Fidelity of implementation of national guidelines on malaria diagnosis for children under-five years in Rivers State, Nigeria.

BACKGROUND: Malaria is still a disease of global public health importance and children under-five years of age are the most vulnerable to the disease. Nigeria adopted the "test and treat" strategy in the national malaria guidelines as one of the ways to control malaria transmission. The level of adherence to the guidelines is an important indicator for the success or failure of the country's roadmap to malaria elimination by 2030. This study aimed to assess the fidelity of implementation of the national guidelines on malaria diagnosis for children under-five years and examine its associated moderating factors in health care facilities in Rivers State, Nigeria. METHODS: This was a descriptive, cross-sectional study conducted in Port Harcourt metropolis. Data were collected from 147 public, formal private and informal private health care facilities. The study used a questionnaire developed based on Carroll's Conceptual Framework for Implementation Fidelity. Frequency, mean and median scores for implementation fidelity and its associated factors were calculated. Associations between fidelity and the measured predictors were examined using Mann Whitney U test, Kruskal Wallis test, and multiple linear regression modelling using robust estimation of errors. Regression results are presented in adjusted coefficient (ß) and 95% confidence intervals. RESULTS: The median (IQR) score fidelity score for all participants was 65% (43.3, 85). Informal private facilities (proprietary patent medicine vendors) had the lowest fidelity scores (47%) compared to formal private (69%) and public health facilities (79%). Intervention complexity had a statistically significant inverse relationship to implementation fidelity (ß = - 1.89 [- 3.42, - 0.34]). Increase in participant responsiveness (ß = 8.57 [4.83, 12.32]) and the type of malaria test offered at the facility (e.g., RDT vs. no test, ß = 16.90 [6.78, 27.03]; microscopy vs. no test, ß = 21.88 [13.60, 30.16]) were positively associated with fidelity score. CONCLUSIONS: This study showed that core elements of the "test and treat" strategy, such as testing all suspected cases with approved diagnostic methods before treatment, are still not fully implemented by health facilities. There is a need for strategies to increase fidelity, especially in the informal private health sector, for malaria elimination programme outcomes to be achieved.

Test-treat-track-test-treat (5T) approach for Schistosoma haematobium elimination on Pemba Island, Tanzania.

BACKGROUND: After decades of praziquantel mass drug administration (MDA), several countries approach schistosomiasis elimination. Continuing MDA in largely uninfected populations no longer seems justified. Alternative interventions to maintain the gains or accelerate interruption of transmission are needed. We report results, strengths, and shortcomings of novel test-treat-track-test-treat (5T) interventions in low Schistosoma haematobium prevalence areas on Pemba, Tanzania. METHODS: School- and household-based surveys were conducted in 2021 and 2022 to monitor the S. haematobium and microhematuria prevalence and assess the impact of interventions. In 2021, 5T interventions were implemented in 15 low-prevalence areas and included: (i) testing schoolchildren in primary and Islamic schools for microhematuria as a proxy for S. haematobium, (ii) treating positive children, (iii) tracking them to their households and to water bodies they frequented, (iv) testing individuals at households and water bodies, and (v) treating positive individuals. Additionally, test-and-treat interventions were implemented in the 22 health facilities of the study area. RESULTS: The S. haematobium prevalence in the school-based survey in 15 low-prevalence implementation units was 0.5% (7/1560) in 2021 and 0.4% (6/1645) in 2022. In the household-based survey, 0.5% (14/2975) and 0.7% (19/2920) of participants were infected with S. haematobium in 2021 and 2022, respectively. The microhematuria prevalence, excluding trace results, in the school-based survey was 1.4% (21/1560) in 2021 and 1.5% (24/1645) in 2022. In the household-based survey, it was 3.3% (98/2975) in 2021 and 5.4% (159/2920) in 2022. During the 5T interventions, the microhaematuria prevalence was 3.8% (140/3700) and 5.8% (34/594) in children in primary and Islamic schools, respectively, 17.1% (44/258) in household members, and 16.7% (10/60) in people at water bodies. In health facilities, 19.8% (70/354) of patients tested microhematuria-positive. CONCLUSIONS: The targeted 5T interventions maintained the very low S. haematobium prevalence and proved straightforward and feasible to identify and treat many of the few S. haematobium-infected individuals. Future research will show whether 5T interventions can maintain gains in the longer-term and expedite elimination. TRIAL REGISTRATION: ISRCTN, ISCRCTN91431493. Registered 11 February 2020, https://www.isrctn.com/ISRCTN91431493 .

Decentralised same day test and treatment of hepatitis C levering existing peer support networks among men who inject drugs: feasibility and effectiveness.

BACKGROUND: Prevalence of hepatitis C virus (HCV) infection among people who inject drugs in the state of Manipur, India, is 43%; however, access to care is poor. We piloted a Community-led and comprehensive hepatitis care model that included same-day HCV treatment at drug treatment centres. METHODS: Screening was conducted through venipuncture samples collected by community peer PWID, using HCV antibody (HCV Ab) rapid screening and hepatitis B virus (HBV) surface antigen (HBsAg) rapid diagnostic tests. Reactive HCV Ab samples were tested for HCV RNA using near point-of-care Truenat® HCV on Truelab® Quattro. Eligible HCV RNA-positive participants were treated on the same day using direct-acting antivirals and followed for sustained virologic response (SVR). HBsAg-negative participants received rapid HBV vaccination regimen while those positive for HBsAg were tested for DNA and referred for treatment. RESULTS: Between November 2021 and August 2022, 643 individuals were approached and 503 consented and were screened. All screened were males with history of injection drug use, and a median age of 27 years (IQR 23-32). Of the 241 (47.9%) HCV Ab reactive all underwent RNA testing and 156 (64.7%) were RNA detectable. Of those with viraemia, 155 (99.4%) were initiated on treatment with 153 (98.1%) on same day, with 2 (1.2%) HBsAg positive and waiting for HBV DNA results. Among those 153, median time from HCV Ab screening to treatment was 6 h 38 min (IQR 5 h 42 min-8 h 23 min). In total 155 (100%) completed HCV treatment, of those 148 (95.5%) completed SVR testing and 130 (87.8%) achieved SVR12. 27 (5%) participants were HBsAg-positive, 3 (11.1%) were also living with HCV viraemia; 443 (97.6%) were eligible for vaccination and 436 (98.4%) received all 3 vaccine doses. CONCLUSION: Community-led hepatitis care incorporating same day "test and treat" for HCV was feasible and effective. HBV screening identified a large proportion who were unvaccinated. Peer support extended resulted in ensuring compliance to care and treatment cascade and completing all the three doses of HBV vaccination. As the screening, diagnostics infrastructure and vaccine are available in most countries with national viral hepatitis programs also in place, our model can be adapted or replicated to progress towards global elimination targets.

Cost-effectiveness of treating all hepatitis B-positive individuals in the United States.

Chronic hepatitis B virus (HBV) infection is a leading cause of liver disease and related mortality globally. However, most of the infected individuals in the United States remain undiagnosed and untreated. There is a need to understand more completely the economic and disease burden impact of removing treatment restrictions and increasing diagnosis and treatment. The PRoGReSs model, a dynamic HBV model that tracks the infected population by year, disease stage, and gender, was used to quantify the disease and economic burden of chronic HBV infection in the United States from 2020 to 2050 based on four scenarios: a status quo (base) scenario and three treat-all scenarios, in which screening, diagnosis, and treatment were maximized at different annual treatment price levels of $5382, $2000 and $750. Compared to the base scenario, the treat-all scenarios would avert 71,100 acute and 11,100 chronic incident cases of HBV, and 169,000 liver-related deaths from 2020 to 2050. At an annual treatment cost of $2000, treating all HBV infections would be highly cost-effective, and at $750 would be cost saving and would achieve a positive return on investment before 2050. Maximizing the diagnosed and treated HBV population in the United States would avert a significant number of cases of advanced liver disease and related mortality. Such interventions can also be cost-effective compared to the status quo strategy, and cost saving at a treatment price threshold of $750 annually, above the current lowest annual treatment cost of $362.

Experiences of healthcare personnel on the efficacy of artemisinin-based combination therapy and malaria diagnosis in hospitals in Uganda.

BACKGROUND: The risk of widespread resistance to artemisinin-based combination therapy (ACT) remains high in Uganda following detection of Plasmodium falciparum parasites with delayed artemisinin clearance genotype and phenotype. Establishment of context specific interventions to mitigate emergence and spread of artemisinin resistance is thus key in the fight against malaria in the country. The aim of this study was to explore the experiences of healthcare personnel on malaria diagnosis and self-reported efficacy of ACT in the management of malaria symptomatic patients in hospitals in low and high malaria transmission settings in Uganda. METHODS: This was a qualitative study in which data was collected from healthcare personnel in hospitals using key informant interviews. The key informant interview guide was developed, pre-tested prior to use and covered the following areas, (i) sociodemographic characteristics, (ii) malaria diagnosis (clinical and parasite based), (iii) quality-assured artemisinin-based combination therapy, (iv) malaria patient follow-up, (v) artemisinin resistance, (vi) anti-malarial self-medication. Data was entered in Atlas.ti ver 9.0 and analysis done following a framework criterion. RESULTS: A total of 22 respondents were interviewed of which 16 (72.7%) were clinicians. Majority, 81.8% (18/22) of the respondents were male. The following themes were developed from the analysis, malaria diagnosis (procedures and challenges), use of malaria laboratory test results, malaria treatment in hospitals, use of quality assured ACT (QAACT) in malaria treatment, and efficacy of ACT in malaria treatment. CONCLUSION: Most healthcare personnel-initiated malaria treatment after a positive laboratory test. Cases of malaria patients who report remaining symptomatic after prior use of ACT exist especially in high malaria transmission settings in Uganda. There is need for regular monitoring of artemisinin resistance emergence and spread in the country.

Testing and treatment for malaria elimination: a systematic review.

BACKGROUND: Global interest in malaria elimination has prompted research on active test and treat (TaT) strategies. METHODS: A systematic review and meta-analysis were conducted to assess the effectiveness of TaT strategies to reduce malaria transmission. RESULTS: A total of 72 empirical research and 24 modelling studies were identified, mainly focused on proactive mass TaT (MTaT) and reactive case detection (RACD) in higher and lower transmission settings, respectively. Ten intervention studies compared MTaT to no MTaT and the evidence for impact on malaria incidence was weak. No intervention studies compared RACD to no RACD. Compared to passive case detection (PCD) alone, PCD + RACD using standard diagnostics increased infection detection 52.7% and 11.3% in low and very low transmission settings, respectively. Using molecular methods increased this detection of infections by 1.4- and 1.1-fold, respectively. CONCLUSION: Results suggest MTaT is not effective for reducing transmission. By increasing case detection, surveillance data provided by RACD may indirectly reduce transmission by informing coordinated responses of intervention targeting.

Differences in Reasons for Late Presentation to HIV Care in Uganda Among Men and Women.

Late presentation to HIV care, i.e., presenting with < 200 CD4 cells/mL, is associated with higher mortality and worse outcomes. Despite that, a quarter of people living with HIV in Uganda still present late to care. We surveyed Ugandans living with HIV who enrolled in clinic ≤ 90 days prior. We compared groups who presented 'late' with CD4 < 200 and 'early' with CD4 > 350, stratifying by sex. We found men who presented late had higher externalized stigma than early presenters. Thirty-six percent of the entire cohort were depressed. Social support was stronger in late presenters versus early, although weak overall. Social support was inversely correlated with depression, with social support dropping as depression increased. Interventions to improve clinic privacy, reduce stigma, improve social support, and help women disclose their HIV status to male partners are needed to reduce late presentation to HIV care.

Linkage to HIV Care and Early Retention in Care Rates in the Universal Test-and-Treat Era: A Population-based Prospective Study in KwaZulu-Natal, South Africa.

HIV linkage, and retention are key weaknesses in South Africa's national antiretroviral therapy (ART) program, with the greatest loss of patients in the HIV treatment pathway occurring before ART initiation. This study investigated linkage-to and early-retention-in-care (LTRIC) rates among adults newly diagnosed with HIV in a high-HIV prevalent rural district. We conducted an observational prospective cohort study to investigate LTRIC rates for adults with a new HIV diagnosis in South Africa. Patient-level survey and clinical data were collected using a one-stage-cluster design from 18 healthcare facilities and triangulated between HIV and laboratory databases and registered deaths from Department of Home Affairs. We used Chi-square tests to assess associations between categorical variables, and results were stratified by HIV status, sex, and age. Of the 5,637 participants recruited, 21.2% had confirmed HIV, of which 70.9% were women, and 46.5% were aged 25-34 years. Although 82.7% of participants were linked-to-care within 3 months, only 46.1% remained-in-care 12 months after initiating ART and 5.2% were deceased. While a significantly higher proportion of men were linked-to-care at 3 months compared to women, a significant proportion of women (49.5%) remained-in-care at 12 months than men (38.0%). Post-secondary education and child support grants were significantly associated with retention. We found high linkage-to-care rates, but less than 50% of participants remained-in-care at 12 months. Significant effort is required to retain people living with HIV in care, especially during the first year after ART initiation. Our findings suggest that interventions could target men to encourage HIV testing.

Reasons for, and factors associated with, positive HIV retesting: a cross-sectional study in Eswatini.

Eswatini has a high HIV prevalence but has made progress towards improving HIV-status awareness, ART uptake and viral suppression. However, there is still a delay in ART initiation, which could partly be attributed to positive HIV-retesting. This study examines reasons for, and factors associated with, positive HIV-retesting among MaxART participants in Eswatini. Data from 601 participants is included in this cross-sectional study. Descriptive statistics and logistic regressions were used. Of the participants, 32.8% has ever retested after a previous positive result. Most participants who retested did this because they could not accept their results (61.9% of all retesters). Other main reasons are related to external influences, gender or the progression of their HIV infection (respectively 18.3%, 10.2%, and 6.1% of all retesters). Participants without a current partner and participants with less time since their first positive test have lower odds of retesting. To decrease retesting and reduce the delay in ART initiation resulting from it, efforts could be made on increasing the acceptance of positive HIV results. Providing more information on the process of testing and importance of early ART initiation, could be part of the solution.

HIV care continuum outcomes among recently diagnosed people with HIV (PWH) in Washington, DC.

The Ending the HIV Epidemic initiative aims to decrease new HIV infections and promote test-and-treat strategies. Our aims were to establish a baseline of HIV outcomes among newly diagnosed PWH in Washington, DC (DC), a 'hotspot' for the HIV epidemic. We also examined sociodemographic and clinical factors associated with retention in care (RIC), antiretroviral therapy (ART) initiation and viral suppression (VS) among newly diagnosed PWH in the DC Cohort from 2011-2016. Among 455 newly diagnosed participants, 92% were RIC at 12 months, ART was initiated in 65% at 3 months and 91% at 12 months, VS in at least 17% at 3 months and 82% at 12 months and 55% of those with VS at 12 months had sustained VS for an additional 12 months. AIDS diagnosis was associated with RIC (aOR 2.99; 1.13-2.28), ART initiation by 3 months (aOR 2.58; 1.61-4.12) and VS by 12 months (aOR4.87; 1.69-14.03). This analysis contributes to our understanding of the HIV treatment dynamics of persons with recently diagnosed HIV infection in a city with a severe HIV epidemic.

Enhancing linkage to HIV care in the "Universal Test and Treat" era: Barriers and enablers to HIV care among adults in a high HIV burdened district in KwaZulu-Natal, South Africa.

Ending AIDS by 2030 would depend on how successful health systems are in linking people living with HIV (PLHIV) into care. The World Health Organization recommended the 'Universal Test and Treat' (UTT) strategy - initiating all individuals testing positive on antiretroviral therapy (ART) irrespective of their CD4 count and clinical staging. This study aimed to explore the enablers and barriers to linkage to HIV care among adults with a new HIV diagnosis in a high-HIV prevalent rural district in South Africa. A qualitative study was undertaken to explore patients' perceptions of enablers and barriers of linkage-to-care, using a life-story narration and dialogue approach. In-depth interviews were conducted with 38 HIV-positive participants sampled from a cohort of 1194 HIV-positive patients recruited from December 2017 to June 2018. Participants were selected based on whether they had been linked to care or not within 3 months of positive HIV diagnosis. Interviews were thematically analysed using a general inductive approach. Of the 38 participants, 22 (58%) linked to care within three months of HIV-positive diagnosis. Factors that facilitated or inhibited linkage-to-care were found at individual, family, community, as well as health systems levels. Enablers included a positive HIV testing experience, and assistance from the fieldwork team. Support from family, and friends, as well as prior community-based education about HIV and ART were also noted. Individual factors such as acceptance of HIV status, previous exposure to PLHIV, and fear of HIV progressing, were identified. Barriers to linkage included, denial of HIV status, dislike of taking pills, and preference for alternative medicine. Negative experiences with counselling and health systems inefficiency were also noted as barriers. Perceived stigma and socio-economic factors, such as lack of food or money to visit the clinic were other barriers. Community-based and health system-level interventions would need to focus on clinic readiness in providing patients with necessary and effective health services such as proper and adequate counselling. This could increase the number of patients who link to care. Finally, interventions to improve linkage-to-care should consider a holistic approach, including training healthcare providers, community outreach and the provision of psychological, social, and financial support.

Understanding the effects of universal test and treat on longitudinal HIV care outcomes among South African youth: a retrospective cohort study.

INTRODUCTION: Little is known about the effects of universal test and treat (UTT) policies on HIV care outcomes among youth living with HIV (YLHIV). Moreover, there is a paucity of information regarding when YLHIV are most susceptible to disengagement from care under the newest treatment guidelines. The longitudinal HIV care continuum is an underutilized tool that can provide a holistic understanding of population-level HIV care trajectories and be used to compare treatment outcomes across groups. We aimed to explore effects of the UTT policy on longitudinal outcomes among South African YLHIV and identify temporally precise opportunities for re-engaging this priority population in the UTT era. METHODS: Using medical record data, we conducted a retrospective cohort study among youth aged 18-24 diagnosed with HIV from August 2015-December 2018 in nine health care facilities in South Africa. We used Fine and Gray sub-distribution proportional hazards models to characterize longitudinal care continuum outcomes in the population overall and stratified by treatment era of diagnosis. We estimated the proportion of individuals in each stage of the continuum over time and the restricted mean time spent in each stage in the first year following diagnosis. Sub-group estimates were compared using differences. RESULTS: A total of 420 YLHIV were included. By day 365 following diagnosis, just 23% of individuals had no 90-or-more-day lapse in care and were virally suppressed. Those diagnosed in the UTT era spent less time as ART-naïve (mean difference=-19.3 days; 95% CI: -27.7, -10.9) and more time virally suppressed (mean difference = 17.7; 95% CI: 1.0, 34.4) compared to those diagnosed pre-UTT. Most individuals who were diagnosed in the UTT era and experienced a 90-or-more-day lapse in care disengaged between diagnosis and linkage to care or ART initiation and viral suppression. CONCLUSIONS: Implementation of UTT yielded modest improvements in time spent on ART and virally suppressed among South African YLHIV- however, meeting UNAIDS' 95-95-95 targets remains a challenge. Retention in care and re-engagement interventions that can be implemented between diagnosis and linkage to care and between ART initiation and viral suppression (e.g., longitudinal counseling) may be particularly important to improving care outcomes among South African YLHIV in the UTT era.

Thetha Nami ngithethe nawe (Let's Talk): a stepped-wedge cluster randomised trial of social mobilisation by peer navigators into community-based sexual health and HIV care, including pre-exposure prophylaxis (PrEP), to reduce sexually transmissible HIV amongst young people in rural KwaZulu-Natal, South Africa.

BACKGROUND: Antiretroviral therapy (ART) through universal test and treat (UTT) and HIV pre-exposure prophylaxis (PrEP) substantially reduces HIV-related mortality and incidence. Effective ART based prevention has not translated into population-level impact in southern Africa due to sub-optimal coverage among youth. We aim to investigate the effectiveness, implementation and cost effectiveness of peer-led social mobilisation into decentralised integrated HIV and sexual reproductive health (SRH) services amongst adolescents and young adults in KwaZulu-Natal (KZN). METHODS: We are conducting a type 1a hybrid effectiveness/implementation study, with a cluster randomized stepped-wedge trial (SWT) to assess effectiveness and a realist process evaluation to assess implementation outcomes. The SWT will be conducted in 40 clusters in rural KZN over 45 months. Clusters will be randomly allocated to receive the intervention in period 1 (early) or period 2 (delayed). 1) Intervention arm: Resident peer navigators in each cluster will approach young men and women aged 15-30 years living in their cluster to conduct health, social and educational needs assessment and tailor psychosocial support and health promotion, peer mentorship, and facilitate referrals into nurse led mobile clinics that visit each cluster regularly to deliver integrated SRH and differentiated HIV prevention (HIV testing, UTT for those positive, and PrEP for those eligible and negative). Standard of Care is UTT and PrEP delivered to 15-30 year olds from control clusters through primary health clinics. There are 3 co-primary outcomes measured amongst cross sectional surveys of 15-30 year olds: 1) effectiveness of the intervention in reducing the prevalence of sexually transmissible HIV; 2) uptake of universal risk informed HIV prevention intervention; 3) cost of transmissible HIV infection averted. We will use a realist process evaluation to interrogate the extent to which the intervention components support demand, uptake, and retention in risk-differentiated biomedical HIV prevention. DISCUSSION: The findings of this trial will be used by policy makers to optimize delivery of universal differentiated HIV prevention, including HIV pre-exposure prophylaxis through peer-led mobilisation into community-based integrated adolescent and youth friendly HIV and sexual and reproductive health care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier-NCT05405582. Registered: 6th June 2022.

Healthcare provider perceptions on the implementation of the universal test-and-treat policy in South Africa: a qualitative inquiry.

BACKGROUND: South Africa had an estimated 7.5 million people living with HIV (PLHIV), accounting for approximately 20% of the 38.4 million PLHIV globally in 2021. In 2015, the World Health Organization recommended the universal test and treat (UTT) intervention which was implemented in South Africa in September 2016. Evidence shows that UTT implementation faces challenges in terms of human resources capacity or infrastructure. We aim to explore healthcare providers (HCPs)' perspectives on the implementation of the UTT strategy in uThukela District Municipality in KwaZulu-Natal province. METHODS: A qualitative study was conducted with one hundred and sixty-one (161) healthcare providers (HCPs) within 18 healthcare facilities in three subdistricts, comprising of Managers, Nurses, and Lay workers. HCPs were interviewed using an open ended-survey questions to explore their perceptions providing HIV care under the UTT strategy. All interviews were thematically analysed using both inductive and deductive approaches. RESULTS: Of the 161 participants (142 female and 19 male), 158 (98%) worked at the facility level, of which 82 (51%) were nurses, and 20 (12.5%) were managers (facility managers and PHC manager/supervisors). Despite a general acceptance of the UTT policy implementation, HCPs expressed challenges such as increased patient defaulter rates, increased work overload, caused by the increased number of service users, and physiological and psychological impacts. The surge in the workload under conditions of inadequate systems' capacity and human resources, gave rise to a greater burden on HCPs in this study. However, increased life expectancy, good quality of life, and immediate treatment initiation were identified as perceived positive outcomes of UTT on service users. Perceived influence of UTT on the health system included, increased number of patients initiated, decreased burden on the system, meeting the 90-90-90 targets, and financial aspects. CONCLUSION: Health system strengthening such as providing more systems' capacity for expected increase in workload, proper training and retraining of HCPs with new policies in the management of patient readiness for lifelong ART journey, and ensuring availability of medicines, may reduce strain on HCPs, thus improving the delivery of the comprehensive UTT services to PLHIV.

Comparable Pregnancy Outcomes for HIV-Uninfected and HIV-Infected Women on Antiretroviral Treatment in Kenya.

BACKGROUND: The impact of human immunodeficiency virus (HIV) on pregnancy outcomes for women on antiretroviral therapy (ART) in sub-Saharan Africa remains unclear. METHODS: Pregnant women in Kenya were enrolled in the second trimester and followed up to delivery. We estimated effects of treated HIV with 3 pregnancy outcomes: loss, premature birth, and low birth weight and factors associated with HIV-positive status. RESULTS: Of 2113 participants, 311 (15%) were HIV infected and on ART. Ninety-one of 1762 (5%) experienced a pregnancy loss, 169/1725 (10%) a premature birth (<37 weeks), and 74/1317 (6%) had a low-birth-weight newborn (<2500 g). There was no evidence of associations between treated HIV infection and pregnancy loss (adjusted relative risk [aRR], 1.19; 95% confidence interval [CI], .65-2.16; P = .57), prematurity (aRR, 1.09; 95% CI, .70-1.70; P = .69), and low birth weight (aRR, 1.36; 95% CI, .77-2.40; P = .27). Factors associated with an HIV-positive status included older age, food insecurity, lower education level, higher parity, lower gestation at first antenatal clinic, anemia, and syphilis. Women who were overweight or underweight were less likely to be HIV infected compared to those with normal weight. CONCLUSIONS: Currently treated HIV was not significantly associated with adverse pregnancy outcomes. HIV-infected women, however, had a higher prevalence of other factors associated with adverse pregnancy outcomes.

CD4+ T-Cell Count at Antiretroviral Therapy Initiation in the "Treat-All" Era in Rural South Africa: An Interrupted Time Series Analysis.

BACKGROUND: South Africa implemented universal test and treat (UTT) in September 2016 in an effort to encourage earlier initiation of antiretroviral therapy (ART). METHODS: We therefore conducted an interrupted time series (ITS) analysis to assess the impact of UTT on mean CD4 count at ART initiation among adults aged ≥16 years attending 17 public sector primary care clinics in rural South Africa, between July 2014 and March 2019. RESULTS: Among 20 599 individuals (69% women), CD4 counts were available for 74%. Mean CD4 at ART initiation increased from 317.1 cells/µL (95% confidence interval [CI], 308.6 to 325.6) 1 to 8 months prior to UTT to 421.0 cells/µL (95% CI, 413.0 to 429.0) 1 to 12 months after UTT, including an immediate increase of 124.2 cells/µL (95% CI, 102.2 to 146.1). However, mean CD4 count subsequently fell to 389.5 cells/µL (95% CI, 381.8 to 397.1) 13 to 30 months after UTT but remained above pre-UTT levels. Men initiated ART at lower CD4 counts than women (-118.2 cells/µL, 95% CI, -125.5 to -111.0) throughout the study. CONCLUSIONS: Although UTT led to an immediate increase in CD4 count at ART initiation in this rural community, the long-term effects were modest. More efforts are needed to increase initiation of ART early in those living with human immunodeficiency virus, particularly men.

Developing sero-diagnostic tests to facilitate Plasmodium vivax Serological Test-and-Treat approaches: modeling the balance between public health impact and overtreatment.

BACKGROUND: Eliminating Plasmodium vivax will require targeting the hidden liver-stage reservoir of hypnozoites. This necessitates new interventions balancing the benefit of reducing vivax transmission against the risk of over-treating some individuals with drugs which may induce haemolysis. By measuring antibodies to a panel of vivax antigens, a strategy of serological-testing-and-treatment (PvSeroTAT) can identify individuals with recent blood-stage infections who are likely to carry hypnozoites and target them for radical cure. This provides a potential solution to selectively treat the vivax reservoir with 8-aminoquinolines. METHODS: PvSeroTAT can identify likely hypnozoite carriers with ~80% sensitivity and specificity. Diagnostic test sensitivities and specificities ranging 50-100% were incorporated into a mathematical model of vivax transmission to explore how they affect the risks and benefits of different PvSeroTAT strategies involving hypnozoiticidal regimens. Risk was measured as the rate of overtreatment and benefit as reduction of community-level vivax transmission. RESULTS: Across a wide range of combinations of diagnostic sensitivity and specificity, PvSeroTAT was substantially more effective than bloodstage mass screen and treat strategies and only marginally less effective than mass drug administration. The key test characteristic determining of the benefit of PvSeroTAT strategies is diagnostic sensitivity, with higher values leading to more hypnozoite carriers effectively treated and greater reductions in vivax transmission. The key determinant of risk is diagnostic specificity: higher specificity ensures that a lower proportion of uninfected individuals are unnecessarily treated with primaquine. These relationships are maintained in both moderate and low transmission settings (qPCR prevalence 10% and 2%). Increased treatment efficacy and adherence can partially compensate for lower test performance. Multiple rounds of PvSeroTAT with a lower performing test may lead to similar or higher reductions in vivax transmission than fewer rounds with a higher performing test, albeit with higher rate of overtreatment. CONCLUSIONS: At current performance, PvSeroTAT is predicted to be a safe and efficacious option for targeting the hypnozoite reservoir towards vivax elimination. P. vivax sero-diagnostic tests should aim for both high performance and ease of use in the field. The target product profiles informing such development should thus reflect the trade-offs between impact, overtreatment, and ease of programmatic implementation.

Early HIV treatment and survival over six years of observation in the ANRS 12249 Treatment as Prevention Trial.

OBJECTIVES: Population-based universal test and treat (UTT) trials have shown an impact on population-level virological suppression. We followed the ANRS 12249 TasP trial population for 6 years to determine whether the intervention had longer-term survival benefits. METHODS: The TasP trial was a cluster-randomized trial in South Africa from 2012 to 2016. All households were offered 6-monthly home-based HIV testing. Immediate antiretroviral therapy (ART) was offered through trial clinics to all people living with HIV (PLHIV) in intervention clusters and according to national guidelines in control clusters. After the trial, individuals attending the trial clinics were transferred to the public ART programme. Deaths were ascertained through annual demographic surveillance. Random-effects Poisson regression was used to estimate the effect of trial arm on mortality among (i) all PLHIV; (ii) PLHIV aware of their status and not on ART at trial entry; and (iii) PHLIV who started ART during the trial. RESULTS: Mortality rates among PLHIV were 9.3/1000 and 10.4/1000 person-years in the control and intervention arms, respectively. There was no evidence that the intervention decreased mortality among all PLHIV [adjusted rate ratio (aRR) = 1.10, 95% confidence interval (CI) = 0.85-1.43, p = 0.46] or among PLHIV who were aware of their status but not on ART. Among individuals who initiated ART, the intervention decreased mortality during the trial (aRR = 0.49, 95% CI = 0.28-0.85, p = 0.01), but not after the trial ended. CONCLUSIONS: The 'treat all' strategy reduced mortality among individuals who started ART but not among all PLHIV. To achieve maximum benefit of immediate ART, barriers to ART uptake and retention in care need to be addressed.

Point-of-care hepatitis C testing and treatment strategy for people attending harm reduction and addiction centres for hepatitis C elimination.

According to WHO goals, the elimination of Hepatitis C Virus (HCV) by 2030 requires enhancing and simplifying HCV testing. Our aim was to create a model to assess and compare different strategies for HCV testing, linkage to care and treatment among people who access harm reduction centres (HRC) and Addiction Centres in Catalonia. A decision tree model was designed to evaluate two strategies: Hepatitis C Point-of-care (POC) "test and treat", at the community versus standard-of-care (SOC), in which HCV testing was performed at community and therapy at the hospital. Both strategies were assessed separately in HRCs (6,878 users) and Addiction Centres (13,778 users). with a time horizon of 18 months. Healthcare outcomes were HCV testing, linkage to care, treatment outcomes and reinfection rate. HCV testing was performed in 3,178 (46%) of the HRC users. Compared with SOC, POC increased access to treatment by 57% (63% vs. 6%). SVR rates were 64% in POC vs. 23% in SOC. Reinfection rates were 21% with POC compared to 24% with SOC. With POC, losses to follow-up were reduced by 41%. In the Addiction Centres, 12,566 users (91%) were screened using the two strategies. Compared to the SOC, POC increased access to treatment and linkage to care by 19% along with SVR at the same rate. Reinfection rates decreased by 6%. Thus, the implementation of a POC "test and treat" strategy at HRCs and Addiction Centres has shown to be an effective public health strategy to help eliminating HCV in accordance with WHO goal.

Challenges with adherence to the 'test, treat, and track' malaria case management guideline among prescribers in Ghana.

BACKGROUND: Despite several efforts at addressing the barriers to adherence to the WHO-supported test, treat and track (T3) malaria case management guideline in Ghana, adherence remains a challenge. This study explored the challenges of prescribers regarding adherence to the T3 guideline. METHODS: This was an explorative study using key informant interviews amongst prescribers comprising medical doctors, physician assistants, nurses and a health extension worker from 16 health facilities in six districts in Ghana. The data was analysed using Nvivo 10 and organized into thematic areas. RESULTS: Prescribers lauded the guideline on testing and treatment as it ensures the quality of malaria case management, but irregular supply of malaria rapid diagnostic test kits (RDT), mistrust of laboratory tests, and the reluctance of prescribers to change from presumptive treatment were key barriers to testing. Patients with malaria test negative results if not treated, revisiting the facility with severe malaria, the experience of prescribers, lack of regular training and supervision for old and new staff and the inability of prescribers to investigate non-malaria fever hindered adherence to results-based treatment. CONCLUSION: As malaria remains a significant cause of morbidity and mortality in Ghana, this study provides insights on gaps in adherence to the testing and treatment of malaria. While the diagnostic capacity for malaria case management is a challenge, the lack of training resulting in the inability of some prescribers to investigate non-malaria fever hinders adherence to the malaria case management guideline. Therefore, there is a need to train new prescribers, laboratory personnel, and other staff involved in malaria diagnosis and treatment on the malaria case management guideline before they assume duty. Equipping laboratory personnel and prescribers with the knowledge to investigate non-malaria fevers could improve adherence to the guideline for improved patient care.