender, and associations between dolutegravir use and the outcomes of 12-month retention in care and viral suppression at less than 50 copies per mL. In the transition cohort, comprising adults who received non-dolutegravir-based first-line ART in December, 2019, we used Cox proportional hazards models to assess the outcome of transition to first-line dolutegravir by gender. We then used time-dependent propensity score matching to compare the outcomes of subsequent 12-month retention in care and viral suppression between people who transitioned to dolutegravir and those who had not yet transitioned at the same timepoint. In both the initiation and transition cohort, the primary viral load analysis was an intention-to-treat analysis, with a secondary as-treated analysis that excluded people who changed their ART regimen after baseline. FINDINGS: In the initiator cohort, between Dec 1, 2019, and Feb 28, 2022, 45 392 people were initiated on ART. 23 945 (52·8%) of 45 392 were non-pregnant women, 4780 (10·5%) were pregnant women, and 16 667 (36·7%) were men. The median participant age was 31·0 years (IQR 26·0-38·0) and 2401 (5·3%) were receiving tuberculosis treatment at time of ART initiation. 31 264 (68·9%) of 45 392 people were initiated on dolutegravir, 14 102 (31·1%) on efavirenz, and 26 (0·1%) on nevirapine. In a univariable Poisson regression model, pregnant women (risk ratio [RR] 0·57, 95% CI 0·49 to 0·66; risk difference -35·4%, 95% CI -42·3 to -28·5) and non-pregnant women (RR 0·78, 0·74 to 0·82; risk difference -18·4%, -21·6 to -15·2) were less likely to be initiated on dolutegravir than were men. In Poisson models adjusted for age, gender (including pregnancy), time, tuberculosis status, and initiation CD4 count, people initiated on dolutegravir were more likely to be retained in care at 12 months (adjusted RR 1·09, 95% CI 1·04 to 1·14; adjusted risk difference 5·2%, 2·2 to 8·4) and virally suppressed (adjusted RR 1·04, 95% CI 1·01 to 1·06; adjusted risk difference 3·1%, 1·2 to 5·1) compared with those initiated on non-dolutegravir-based regimens. For the transition cohort, on Dec 1, 2019, 180 956 people were receiving non-dolutegravir-based first-line ART at the study clinics, of whom 124 168 (68·6%) were women. The median age was 38 years (IQR 32-45), and the median time on ART was 3·9 years (2·0-6·4) years, with most people receiving efavirenz (178 624 [98·7%] people) and tenofovir (178 148 [98·4%]). By Feb 28, 2022, 121 174 (67·0%) of 180 956 people had transitioned to first-line dolutegravir at a median of 283 days (IQR 203-526). In a univariable Cox regression model the hazard of being transitioned to dolutegravir was lower in women than in men (hazard ratio 0·56, 95% CI 0·56 to 0·57). Among 92 318 propensity score matched people, the likelihood of retention in care was higher among the dolutegravir group compared with matched controls (adjusted RR 1·03, 95% CI 1·02 to 1·03; risk difference 2·5%, 95% CI 2·1 to 2·9). In the dolutegravir group, 33 423 (90·5%) of 36 920 people were suppressed at less than 50 copies per mL compared with 31 648 (89·7%) of 35 299 matched controls (adjusted RR 1·01, 95% CI 1·00 to 1·02; risk difference 0·8%, 95% CI 0·3 to 1·4). INTERPRETATION: Women were less likely to receive dolutegravir than men. As dolutegravir was associated with improved outcomes, roll-out should continue, with a particular emphasis on inclusion of women. FUNDING: Wellcome Trust, Africa Oxford Initiative, International Association of Providers of AIDS Care, and Bill & Melinda Gates Foundation. TRANSLATION: For the isiZulu translation of the abstract see Supplementary Materials section.

Evaluation of the effectiveness of a quality improvement intervention to support integration of maternal, child and HIV care in primary health care facilities in South Africa.

BACKGROUND: Despite policies and guidelines recommending integration of health services in South Africa, provision of maternal and child health services remains fragmented. This study evaluated a rapid, scaleable, quality improvement (QI) intervention to improve integration of maternal and child health and HIV services at a primary health level, in KwaZulu-Natal, South Africa. METHODS: A three-month intervention comprised of six QI mentoring visits, learning sessions with clinic staff to share learnings, and a self-administered checklist aimed to assist health workers monitor and implement an integrated package of health services for mothers and children. The study evaluated 27 clinics in four sub-districts using a stepped-wedge design. Each sub-district received the intervention sequentially in a randomly selected order. Five waves of data collection were conducted in all participating clinics between December 2016-February 2017. A multi-level, mixed effects logistic regression was used to account for random cluster fixed time and group effects using Stata V13.1. RESULTS: Improvements in some growth monitoring indicators were achieved in intervention clinics compared to control clinics, including measuring the length of the baby (77% vs 63%; p = 0.001) and health workers asking mothers about the child's feeding (74% vs 67%; p = 0.003), but the proportion of mothers who received feeding advice remained unchanged (38% vs 35%; p = 0.48). Significantly more mothers in the intervention group were asked about their baby's health (44% vs 36%; p = 0.001), and completeness of record keeping improved (40% vs 26%; I = < 0.0001). Discussions with the mother about some maternal health services improved: significantly more mothers in the intervention group were asked about HIV (26.5% vs 19.5%; p = 0.009) and family planning (33.5% vs 19.5%; p <  0.001), but this did not result in additional services being provided to mothers at the clinic visit. CONCLUSION: This robust evaluation shows significant improvements in coverage of some services, but the QI intervention was unable to achieve the substantial changes required to provide a comprehensive package of services to all mothers and children. We suggest the QI process be adapted to complex under-resourced health systems, building on the strengths of this approach, to provide workable health systems strengthening solutions for scalable implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04278612. Date of Registration: February 19, 2020. Retrospectively registered.

Trust of community health workers influences the acceptance of community-based maternal and child health services.

BACKGROUND: Community health workers (CHWs) are a component of the health system in many countries, providing effective community-based services to mothers and infants. However, implementation of CHW programmes at scale has been challenging in many settings. AIM: To explore the acceptability of CHWs conducting household visits to mothers and infants during pregnancy and after delivery, from the perspective of community members, professional nurses and CHWs themselves. SETTING: Primary health care clinics in five rural districts in KwaZulu-Natal, South Africa. METHODS: A qualitative exploratory study was conducted where participants were purposively selected to participate in 19 focus group discussions based on their experience with CHWs or child rearing. RESULTS: Poor confidentiality and trust emerged as key barriers to CHW acceptability in delivering maternal and child health services in the home. Most community members felt that CHWs could not be trusted because of their lack of professionalism and inability to maintain confidentiality. Familiarity and the complex relationships between household members and CHWs caused difficulties in developing and maintaining a relationship of trust, particularly in high HIV prevalence settings. Professional staff at the clinic were crucial in supporting the CHW's role; if they appeared to question the CHW's competency or trustworthiness, this seriously undermined CHW credibility in the eyes of the community. CONCLUSION: Understanding the complex contextual challenges faced by CHWs and community members can strengthen community-based interventions. CHWs require training, support and supervision to develop competencies navigating complex relationships within the community and the health system to provide effective care in communities.

Insights into health care seeking behaviour for children in communities in KwaZulu-Natal, South Africa.

BACKGROUND: South African infant and child mortality remains high, with many deaths occurring outside the formal health services. Delayed health care seeking represents a large proportion of these deaths. AIM: To generate knowledge about the role of, and influences on, caregivers with regard to decision-making about when and where to seek care for sick children. SETTING: Two communities in KwaZulu-Natal. METHODS: A qualitative, exploratory design employing participatory research techniques was used to undertake focus group discussions with community members. RESULTS: Health care seeking for a sick child was described as a complex process influenced by multiple carers using multiple providers. Decision-making about seeking health care for a sick child was not an individual effort, but was shared with others in the household and guided by how the symptoms were perceived, either a Western illness or African illness. A sick child could either be treated at home or be taken to a variety of places including clinics, private doctors, traditional healers, faith healers and hospitals. Traditional healers were associated with the treatment of illnesses perceived to be traditional. Few participants said that they would take their child back to the original health provider if the child remained ill, but would move from one provider to another until the child's health improved. CONCLUSION: The formal health system needs to ensure that sick children are identified and managed appropriately to reduce child deaths. Knowledge and understanding of health care seeking behaviour for sick children by carers is an important aspect. Interventions need to be designed with these contextual issues in mind.

A continuous quality improvement intervention to improve the effectiveness of community health workers providing care to mothers and children: a cluster randomised controlled trial in South Africa.

BACKGROUND: Community health workers (CHWs) play key roles in delivering health programmes in many countries worldwide. CHW programmes can improve coverage of maternal and child health services for the most disadvantaged and remote communities, leading to substantial benefits for mothers and children. However, there is limited evidence of effective mentoring and supervision approaches for CHWs. METHODS: This is a cluster randomised controlled trial to investigate the effectiveness of a continuous quality improvement (CQI) intervention amongst CHWs providing home-based education and support to pregnant women and mothers. Thirty CHW supervisors were randomly allocated to intervention (n = 15) and control (n = 15) arms. Four CHWs were randomly selected from those routinely supported by each supervisor (n = 60 per arm). In the intervention arm, these four CHWs and their supervisor formed a quality improvement team. Intervention CHWs received a 2-week training in WHO Community Case Management followed by CQI mentoring for 12 months (preceded by 3 months lead-in to establish QI processes). Baseline and follow-up surveys were conducted with mothers of infants <12 months old living in households served by participating CHWs. RESULTS: Interviews were conducted with 736 and 606 mothers at baseline and follow-up respectively; socio-demographic characteristics were similar in both study arms and at each time point. At follow-up, compared to mothers served by control CHWs, mothers served by intervention CHWs were more likely to have received a CHW visit during pregnancy (75.7 vs 29.0%, p < 0.0001) and the postnatal period (72.6 vs 30.3%, p < 0.0001). Intervention mothers had higher maternal and child health knowledge scores (49 vs 43%, p = 0.02) and reported higher exclusive breastfeeding rates to 6 weeks (76.7 vs 65.1%, p = 0.02). HIV-positive mothers served by intervention CHWs were more likely to have disclosed their HIV status to the CHW (78.7 vs 50.0%, p = 0.007). Uptake of facility-based interventions were not significantly different. CONCLUSIONS: Improved training and CQI-based mentoring of CHWs can improve quantity and quality of CHW-mother interactions at household level, leading to improvements in mothers' knowledge and infant feeding practices. TRIAL REGISTRATION: ClinicalTrials.Gov NCT01774136.

Fragmentation of maternal, child and HIV services: A missed opportunity to provide comprehensive care.

BACKGROUND: In South Africa, coverage of services for mothers and babies in the first year of life is suboptimal despite high immunisation coverage over the same time period. Integration of services could improve accessibility of services, uptake of interventions and retention in care. AIM: This study describes provision of services for mothers and babies aged under 1 year. SETTING: Primary healthcare clinics in one rural district in KwaZulu-Natal, South Africa. METHODS: All healthcare workers on duty and mothers exiting the clinic after attending well-child services were interviewed. Clinics were mapped to show the route through the clinic taken by mother-baby pairs receiving well-child services, where these services were provided and by whom. RESULTS: Twelve clinics were visited; 116 health workers and 211 mothers were interviewed. Most clinics did not provide comprehensive services for mothers and children. Challenges of structural layout and deployment of equipment led to fragmented services provided by several different health workers in different rooms. Well-child services were frequently provided in public areas of the clinic or with other mothers present. In some clinics mothers and babies did not routinely see a professional nurse. In all clinics HIV-positive mothers followed a different route. Enrolled nurses led the provision of well-child services but did not have skills and training to provide comprehensive care. CONCLUSIONS: Fragmentation of clinic services created barriers in accessing a comprehensive package of care resulting in missed opportunities to provide services. Greater integration of services alongside immunisation services is needed.

Reversing hard won victories in the name of human rights: a critique of the General Comment on Article 12 of the UN Convention on the Rights of Persons with Disabilities.

The UN Convention on the Rights of Persons with Disabilities (CRPD) is a major milestone in safeguarding the rights of persons with disabilities. However, the General Comment on Article 12 of the CRPD threatens to undermine critical rights for persons with mental disabilities, including the enjoyment of the highest attainable standard of health, access to justice, the right to liberty, and the right to life. Stigma and discrimination might also increase. Much hinges on the Committee on the Rights of Persons with Disabilities' view that all persons have legal capacity at all times irrespective of mental status, and hence involuntary admission and treatment, substitute decision-making, and diversion from the criminal justice system are deemed indefensible. The General Comment requires urgent consideration with the full participation of practitioners and a broad range of user and family groups.

HIV-infected adolescent mothers and their infants: low coverage of HIV services and high risk of HIV transmission in KwaZulu-Natal, South Africa.

OBJECTIVES: Rates of pregnancy and HIV infection are high among South African adolescents, yet little is known about rates of mother-to-child transmission of HIV (MTCT) in this group. We report a comparison of the characteristics of adolescent mothers and adult mothers, including HIV prevalence and MTCT rates. METHODS: We examined patterns of health service utilization during the antenatal and early postnatal period, HIV prevalence and MTCT amongst adolescent (<20-years-old) and adult (20 to 39-years-old) mothers with infants aged ≤16 weeks attending immunization clinics in six districts of KwaZulu-Natal between May 2008 and April 2009. FINDINGS: Interviews were conducted with 19,093 mothers aged between 12 and 39 years whose infants were aged ≤16 weeks. Most mothers had attended antenatal care four or more times during their last pregnancy (80.3%), and reported having an HIV test (98.2%). A greater proportion of HIV-infected adult mothers, compared to adolescent mothers, reported themselves as HIV-positive (41.2% vs. 15.9%, p<0.0001), reported having a CD4 count taken during their pregnancy (81.0% vs. 66.5%, p<0.0001), and having received the CD4 count result (84.4% vs. 75.7%, p<0.0001). Significantly fewer adolescent mothers received the recommended PMTCT regimen. HIV antibody was detected in 40.4% of 7,800 infants aged 4-8 weeks tested for HIV, indicating HIV exposure. This was higher among infants of adult mothers (47.4%) compared to adolescent mothers (17.9%, p<0.0001). The MTCT rate at 4-8 weeks of age was significantly higher amongst infants of adolescent mothers compared to adult mothers (35/325 [10.8%] vs. 185/2,800 [6.1%], OR 1.7, 95% CI 1.2-2.4). CONCLUSION: Despite high levels of antenatal clinic attendance among pregnant adolescents in KwaZulu-Natal, the MTCT risk is higher among infants of HIV-infected adolescent mothers compared to adult mothers. Access to adolescent-friendly family planning and PMTCT services should be prioritised for this vulnerable group.

Elimination of paediatric HIV in KwaZulu-Natal, South Africa: large-scale assessment of interventions for the prevention of mother-to-child transmission.

OBJECTIVE: To report the rates of mother-to-child transmission (MTCT) of the human immunodeficiency virus (HIV), and the coverage of interventions designed to prevent such transmission, in KwaZulu-Natal. METHODS: Mothers with infants aged ≤ 16 weeks and fathers or legal guardians with infants aged 4-8 weeks who, between May 2008 and April 2009, attended immunization clinics in six districts of KwaZulu-Natal were included. The mothers' uptake of interventions for the prevention of MTCT was explored. Blood samples from infants aged 4-8 weeks were tested for anti-HIV antibodies and, if antibody-positive, for HIV desoxyribonucleic acid (DNA). FINDINGS: Of the 19,494 mothers investigated, 89·9% reported having had an HIV test in their recent pregnancy. Of the 19,138 mothers who reported ever having had an HIV test, 34.4% reported that they had been found HIV-positive and, of these, 13.7% had started lifelong antiretroviral treatment and 67.2% had received zidovudine and nevirapine. Overall, 40.4% of the 7981 infants tested were found positive for anti-HIV antibodies, indicating HIV exposure. Just 7.1% of the infants checked for HIV DNA (equating to 2.8% of the infants tested for anti-HIV antibodies) were found positive. CONCLUSION: The low levels of MTCT observed among the infants indicate the rapid, successful implementation of interventions for the prevention of such transmission. Sampling at immunization clinics appears to offer a robust method of estimating the impact of interventions designed to reduce such transmission. Large-scale elimination of paediatric HIV infections appears feasible, although this goal has not yet been fully achieved in KwaZulu-Natal.