Hospitalization among infants who initiate antiretroviral therapy before 3 months of age.

INTRODUCTION: Studies examining hospitalization among infants with HIV in resource-limited settings, in the context of early infant diagnosis and early antiretroviral therapy (ART) initiation, are limited. METHODS: We used routinely collected data on infants who initiated ART aged <3 months (Western Cape province, South Africa; 2013-2017) to describe hospitalization from birth until 12 months post-ART initiation. Record reviews were additionally performed at three tertiary-level facilities. We used mixed-effects Poisson regression to examine factors associated with hospitalization. RESULTS: Among 840 infants, 579 (69%) were hospitalized; 36% had >1 hospitalization. Median age at ART initiation decreased from 57 days (interquartile range [IQR] 22-74; 2013-2015) to 19 days (IQR 5-54; 2016-2017). Early neonatal hospitalization (age <7 days) occurred in 271 infants (32%) and represented 24% of hospitalizations (272/1131). Overall, 443 infants (53%) were hospitalized at age ≥7 days, including 13% with hospitalizations pre-ART initiation, 15% pre and post-ART initiation and 25% post-ART initiation. Excluding early neonatal hospitalizations, initiating ART at older age vs. age <1 week was associated with higher hospitalization rates: adjusted incidence rate ratios (95% confidence interval) were 1.86 (1.31-2.64); 2.31 (1.62-3.29) and 2.47 (1.76-3.46) if ART initiation age was 1-4 weeks; 5-8 weeks and 9-12 weeks respectively. Among infants whose hospital records were reviewed, reasons for early neonatal hospitalizations mostly related to prematurity or low birthweight (n = 46/60; 77%) whereas hospitalizations at age ≥7 days were mostly due to infections (n = 206/243; 85%). CONCLUSIONS: Earlier ART initiation is associated with lower hospitalization rates. High hospitalization rates, despite initiation age <3 months, is concerning.

Variations in the characteristics and outcomes of children living with HIV following universal ART in sub-Saharan Africa (2006-17): a retrospective cohort study.

BACKGROUND: The proportion of children living with HIV and receiving antiretroviral therapy (ART) in sub-Saharan Africa has increased greatly since 2006, yet the changes in their demographic characteristics and treatment outcomes have not been well described. We examine the trends in characteristics and outcomes of children living with HIV who were younger than 5 years at ART initiation, and compare outcomes over time and across country income groups. METHODS: We conducted a retrospective cohort analysis of data from children living with HIV who were younger than 5 years at ART initiation from 45 paediatric sites in 16 low-income, lower-middle-income, and upper-middle-income countries in sub-Saharan Africa (Benin, Burundi, Côte d'Ivoire, Democratic Republic of the Congo, Ghana, Kenya, Lesotho, Malawi, Mali, Mozambique, Rwanda, South Africa, Togo, Uganda, Zambia, and Zimbabwe). Outcomes were trends in patient characteristics at ART initiation (age, weight, height, and CD4%), and comparisons of mortality and loss to follow-up during ART over time and in various economic settings. We identified risk factors for mortality using Cox proportional hazards models. Each participating region had relevant institutional ethics review board approvals to contribute data to the analysis. FINDINGS: We included 32 221 children living with HIV and initiating ART younger than 5 years between Jan 1, 2006, and Dec 31, 2017. Median age at ART initiation was 20·4 months (IQR 9·4-36·0) in 2006-10, 19·2 months (8·3-33·6) in 2011-13, and 19·2 months (8·8-33·7) in 2014-17. Median age at ART initiation was 13·2 months (IQR 4·7-26·8) in upper-middle-income countries, 22·6 months (13·2-37·5) in lower-middle-income countries and 24·2 months (13·5-39·1) in low-income countries. The proportion of children initiating ART younger than 3 months increased from 770 (5·1%) of 14 943 children in 2006-10 to 728 (10·0%) of 7290 children in 2014-17. The proportion of children initiating ART with severe immunosuppression decreased from 5469 (74·7%) of 7314 children for whom CD4% data were available in 2006-10 to 2353 (55·2%) of 4269 children in 2014-17. Mortality at 24 months on ART decreased from 970 (6·5%) of 14 943 children in 2006-10 to 214 (2·9%) of 7290 children in 2014-17. Loss to follow-up was 20·5% (95% CI 20·1-21·0) overall, and was similar across time periods. In multivariable analysis, lower mortality was observed for more recent ART initiation cohorts (adjusted hazard ratio 0·70, 95% CI 0·63-0·79 for 2011-13; 0·53, 0·45-0·72 for 2014-17 vs 2006-10) and for those residing in an upper-middle-income country (0·42, 0·35-0·49 vs low-income countries). INTERPRETATION: Mortality declined significantly after universal ART recommendations for children younger than 2 years in 2010 and children younger than 5 years in 2013. However, substantial variations persisted across country income groups, and one in five children continue to be lost to follow-up. Targeted interventions are required to improve outcomes of children living with HIV, especially in the poorest countries. FUNDING: National Institute of Allergy and Infectious Disease.

Provider- and patient-level costs associated with providing antiretroviral therapy during the postpartum phase to women living with HIV in South Africa: A cost comparison of three postpartum models of care.

OBJECTIVE: To compare the unit and total costs of three models of ART care for mother-infant pairs during the postpartum phase from provider and patient's perspectives: (i) local standard of care with women in general ART services and infants at well-baby clinics; (ii) women and infants continue to receive care through an integrated maternal and child care approach during the postpartum breastfeeding period; and (iii) referral of women directly to community adherence clubs with their infants receiving care at well-baby clinics. METHODS: Capital and recurrent cost data (relating to buildings, furniture, equipment, personnel, overheads, maintenance, medication, diagnostic tests and immunisations) were collected from a provider's perspective at six sites in Cape Town, South Africa. Patient time, collected via time-and-motion observation and questionnaires, was used to estimate patient perspective costs and is comprised of lost productivity time, time spent travelling and the direct cost of travelling. RESULTS: The cost of postpartum ART visits under models I, II and III was US $13, US $10 and US $7 per visit for a mother-infant pair, respectively, in 2018 US$. The annual costs for the mother-infant pair utilising the average visit frequencies (a mean of 4.5, 6.9 and 6.7 visits postpartum for models I, II and III, respectively) including costs for infant immunisations, visits, medication and diagnostic tests for both mothers and infants were: I - US $222, II - US $335 and III - US $249. Sensitivity analysis to assess the impact of visit frequency on visit cost showed that Model I annual costs would be most costly if visit frequency was equalised. CONCLUSION: This comparative analysis of three models of care provides novel data on unit costs and insight into the costs to provide ART and care to mother-infant pairs during the delicate postpartum phase. These costs may be used to help make decisions around integrated services models and differentiated service delivery for postpartum WLH and their children.

OBJECTIF: Comparer le coût et unitaire et total de trois modèles de soins ART pour les paires mère-enfant pendant la phase post-partum selon les perspectives du fournisseur et du patient: (I) - normes locales des soins avec les femmes dans les services généraux de l'ART et les nourrissons dans les cliniques de bien-être pour bébés; (II) - les femmes et les nourrissons continuent de recevoir des soins via une approche intégrée de soins maternels et infantiles pendant la période d'allaitement post-partum; et (III) - orientation des femmes directement vers les clubs d'adhésion communautaires, leurs nourrissons recevant des soins dans les cliniques de bien-être pour bébés pour bébés. MÉTHODES: Les données sur les coûts d'investissement et les coûts récurrents (relatifs aux bâtiments, au mobilier, à l'équipement, au personnel, aux frais généraux, à l'entretien, aux médicaments, aux tests de diagnostic et aux vaccinations) ont été recueillies selon le point de vue du prestataire sur six sites à Cape Town, en Afrique du Sud. Le temps du patient, recueilli via l'observation du temps et des mouvements et des questionnaires, a été utilisé pour estimer les coûts selon le point de vue du patient, et comprend le temps de productivité perdu, le temps passé en déplacement et le coût direct du déplacement. RÉSULTATS: Le coût des visites ART post-partum dans les modèles I, II et III était respectivement de 13 USD, 10 USD et 7 USD par visite pour une paire mère-enfant en USD de 2018. Les coûts annuels pour la paire mère-enfant en utilisant la fréquence moyenne des visites (une moyenne de 4,5 ; 6,9 et 6,7 visites post-partum pour les modèles I, II et III respectivement), y compris les coûts des vaccinations infantiles, des visites, des médicaments et des tests diagnostiques pour les mères et les nourrissons étaient: I - 222 USD, II - 335 USD et III - 249 USD. L'analyse de sensibilité pour évaluer l'impact de la fréquence des visites sur le coût des visites a montré que les coûts annuels du modèle I seraient les plus élevés si la fréquence des visites était égalisée. CONCLUSIONS: Cette analyse comparative de trois modèles de soins fournit de nouvelles données sur les coûts unitaires et un aperçu des coûts de fourniture de l'ART et de soins aux paires mère-enfant pendant la phase délicate du post-partum. Ces coûts peuvent être utilisés pour aider à la prise des décisions concernant les modèles de services intégrés et la prestation de services différenciés pour les femmes en période de post-partum et leurs enfants.

Community-based adherence clubs for postpartum women on antiretroviral therapy (ART) in Cape Town, South Africa: a pilot study.

BACKGROUND: With an increasing number of countries implementing Option B+ guidelines of lifelong antiretroviral therapy (ART) for all pregnant and breastfeeding women, there is urgent need to identify effective approaches for retaining this growing and highly vulnerable population in ART care. METHODS: Newly postpartum, breastfeeding women who initiated ART in pregnancy and met eligibility criteria were enrolled, and offered the choice of two options for postpartum ART care: (i) referral to existing network of community-based adherence clubs or (ii) referral to local primary health care clinic (PHC). Women were followed at study measurement visits conducted separately from either service. Primary outcome was a composite endpoint of retention in ART services and viral suppression [VS < 50 copies/mL based on viral load (VL) testing at measurement visits] at 12 months postpartum. Outcomes were compared across postpartum services using chi-square, Fisher's exact tests and Poisson regression models. The primary outcome was compared across services where women were receiving care at 12 months postpartum in exploratory analyses. RESULTS: Between February and September 2015, 129 women (median age: 28.9 years; median time postpartum: 10 days) were enrolled with 65% opting to receive postpartum HIV care through an adherence club. Among 110 women retained at study measurement visits, 91 (83%) achieved the composite endpoint, with no difference between those who originally chose clubs versus those who chose PHC services. Movement from an adherence club to PHC services was common: 31% of women who originally chose clubs and were engaged in care at 12 months postpartum were attending a PHC service. Further, levels of VS differed significantly by where women were accessing ART care at 12 months postpartum, regardless of initial choice: 98% of women receiving care in an adherence club and 76% receiving care at PHC had VS < 50 copies/mL at 12 months postpartum (p = 0.001). CONCLUSION: This study found comparable outcomes related to retention and VS at 12 months postpartum between women choosing adherence clubs and those choosing PHC. However, movement between postpartum services among those who originally chose adherence clubs was common, with poorer VS outcomes among women leaving clubs and returning to PHC services. TRIAL REGISTRATION: ClinicalTrials.gov NCT02417675 , April 16, 2015 (retrospectively registered).

Earlier Antiretroviral Therapy Initiation and Decreasing Mortality Among HIV-infected Infants Initiating Antiretroviral Therapy Within 3 Months of Age in South Africa, 2006-2017.

BACKGROUND: Early infant diagnosis of HIV and antiretroviral therapy (ART) has been rapidly scaled-up. We aimed to examine the effect of expanded access to early ART on the characteristics and outcomes of infants initiating ART. METHODS: From 9 cohorts within the International epidemiologic Databases to Evaluate AIDS-Southern Africa collaboration, we included infants with HIV initiating ART ≤3 months of age between 2006 and 2017. We described ART initiation characteristics and the probability of mortality, loss to follow-up (LTFU) and transfer out after 6 months on ART and assessed factors associated with mortality and LTFU. RESULTS: A total of 1847 infants started ART at a median age of 60 days [interquartile range: 29-77] and CD4 percentage (%) of 27% (18%-38%). Across ART initiation calendar periods 2006-2009 to 2013-2017, ART initiation age decreased from 68 (53-81) to 45 days (7-71) (P < 0.001), median CD4% improved from 22% (15%-34%) to 32% (22-43) (P < 0.001) and the proportion with World Health Organization clinical disease stage 3 or 4 declined from 81.6% to 32.7% (P < 0.001). Overall, the 6-month mortality probability was 5.0% and LTFU was 20.4%. Mortality was 10.6% (95% confidence interval: 7.8%-14.4%) in 2006-2009 and 4.6% (3.1%-6.7%) in 2013-2017 (P < 0.001), with similar LTFU across calendar periods (P = 0.274). Pretreatment weight-for-age Z score <-2 was associated with higher mortality. CONCLUSIONS: Infants with HIV are starting ART younger and healthier with associated declines in mortality. However, the risk of mortality remained undesirably high in recent years. Focused interventions are needed to optimize the benefits of earlier diagnosis and treatment.

Experiences of HIV-positive postpartum women and health workers involved with community-based antiretroviral therapy adherence clubs in Cape Town, South Africa.

BACKGROUND: The rollout of universal, lifelong treatment for all HIV-positive pregnant and breastfeeding women ("Option B+") has rapidly increased the number of women initiating antiretroviral treatment (ART) and requiring ART care postpartum. In a pilot project in South Africa, eligible postpartum women were offered the choice of referral to the standard of care, a local primary health care clinic, or a community-based model of differentiated ART services, the adherence club (AC). ACs have typically enrolled only non-pregnant and non-postpartum adults; postpartum women had not previously been referred directly from antenatal care. There is little evidence regarding postpartum women's preferences for and experiences of differentiated models of care, or the capacity of this particular model to cater to their specific needs. This qualitative paper reports on feedback from both postpartum women and health workers who care for them on their respective experiences of the AC. METHODS: One-on-one in-depth qualitative interviews were conducted with 19 (23%) of the 84 postpartum women who selected the AC and were retained at approximately 12 months postpartum, and 9 health workers who staff the AC. Data were transcribed and thematically analysed using NVivo 11. RESULTS: Postpartum women's inclusion in the AC was acceptable for both participants and health workers. Health workers were welcoming of postpartum women but expressed concerns about prospects for longer term adherence and retention, and raised logistical issues they felt might compromise trust with AC members in general. CONCLUSIONS: Enrolling postpartum women in mixed groups with the general adult population is feasible and acceptable. Preliminary recommendations are offered and may assist in supporting the specific needs of postpartum women transitioning from antenatal ART care. TRIAL REGISTRATION: Number NCT02417675 clinicaltrials.gov/ct2/show/record/NCT02417675 (retrospective reg.).

Prevalence and determinants of unplanned pregnancy in HIV-positive and HIV-negative pregnant women in Cape Town, South Africa: a cross-sectional study.

OBJECTIVES: Prevention of unplanned pregnancy is a crucial aspect of preventing mother-to-child HIV transmission. There are few data investigating how HIV status and use of antiretroviral therapy (ART) may influence pregnancy planning in high HIV burden settings. Our objective was to examine the prevalence and determinants of unplanned pregnancy among HIV-positive and HIV-negative women in Cape Town, South Africa. DESIGN: Cross-sectional analysis. SETTINGS: Single primary-level antenatal care clinic in Cape Town, South Africa. PARTICIPANTS: HIV-positive and HIV-negative pregnant women, booking for antenatal care from March 2013 to August 2015, were included. MAIN OUTCOME MEASURES: Unplanned pregnancy was measured at the first antenatal care visit using the London Measure of Unplanned Pregnancy (LMUP). Analyses examined LMUP scores across four groups of participants defined by their HIV status, awareness of their HIV status prior to the current pregnancy and/or whether they were using antiretroviral therapy (ART) prior to the current pregnancy. RESULTS: Among 2105 pregnant women (1512 HIV positive; 593 HIV negative), median age was 28 years, 43% were married/cohabiting and 20% were nulliparous. Levels of unplanned pregnancy were significantly higher in HIV-positive versus HIV-negative women (50% vs 33%, p<0.001); and highest in women who were known HIV positive but not on ART (53%). After adjusting for age, parity and marital status, unplanned pregnancy was most common among women newly diagnosed and women who were known HIV positive but not on ART (compared with HIV-negative women, adjusted OR (aOR): 1.43; 95% CI 1.05 to 1.94 and aOR: 1.57; 95% CI 1.13 to 2.15, respectively). Increased parity and younger age (<24 years) were also associated with unplanned pregnancy (aOR: 1.42; 95% CI 1.25 to 1.60 and aOR: 1.83; 95% CI 1.23 to 2.74, respectively). CONCLUSIONS: We observed high levels of unplanned pregnancy among HIV-positive women, particularly among those not on ART, suggesting ongoing missed opportunities for improved family planning and counselling services for HIV-positive women.

Differentiated models of care for postpartum women on antiretroviral therapy in Cape Town, South Africa: a cohort study.

BACKGROUND: The numbers of women initiating lifelong antiretroviral therapy (ART) during pregnancy and postpartum is increasing rapidly, presenting a burden on health systems and an urgent need for scalable models of care for this population. In a pilot project, we referred postpartum women who initiated ART during pregnancy to a community-based model of differentiated ART services. METHODS: Eligible women (on ART for at least 3 months with viral load (VL)<1000 copies/mL) were offered a choice of two ART models of care: (i) referral to an existing system of community-based 'adherence clubs', operated by lay counsellors with medication collection every 2-4 months; or (ii) referral to local primary healthcare clinics (PHC) with services provided by clinicians and medication collection every 1-2 months (local standard of care for postpartum ART). For evaluation, women were followed through 6-months postpartum with VL testing separate from either ART service. RESULTS: Through September 2015, n = 129 women were enrolled (median age, 28 years; median time postpartum, 10 days). Overall, 65% (n = 84) chose adherence clubs and 35% (n = 45) chose PHCs; there were no demographic or clinical predictors of this choice. Location of service delivery was commonly cited as a reason for choice by women selecting either model of care; shorter waiting times, ability to receive ART from lay counsellors and less frequent appointments were motivations for choosing adherence clubs. Among women choosing adherence clubs, 15% never attended the service and another 11% attended the service but were not retained through six months postpartum. Overall, 86% of women (n = 111) remained in the evaluation through 6 months postpartum; in this group, there were no differences in VL<1000 copies/mL at six months postpartum between women choosing PHCs (88%) vs. adherence clubs (92%; p = 0.483), but women who were not retained in adherence clubs were more likely to have VL≥1000 copies/mL compared to those who remained (p = 0.002). DISCUSSION: Adherence clubs may be a valuable model for postpartum women initiating ART in pregnancy, with good short-term outcomes observed during this critical period. To support optimal implementation, further research is needed into patient preferences for models of care, with consideration of integration of maternal and child health services, while ART adherence and retention require ongoing consideration in this population.