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Differentiated service delivery (DSD) models are used to deliver antiretroviral therapy (ART) but data are limited in postpartum women, who are at high risk of non-adherence and elevated viral load (VL) over the extended postpartum period.Randomized controlled trial.We enrolled consecutive postpartum women who initiated ART during pregnancy and met local DSD eligibility (clinically stable, VL less than 400 copies/ml) at a large primary healthcare (PHC) clinic. Women were randomized to a community-based 'adherence club' (AC, the local DSD model: community health worker-led groups of 20-30 patients with ART dispensing at a community venue) or routine PHC clinics (local standard of care with nurse/doctor-led services). Follow-up visits with VL separate from routine care took place at 3, 6, 12, 18 and 24 months postpartum. Endpoints were time to VL of at least 1000 copies/ml (primary) and VL of at least 50 copies/ml (secondary) by intention-to-treat.At enrolment ( n = 409), the median duration postpartum was 10 days, all women had a VL less than 1000 copies/ml and 88% had a VL less than 50 copies/ml; baseline characteristics did not differ by arm. Twenty-four-month retention was 89%. Sixteen and 29% of women in AC experienced a VL of at least 1000 copies/ml by 12 and 24 months, compared to 23 and 37% in PHC, respectively (hazard ratio [HR] = 0.71; 95% confidence interval [CI] = 0.50-1.01). Thirty-two and 44% of women in ACs had a VL of at least 50 copies/ml by 12 and 24 months, compared to 42 and 56% in PHC, respectively (HR = 0.68; 95% CI = 0.51-0.91).Early DSD referral was associated with reduced viraemia through 24 months postpartum and may be an important strategy to improve maternal virologic outcomes.

Patients stable on antiretroviral therapy (ART) may require transfer between health care facilities to maintain continuous care, yet data on the frequency, predictors, and virologic outcomes of transfers are limited.Data for all viral load (VL) testing at public sector health facilities in the Western Cape Province (2011-2018) were obtained. Participant inclusion criteria were a first VL between 2011 and 2013, age15 years at ART initiation, and1 VL within 5 years of ART initiation, of which ≥1 was at a primary health care facility. Two successive VLs taken at different facilities indicated a transfer. We assessed predictors of transfer using generalized estimating equations with Poisson regression and the association between transfer and subsequent VL1000 copies/mL using generalized mixed effects.Overall 84,814 participants (median age at ART initiation 34 years and 68% female) were followed up for up to 4.5 years after their first VL: 34% (n = 29,056) transferred at least once, and among these, 26% transferred twice and 11% transferred thrice or more. Female sex, age30 years, and first VL1000 copies/mL were independently associated with an increased rate of transfer [adjusted rate ratio 1.24, 95% confidence interval (CI): 1.21 to 1.26; 1.34, 95% CI: 1.31 to 1.36; and 1.42, 95% CI: 1.38 to 1.45, respectively]. Adjusting for age, sex, and disengagement, transfer was associated with an increased relative odds of VL1000 copies/mL (odds ratio 1.35, 95% CI: 1.29 to 1.42).Approximately one-third of participants transferred and virologic outcomes were poor post-transfer. Stable patients who transfer may require additional support to maintain adherence.

Background There are few data on the utility of tenofovir diphosphate (TFV-DP) in dried blood spots (DBSs) to predict future viral load (VL) in postpartum women with HIV on antiretroviral therapy (ART). Methods We conducted a nested case-control study within a trial of postpartum ART delivery strategies. Participants started ART containing tenofovir disoproxil fumarate (TDF) in pregnancy, were Results 61 cases and 20 controls contributed 365 DBS-VL pairs (median ART duration, 16 months). Sensitivity and specificity of TFV-DP Conclusions TFV-DP concentrations in DBSs were strongly associated with future viremia and appear useful to identify nonadherence and predict future elevated VL.

Background We investigated the association between travel and viraemia in post-partum women with human immunodeficiency virus on antiretroviral therapy (ART). Methods Data are from a trial of post-partum ART delivery strategies. Women who initiated ART during pregnancy, were clinically stable with a viral load (VL) Results Among 402 women (mean age 29 y, 35% born in the Western Cape), 69% reported one or more travel events over 24 months. Being born beyond the Western Cape (adjusted odds ratio [aOR] 2.03 [95% confidence interval {CI} 1.49 to 2.77]), duration post-partum in months (aOR 1.03 [95% CI 1.02 to 1.05]) and living with the child (aOR 0.60 [95% CI 0.38 to 0.93]) were associated with travel. In multivariable analyses, a travel event was associated with a 92% increase in the odds of a VL ≥400 copies/ml (aOR 1.92 [95% CI 1.19 to 3.10]). Conclusions Interventions to support women on ART who travel are urgently required.

BackgroundLeptospirosis is an emerging zoonosis of global importance. In South Africa, the infection is an underreported public health concern, with limited information on its incidence and distribution. This study aimed to determine the incidence of human leptospirosis from 2010 to 2019 in Western Cape Province (WPC), and to compare the incidence based on seasonal and demographic factors.MethodsA retrospective study was conducted with data on leptospirosis diagnoses by sex, age, season, and year in WCP obtained from the National Health Laboratory Services. With the provincial population sizes as the denominator, the incidence of leptospirosis was estimated and expressed as cases per 100,000 population. Negative binomial regression was used to estimate the effect of sex, season, and year on the incidence of leptospirosis.ResultsA total of 254 cases of leptospirosis were reported between 2010 and 2019, with the highest number of cases being in 2015. The annual incidence ranged between 0.15 and 0.66/100,000 population with a 10-year average incidence of 0.40/100,000 population. The incidence was higher among males than in females (0.55 vs. 0.25/100,000 population; incidence rate ratio (IRR) 2.2, 95% CI: 1.66,3.03). The 18-44 age cohort and had the highest average incidence (0.56/100,000 population), while the ≤17age cohort had the lowest incidence (0.07/100,000 population). The 18-44 (IRR 8.0, 95% CI: 4.65,15.15) and ≥45 (IRR 7.4, 95% CI: 4.17,14.17) age cohorts were more at risk of infection compared to ≤17age cohort. The average incidence of the infection was similar among seasons and there was no significant association between season and incidence of leptospirosis.ConclusionsThe results highlight that leptospirosis is an important zoonosis within the province disproportionately affecting males and the productive age demographic groups. These findings should enhance targeted prevention and provoke further investigation on the importance of environmental and socioeconomic factors on leptospirosis burden.Author SummaryLeptospirosis is an emerging zoonotic bacterial disease of global importance. Despite its wide distribution, the disease is largely underestimated because its clinical manifestations mimic certain commonly known febrile illnesses such as malaria, influenza, hepatitis, and yellow fever. Leptospirosis burden in South Africa has been suggested to be moderately high however studies on the burden of the infection are lacking. This study sought to determine the incidence and trends of leptospirosis in the Western Cape Province, South Africa between 2010 and 2019. Overall, leptospirosis average incidence was 0.4 cases per 100,000 population (ranging from 0.15 to 0.66 cases per 100,000 population). Leptospirosis incidence was highest among male individuals and among those who were aged 18-years and above, however, the incidence did not differ by seasons. These estimates highlight that leptospirosis is an important zoonotic disease within the province and potentially disproportionately affecting males and productive age demographic groups. Therefore, this indicates the need for an all-encompassing One Health Approach to obtain all relevant information concerning leptospirosis distribution and risk factors in South Africa and in Africa at large to effectively enhance leptospirosis prevention strategies.

Contains fulltext : 283104.pdf (Publisher’s version ) (Open Access) BACKGROUND: Late initiation of antiretrovirals in pregnancy is associated with increased risk of perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy and safety of dolutegravir-based compared with efavirenz-based regimens in mothers and infants. METHODS: DolPHIN-2 was a randomised, open-label trial. Pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating antiretroviral therapy in third trimester were eligible for inclusion. Eligible women were randomly assigned (1:1) to receive either dolutegravir-based (50 mg dolutegravir, 300 mg tenofovir disoproxil fumarate, and either 200 mg emtricitabine in South Africa or 300 mg lamivudine in Uganda) or efavirenz-based (fixed dose combination 600 mg tenofovir disoproxil fumarate plus either emtricitabine in South Africa or lamivudine in Uganda) therapy. The primary efficacy outcome was the time to a viral load of less than 50 copies per mL measured at 6, 12, 24, 48, and 72 weeks postpartum with a Cox model adjusting for viral load and CD4 cell count. Safety endpoints were summarised by the number of women and infants with events. This trial is registered with ClinicalTrials.gov, NCT03249181. FINDINGS: Between Jan 23 and Aug 15, 2018, 280 women were screened for inclusion, of whom 268 (96%) women were randomly assigned: 133 (50%) to the efavirenz group and 135 (50%) to the dolutegravir group. 250 (93%; 125 [50%] in the efavirenz group and 125 [50%] in the dolutegravir group) women were included in the intention-to-treat analysis of efficacy. Median time to viral load of less than 50 copies per mL was 4·1 weeks (IQR 4·0-5·1) in the dolutegravir group compared with 12·1 weeks (10·7-13·3) in the efavirenz group (adjusted hazard ratio [HR] 1·93 [95% CI 1·5-2·5]). At 72 weeks postpartum, 116 (93%) mothers in the dolutegravir group and 114 (91%) in the efavirenz group had a viral load of less than 50 copies per mL. Of 57 (21%) mothers with a severe adverse event, three (2%) in the dolutegravir group and five (4%) in the efavirenz group were related to the drug (dolutegravir drug-related events were one woman each with suicidal ideation, suicide attempt, herpes zoster meningitis; efavirenz drug-related events were one woman each with suicide attempt and liver cirrhosis, and three people with drug-induced liver injury). Of 136 (56%) infants in whom severe adverse events were recorded, none were related to the study drugs. In addition to the three infant HIV infections detected at birth in the dolutegravir group that have been previously reported, an additional transmission in the efavirenz group occurred during breastfeeding despite optimal maternal viral suppression and serial negative infant tests in the first year of life. INTERPRETATION: Dolutegravir was safe and well tolerated, supporting updated WHO treatment recommendations in pregnant and breastfeeding women. Infant HIV transmissions can occur during breastfeeding despite persistently undetectable maternal viral load highlighting the need for continued infant testing. FUNDING: Unitaid.

Background Two weeks’ isolation is widely recommended for people commencing treatment for pulmonary tuberculosis (TB). The evidence that this corresponds to clearance of potentially infectious tuberculous mycobacteria in sputum is not well established. This World Health Organization–commissioned review investigated sputum sterilisation dynamics during TB treatment. Methods and findings For the main analysis, 2 systematic literature searches of OvidSP MEDLINE, Embase, and Global Health, and EBSCO CINAHL Plus were conducted to identify studies with data on TB infectiousness (all studies to search date, 1 December 2017) and all randomised controlled trials (RCTs) for drug-susceptible TB (from 1 January 1990 to search date, 20 February 2018). Included articles reported on patients receiving effective treatment for culture-confirmed drug-susceptible pulmonary TB. The outcome of interest was sputum bacteriological conversion: the proportion of patients having converted by a defined time point or a summary measure of time to conversion, assessed by smear or culture. Any study design with 10 or more particpants was considered. Record sifting and data extraction were performed in duplicate. Random effects meta-analyses were performed. A narrative summary additionally describes the results of a systematic search for data evaluating infectiousness from humans to experimental animals (PubMed, all studies to 27 March 2018). Other evidence on duration of infectiousness—including studies reporting on cough dynamics, human tuberculin skin test conversion, or early bactericidal activity of TB treatments—was outside the scope of this review. The literature search was repeated on 22 November 2020, at the request of the editors, to identify studies published after the previous censor date. Four small studies reporting 3 different outcome measures were identified, which included no data that would alter the findings of the review; they are not included in the meta-analyses. Of 5,290 identified records, 44 were included. Twenty-seven (61%) were RCTs and 17 (39%) were cohort studies. Thirteen studies (30%) reported data from Africa, 12 (27%) from Asia, 6 (14%) from South America, 5 (11%) from North America, and 4 (9%) from Europe. Four studies reported data from multiple continents. Summary estimates suggested smear conversion in 9% of patients at 2 weeks (95% CI 3%–24%, 1 single study [N = 1]), and 82% of patients at 2 months of treatment (95% CI 78%–86%, N = 10). Among baseline smear-positive patients, solid culture conversion occurred by 2 weeks in 5% (95% CI 0%–14%, N = 2), increasing to 88% at 2 months (95% CI 84%–92%, N = 20). At equivalent time points, liquid culture conversion was achieved in 3% (95% CI 1%–16%, N = 1) and 59% (95% CI 47%–70%, N = 8). Significant heterogeneity was observed. Further interrogation of the data to explain this heterogeneity was limited by the lack of disaggregation of results, including by factors such as HIV status, baseline smear status, and the presence or absence of lung cavitation. Conclusions This systematic review found that most patients remained culture positive at 2 weeks of TB treatment, challenging the view that individuals are not infectious after this interval. Culture positivity is, however, only 1 component of infectiousness, with reduced cough frequency and aerosol generation after TB treatment initiation likely to also be important. Studies that integrate our findings with data on cough dynamics could provide a more complete perspective on potential transmission of Mycobacterium tuberculosis by individuals on treatment. Trial registration Systematic review registration: PROSPERO 85226., Author summary Why was this study done? Though cited in many countries’ national guidance, the evidence that individuals with pulmonary tuberculosis (TB) are rendered non-infectious by 2 weeks of effective TB treatment is challenged. This systematic review was commissioned by the World Health Organization to provide evidence to inform TB infection prevention and control guidelines. We sought to synthesise the available data on the clearance of potentially infectious TB bacteria from the sputum of patients after starting effective treatment. What did the researchers do and find? We performed systematic searches of literature databases to identify relevant articles, using predetermined inclusion criteria. Extracted data were synthesised using narrative summaries and meta-analyses. A minority of patients had clearance of TB bacteria from sputum at 2 weeks of effective treatment, as assessed by either sputum smear or culture. As expected, the proportion having cleared TB bacteria from sputum increased over time; however, at 2 months of treatment 12% and 41% of patients still had viable TB bacteria present, as assessed by solid and liquid culture, respectively. What do these findings mean? The presence of viable TB bacteria in the sputum of pulmonary TB patients beyond 2 weeks of effective treatment suggests individuals may be infectious for longer than this interval. TB transmission requires the presence of viable mycobacteria in sputum and a mechanism for aerosol or droplet spread. Understanding how other factors, such as the presence of cough, change during treatment is also important for TB infection prevention and control.

The burden of chronic conditions is increasing rapidly in low- and middle-income countries. Chronic conditions require long-term and continuous care, including for patients transferring between facilities. Patient transfer is particularly important in the context of health service decentralization, which has led to increasing numbers of primary care facilities at which patients can access care, and high levels of migration, which suggest that patients might require care at multiple facilities. This article provides a critical review of existing evidence regarding transfer of stable patients receiving primary care for chronic conditions. Patient transfer has received limited consideration in people living with HIV, with growing concern that patients who transfer are at risk of poor outcomes; this appears similar for people with TB, although studies are few. There are minimal data on transfer of patients with non-communicable diseases, including diabetes. Patient transfer for chronic conditions has thus received surprisingly little attention from researchers; considering the potential risks, more research is urgently required regarding reasons for and outcomes of transfers, transfer processes and interventions to optimize transfers, for different chronic conditions. Ultimately, it is the responsibility of health systems to facilitate successful transfers, and this issue requires increased attention from researchers and policy-makers.

Introduction: The World Health Organization recommends initiation of lifelong antiretroviral therapy (ART) in all HIV-infected pregnant women (“Option B+''); however, disengagement from care has been documented postnatally and thereafter. The community-based adherence club (AC) system has been widely implemented in Cape Town, South Africa, and provides HIV care to stable adults on ART, but women who initiated ART in antenatal care services are currently referred to local ART clinics postnatally. Methods: The Postpartum Adherence Clubs for Antiretroviral Therapy (PACART) study is a pragmatic randomised controlled trial evaluating ACs to deliver long-term HIV care to women who initiated ART antenatally. Consecutive eligible women seeking care postnatally at a large primary health care facility in Cape Town were randomised to either the local ART clinic (standard of care), or the AC service. The primary objective is to compare maternal HIV viral suppression up to 24 months postpartum. Six study visits are scheduled through 24 months; measurements at each visit include phlebotomy for viral load and questionnaires assessing maternal health, infant health, and ART adherence. Qualitative interviews examining issues of ART adherence and retention, and assessments of costs and cost-effectiveness will also be done. Results: Enrolment is complete, with 412 women enrolled. Follow-up visits are ongoing. Discussion: There is an urgent need to improve ART delivery for maternal and child health. With a pragmatic trial design, we aim to assess use of the community-based AC system to improve maternal engagement in HIV care in the postpartum period and beyond. Keywords: Adherence clubs, Antiretroviral therapy, HIV, Option B+, Postpartum, Pregnancy