Long-term neurocognitive, psychosocial, and physical outcomes after prenatal exposure to radiotherapy: a multicentre cohort study of the International Network on Cancer, Infertility, and Pregnancy.

BACKGROUND: The main data available on the safety of radiation during pregnancy originate from animal studies and from studies of survivors of atomic or nuclear disasters. The effect of radiotherapy to treat maternal cancer on fetal development is uncertain. This report presents a unique cohort and aims to determine the long-term neurocognitive, psychosocial and physical outcomes of offspring of mothers treated with radiotherapy during pregnancy. METHODS: In this international, multicentre, mixed retrospective-prospective cohort study, we recruited participants between Aug 5, 2006, and Aug 24, 2023, aged between 1·5 and 46 years, at three referral centres in Belgium, the Netherlands, and the USA. Participants were eligible if they were born from mothers treated with radiotherapy during pregnancy. Fetal radiation doses were obtained from medical records and participants were followed up at predefined ages (1·5, 3, 6, 9, 12, 15, and 18 years) and 5-yearly in adulthood, based on age at enrolment, using a neurocognitive test battery (measuring intelligence, attention, and memory), parent-reported executive function and psychosocial questionnaires, and a medical assessment. Results were compared with test-specific normative data. Linear regression models investigated associations between radiotherapy factors (fetal radiation dose, gestational age at the start and end of radiotherapy, and radiotherapy duration) and outcomes. FINDINGS: 68 maternal cases of radiotherapy during pregnancy were registered by the three participating centres, of which 61 resulted in a livebirth and were therefore eligible to participate in the child follow-up study. After excluding those who did not give consent, 43 participants born from 42 mothers treated with radiotherapy during pregnancy were included in the study (median age at first assessment 3 years [IQR 2-11]; median age at last assessment 12 years [9-18]; median number of assessments two [1-4]). 18 (42%) of the included participants were female and 25 (58%) male, and 37 (86%) were of White ethnicity. Mean neurocognitive outcomes of the entire cohort were within normal ranges. No associations were found with fetal radiation dose or timing of radiotherapy during pregnancy. Six (16%) of 38 participants with neurocognitive outcomes scored lower than one SD on at least one neurocognitive outcome, three (7%) reported chronic medical conditions (spasmophilia, spastic diplegia, and IgG deficiency), and three (7%) were diagnosed with attention-deficit hyperactivity disorder (of whom two scored lower on attention). Of ten (23%) participants with lower neurocognitive score(s), a chronic medical condition, or attention-deficit hyperactivity disorder, eight were born preterm. The remaining 33 (77%) participants showed no neurocognitive, psychosocial, or chronic physical problems. INTERPRETATION: We show on average normal neurocognitive, psychosocial, and physical outcomes after prenatal exposure to radiotherapy. Differences in outcomes could not be explained by exposure to radiotherapy during pregnancy. These results suggest that extra-abdomino-pelvic radiotherapy exposure during pregnancy in general does not adversely affect outcomes of liveborn children. Further research with a larger sample is necessary to confirm these findings. FUNDING: Kom Op Tegen Kanker, KWF Kankerbestrijding, Stichting Tegen Kanker, Research Foundation Flanders.

m-PIMA™ HIV1/2 VL: A suitable tool for HIV-1 and HIV-2 viral load quantification in West Africa.

Point-of-Care for HIV viral RNA quantification seems to be a complementary strategy to the existing conventional systems. This study evaluated the performance of the m-PIMA™ HIV1/2 Viral Load for the quantification of both HIV-1 and HIV-2 RNA viral load. A total of 555 HIV-1 and 90 HIV-2 samples previously tested by Abbott RealTime HIV-1 (Abbott, Chicago, USA) and Generic HIV-2® Charge virale (Biocentric, France) were tested using the m-PIMA™ HIV1/2 Viral Load at the HIV National Reference lab in Senegal. For HIV-1, Pearson correlation and Bland-Altman plots showed a coefficient r = 0.97 and a bias of -0.11 log10 copies/ml (95% confidence interval [CI]: -0.086 to -0.133 log10 copies/ml) for the m-PIMA™ HIV1/2 Viral Load, respectively. Sensitivity and specificity at 3 log10 copies/ml (threshold of virological failure) were 93.6% (95%[CI]: 91.5% to 95.6%) and 99.1% (95%[CI]: 98.3% to 99.9%), respectively. For HIV-2, a correlation of r = 0.95 was also noted with a bias of - 0.229 log10 copies/ml (95%[CI]: -0.161 to -0.297 log10 copies/ml). Sensitivity and specificity at 3 log10 copies/ml were 97.6% (95%[CI]: 94.3% to 100%) and 93.9% (95%[CI]: 88.9% to 98.8%), respectively. These results confirmed that m-PIMA™ HIV1/2 VL could be a good alternative for HIV-1 and HIV-2 viral load testing in decentralized settings in Senegal.

Validation of the point-of-care (POC) technologies Xpert HIV-1 Qual and m-PIMA HIV 1/2 detect for early diagnosis of HIV-1 and HIV-2 in Senegal.

Introduction: early infant diagnosis (EID) is crucial in the prevention of mother to child transmission (PMTCT) of human immunodeficiency virus (HIV) and is an essential component for the elimination of HIV. EID can be strengthened in resource-limited countries by the introduction and the roll out of real-time polymerase chain reaction (PCR) technologies via point-of-care (POC) devices which improves treatment in remote areas and reduces turnaround time for clinicians and patients to receive results and linkage to care. The objective of this study was to evaluate the performance of Xpert® HIV-1 Qual Assay (Cepheid) and m-PIMA™ HIV 1/2 Detect (ABBOTT) for EID of HIV-1 and HIV-2. Methods: the performance of the Xpert® HIV-1 qual device was evaluated with 192 samples including 100 dried blood spot (DBS) samples from the National Reference Laboratory biobank (71 negative and 29 positive samples) and an additional 92 whole blood samples collected from infants from neonatal departments. These infants from seven treatment centers in the Dakar region were born to mothers infected with HIV-1 (n=91), HIV-2 (n= 8) or HIV-1/2 (n=1). The m-PIMA™ HIV 1/2 detect assay was evaluated on whole blood samples (n=100) with 92 HIV-1 samples and 8 HIV-2 samples from children born to HIV-infected mothers. The Cobas AmpliPreP/Cobas TaqMan (CAP/CTM) platform from Roche Diagnostic Laboratories was used as a reference for HIV-1 diagnosis and the Generic HIV-2 Viral Load Assay (Biocentric) was used as a reference for HIV-2 diagnosis. Performance was evaluated by calculating sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and Cohen's kappa coefficient. Results: for HIV-1 detection on GeneXpert and m-PIMA, no discordance was found on the samples tested, i.e. a sensitivity of 100% (95% CI: 93.9-100%), a specificity of 100% (95% CI: 97.5-100%), a positive predictive value (PPV) of 100% (95% CI: 93.9-100%) and a negative predictive value (NPV) of 100% (95% CI: 97.5-100%). Agreement with Cobas AmpliPrep/Cobas TaqMan (CAP/CTM) was 100% with a Kappa coefficient of 1 (p<0.001, 95% CI) for both techniques. Similarly, the comparison between m-PIMA and generic biocentric for the detection of HIV-2 on the 8 samples tested showed perfect agreement. Conclusion: these results confirm the excellent performance of the Xpert® HIV-1 qual and m-PIMA™ HIV1/2 detect tests for the detection of HIV-1 and HIV-2 and encourage the extension of POC tests to improve access to EID in Senegal.

Performance of Xpert HIV-1 viral load test in Senegal: a country of high circulation of CRF02_AG.

Introduction: the introduction of the point-of-care in HIV-1 viral load quantification appears to be a complementary strategy to the existing conventional system of the acceleration plan for the achievement of the three 90s in Senegal. The objective of this study was to evaluate the performance of the Xpert® HIV-1 viral load in the context of circulation of non-B, non-C subtypes. Methods: two hundred samples, were tested on Xpert® HIV-1 Viral Load using 1 ml of plasma in comparison to 600 µl on Abbott Real-time HIV-1 assay. The difference between viral load values was considered significant for Dlog <0.5 log copies/ml. Results: a good correlation (r=0.985) was noted and confirmed using passing-bablok regression (slope 1.048; 95% CI: 1.036 to 1.069) for 188 samples with samples. A mean difference of 0.0075 log10 copies/ml for a 95% confidence interval (CI) of 0.002 log10 copies/ml to 0.013 log10 copies/ml was obtained. Sensitivity and specificity were respectively 93.6% and 93.5% at the threshold of 1.6 log10 copies/ml and 100% and 99% at the threshold of 3.0 log10 copies/ml. Conclusion: these results show that Xpert® HIV-1 Viral Load has excellent performance. In Senegal, and can be used for HIV viral load monitoring.

Pushing the boundaries. Concurrent Hodgkin lymphoma and breast cancer treatment with preservation of pregnancy: A case report.

Background: Breast cancer and hematological cancers are the most commonly diagnosed malignancies during pregnancy. This case report is the first to describe the ultimate challenge to preserve a pregnancy while the expectant mother is diagnosed and treated simultaneously for two concurrent primary malignancies, a stage IIA Hodgkin lymphoma and pT2N0(Sn) breast cancer. Clinical case: A 36-year-old pregnant primigravida underwent a routine non-invasive prenatal test at 14 weeks and 4 days of gestation. Genome-wide sequencing was used and revealed an aberrant DNA/chromosome copy number profile among which a strong 2p-gain, possibly related to a maternal malignancy. Physical examination showed an enlarged cervical lymph node and ultrasound guided biopsy confirmed the diagnosis of a nodular sclerosing classical Hodgkin lymphoma subsequently staged as an early stage, unfavorable (IIA) Hodgkin lymphoma. Whole body magnetic resonance imaging for further staging also indicated a suspicious nodule in the right breast. Further investigation resulted in the concurrent diagnosis of a pT2N0(Sn) invasive ductal adenocarcinoma. Patient underwent a mastectomy with sentinel lymph node biopsy at 15 weeks and 5 days of gestation, followed by 4-weekly chemotherapy administration, consisting of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). Pregnancy went further relatively uncomplicated and fetal assessment was reassuring during pregnancy. Due to fever of unknown origin and preterm labor, a cesarean section was performed on a gestational age of 35 weeks and 4 days. Oncological treatment was completed after delivery with involved-field radiation therapy for the Hodgkin lymphoma. Completion of systemic treatment for breast cancer consisted of docetaxel/cyclophosphamide chemotherapy, and anti-hormonal treatment in the form of ovarian function suppression and letrozole. Conclusion: Here we show for the first time that two concurrent primary malignancies can be treated successfully during pregnancy with respect to maternal and fetal chances. Motivated modifications of breast cancer treatment (mastectomy instead of lumpectomy, AVBD instead of epirubicin-cyclophosphamide chemotherapy), allowed treatment of both cancers during pregnancy. Final treatment was administered after delivery.

Longitudinal analysis of client appointment adherence under Universal Test and Treat strategy: A stepped-wedge trial.

OBJECTIVES: Universal Test and Treat (UTT) strategies are being adopted across sub-Saharan Africa based on clinical benefits to morbidity and mortality and to attain targets of the Joint United Nations Programme on HIV/AIDS (UNAIDS). Universal Test and Treat is expected to change the client population at clinics, due to more asymptomatic HIV clients initiating antiretroviral therapy (ART). We assessed the impact of UTT on client appointment adherence at 14 government-managed health facilities in Eswatini's public sector health system. METHODS: We assessed the impact of UTT on client adherence to appointment schedules from 2014 to 2017 in a stepped-wedge trial. Repeated measures analysis was used to assess adherence to each scheduled appointment (primary definition: presenting for care within 7 days after the scheduled appointment), adjusting for time, age, sex, stage, marital status, ART status and facility. RESULTS: Among 3354 clients (62.1% female; 57.4% < 35 years), a median (interquartile range) of 10 (6-15) appointments were scheduled during follow-up. In a multivariable-adjusted model, appointment adherence was significantly greater in clients who were female [odds ratio (OR) = 1.38, 95% confidence interval (CI): 1.25-1.52], older (e.g. 40 to < 50 years vs. < 20 years; OR = 1.45, 95% CI: 1.00-2.09), married (OR = 1.31, 95% CI: 1.19-1.44), had lower WHO stage at study enrolment (1-2 vs. 3-4: OR = 1.26, 95% CI: 1.13-1.41), and were currently on ART (OR = 3.55, 95% CI: 2.62-4.82). However, UTT strategy was not significantly associated with client adherence to scheduled appointments (OR = 1.02, 95% CI: 0.72-1.45). CONCLUSIONS: Despite transitioning to UTT, there was no change in visit adherence, a reassuring finding given the large volume of clients currently being initiated at earlier stages of HIV.

The Impact of Immediate Initiation of Antiretroviral Therapy on Patients' Healthcare Expenditures: A Stepped-Wedge Randomized Trial in Eswatini.

Immediate initiation of antiretroviral therapy (ART) for all people living with HIV has important health benefits but implications for the economic aspects of patients' lives are still largely unknown. This stepped-wedge cluster-randomized controlled trial aimed to determine the causal impact of immediate ART initiation on patients' healthcare expenditures in Eswatini. Fourteen healthcare facilities were randomly assigned to transition at one of seven time points from the standard of care (ART eligibility below a CD4 count threshold) to the immediate ART for all intervention (EAAA). 2261 patients living with HIV were interviewed over the study period to capture their past-year out-of-pocket healthcare expenditures. In mixed-effects regression models, we found a 49% decrease (RR 0.51, 95% CI 0.36, 0.72, p < 0.001) in past-year total healthcare expenditures in the EAAA group compared to the standard of care, and a 98% (RR 0.02, 95% CI 0.00, 0.02, p < 0.001) decrease in spending on private and traditional healthcare. Despite a higher frequency of HIV care visits for newly initiated ART patients, immediate ART initiation appears to have lowered patients' healthcare expenditures because they sought less care from alternative healthcare providers. This study adds an important economic argument to the World Health Organization's recommendation to abolish CD4-count-based eligibility thresholds for ART.

RESUMEN: El inicio inmediato de la terapia antirretroviral (TAR) para todas las personas que viven con VIH tiene importantes beneficios para la salud, pero aún se desconocen las implicaciones en el aspecto económico. Este ensayo controlado aleatorizado por clústers (CRT por sus siglas en inglés) por grupos en distintas etapas pretende determinar el impacto del inicio inmediato de la TAR en los gastos sanitarios de los pacientes en Eswatini. Catorce centros sanitarios fueron asignados aleatoriamente a la transición en uno de los siete periodos de la asistencia estándar (elegibilidad para la TAR en niveles definidos de recuento de CD4) a la intervención de TAR inmediato para todos (EAAA). Se entrevistó a 2.261 pacientes con VIH a lo largo del estudio para conocer sus gastos sanitarios del año anterior. Según los modelos de regresión de efectos mixtos, se observó un descenso del 49% (RR: 0,51; IC del 95%: 0,36, 0,72; p<0,001) en el gasto sanitario total del año anterior en el grupo de la EAAA, y un descenso del 98% (RR 0,02; IC del 95%: 0,00, 0,02; p<0,001) en el gasto en asistencia sanitaria privada y tradicional. A pesar de una mayor frecuencia de visitas deatención de VIH para los pacientes que recién comenzaron laTAR, la aplicación inmediata de laTAR redujo los gastos sanitarios de los pacientes dado que buscaron menos atención de proveedores de asistencia sanitaria alternativos. Este estudio añade un importante argumento económico a la recomendación de la Organización Mundial de la Salud de abolir las restricciones de elegibilidad para la terapia antirretroviral basados en el recuento de CD4.

Early access to antiretroviral therapy versus standard of care among HIV-positive participants in Eswatini in the public health sector: the MaxART stepped-wedge randomized controlled trial.

INTRODUCTION: The WHO recommends antiretroviral treatment (ART) for all HIV-positive patients regardless of CD4 count or disease stage, referred to as "Early Access to ART for All" (EAAA). The health systems effects of EAAA implementation are unknown. This trial was implemented in a government-managed public health system with the aim to examine the "real world" impact of EAAA on care retention and viral suppression. METHODS: In this stepped-wedge randomized controlled trial, 14 public sector health facilities in Eswatini were paired and randomly assigned to stepwise transition from standard of care (SoC) to EAAA. ART-naïve participants ≥18 years who were not pregnant or breastfeeding were eligible for enrolment. We used Cox proportional hazard models with censoring at clinic transition to estimate the effects of EAAA on retention in care and retention and viral suppression combined. RESULTS: Between September 2014 and August 2017, 3405 participants were enrolled. In SoC and EAAA respectively, 12-month HIV care retention rates were 80% (95% CI: 77 to 83) and 86% (95% CI: 83 to 88). The 12-month combined retention and viral suppression endpoint rates were 44% (95% CI: 40 to 48) under SoC compared to 80% (95% CI: 77 to 83) under EAAA. EAAA increased both retention (HR: 1·60, 95% CI: 1·15 to 2·21, p = 0.005) and retention and viral suppression combined (HR: 4.88, 95% CI: 2.96 to 8.05, p < 0.001). We also identified significant gaps in current health systems ability to provide viral load (VL) monitoring with 80% participants in SoC and 66% in EAAA having a missing VL at last contact. CONCLUSIONS: The observed improvement in retention in care and on the combined retention and viral suppression provides an important co-benefit of EAAA to HIV-positive adults themselves, at least in the short term. Our results from this "real world" health systems trial strongly support EAAA for Eswatini and countries with similar HIV epidemics and health systems. VL monitoring needs to be scaled up for appropriate care management.

A stepped-wedge randomised trial on the impact of early ART initiation on HIV-patients' economic outcomes in Eswatini.

Background: Since 2015, the World Health Organisation (WHO) recommends immediate initiation of antiretroviral therapy (ART) for all HIV-positive patients. Epidemiological evidence points to important health benefits of immediate ART initiation; however, the policy's impact on the economic aspects of patients' lives remains unknown. Methods: We conducted a stepped-wedge cluster-randomised controlled trial in Eswatini to determine the causal impact of immediate ART initiation on patients' individual- and household-level economic outcomes. Fourteen healthcare facilities were non-randomly matched into pairs and then randomly allocated to transition from the standard of care (ART eligibility at CD4 counts of <350 cells/mm3 until September 2016 and <500 cells/mm3 thereafter) to the 'Early Initiation of ART for All' (EAAA) intervention at one of seven timepoints. Patients, healthcare personnel, and outcome assessors remained unblinded. Data were collected via standardised paper-based surveys with HIV-positive adults who were neither pregnant nor breastfeeding. Outcomes were patients' time use, employment status, household expenditures, and household living standards. Results: A total sample of 3019 participants were interviewed over the duration of the study. The mean number of participants approached at each facility per time step varied from 4 to 112 participants. Using mixed-effects negative binomial regressions accounting for time trends and clustering at the level of the healthcare facility, we found no significant difference between study arms for any economic outcome. Specifically, the EAAA intervention had no significant effect on non-resting time use (RR = 1.00 [CI: 0.96, 1.05, p=0.93]) or income-generating time use (RR = 0.94, [CI: 0.73,1.20, p=0.61]). Employment and household expenditures decreased slightly but not significantly in the EAAA group, with risk ratios of 0.93 [CI: 0.82, 1.04, p=0.21] and 0.92 [CI: 0.79, 1.06, p=0.26], respectively. We also found no significant treatment effect on households' asset ownership and living standards (RR = 0.96, [CI 0.92, 1.00, p=0.253]). Lastly, there was no evidence of heterogeneity in effect estimates by patients' sex, age, education, timing of HIV diagnosis and ART initiation. Conclusions: Our findings do not provide evidence that should discourage further investments into scaling up immediate ART for all HIV patients. Funding: Funded by the Dutch Postcode Lottery in the Netherlands, Alexander von Humboldt-Stiftung (Humboldt-Stiftung), the Embassy of the Kingdom of the Netherlands in South Africa/Mozambique, British Columbia Centre of Excellence in Canada, Doctors Without Borders (MSF USA), National Center for Advancing Translational Sciences of the National Institutes of Health and Joachim Herz Foundation. Clinical trial number: NCT02909218 and NCT03789448.

Human immunodeficiency virus (HIV) is an incurable virus that attacks the immune system and affects around 39 million people worldwide. Once diagnosed, HIV can be treated with antiretroviral therapy (ART) to limit its effects and stop it spreading to other people. HIV rates vary across the world, but the African country of Eswatini has the highest prevalence with more than one in four (27%) people classed as HIV-positive. Until 2015, people living with HIV were typically only treated with ART once their immune system weakened. Recent studies found that starting treatment earlier enhances the positive effects of ART. This caused the World Health Organization (WHO) to change their guidelines and advise people living with HIV to begin ART as soon as they are diagnosed. While antiretroviral drugs are usually provided to patients free of charge, accessing care can be expensive for patients because of high transport costs or lost time from income-generating activities. This means starting treatment earlier and, thus, having more frequent healthcare visits, may result in a greater cost to the patient. The economic impact of this change is unclear, and for patients living in poverty, these added costs can affect their decision on whether to continue treatment. Steinert et al. interviewed 3,019 HIV-patients from 14 health facilities in Eswatini who began treatment with ART either immediately after diagnosis or after their immune system became suppressed. Patients were asked about their time spent being active to generate income, employment status, monthly household expenditures, and household living standards. On average, beginning ART earlier appears to have had no large negative effects on the economic wellbeing of patients. The same results were found for patient groups defined by sex, education, age, and time spent taking ART. These findings suggest that starting ART for HIV as soon as possible offers medical benefits and seems to have no large economic consequences for patients in the short term, even for poorer communities. This adds weight to the WHO advice on HIV treatment and supports the need to continue to deliver effective treatments to countries like Eswatini that have a high rate of HIV infection.

Getting to 90-90-90: Experiences from the MaxART Early Access to ART for All (EAAA) Trial in Eswatini.

PURPOSE OF REVIEW: The MaxART Consortium-led by the Eswatini Ministry of Health-implemented multiple interventions between 2012 and 2017 to achieve UNAIDS 90-90-90 targets. We summarize key findings from community outreach strategies in support of the first 90 goal, and from the Early Access to ART for All (EAAA) trial on the implementation of a "Treat All" strategy to achieve the second and third 90 goals within a government-managed public health system. RECENT FINDINGS: The MaxART Consortium demonstrated that "Fast Track," a problem-solving approach, was effective at increasing testing coverage in the community. Compared with baseline data at 3 months prior to the start of the Fast Track, there was a 273% proportional increase in HIV tests conducted among adolescent males, adolescent females, and adult men, and 722% over baseline for adolescent males. The MaxART EAAA trial further showed that implementation of the Treat All policy was associated with significant two-fold shorter time from enrollment into care to ART initiation than under the standard CD4+ cell threshold-based treatment guidelines. Finally, through the MaxART trial, Eswatini was able to identify areas for further investment, including addressing the system-side barriers to routine viral load monitoring, and designing and implementing innovative community-based approaches to reach individuals who were not more routinely accessing HIV testing and counseling services. As low- and middle-income countries adopt the Treat All approach in their national HIV care and treatment guidelines, further implementation science research is needed to understand and address the system-level barriers to achieving the benefits of Treat All for HIV-infected individuals and those at risk.

Impact of immediate initiation of antiretroviral therapy on HIV patient satisfaction.

OBJECTIVES: Immediate ART (or early access to ART for all, EAAA) is becoming a national policy in many countries in sub-Saharan Africa. It is plausible that the switch from delayed to immediate ART could either increase or decrease patient satisfaction with treatment. A decrease in patient satisfaction would likely have detrimental consequences for long-term retention and adherence, in addition to the value lost because of the worsening patient experience itself. We conducted a pragmatic stepped-wedge cluster-randomized controlled trial (SW-cRCT) to determine the causal impact of immediate treatment for HIV on patient satisfaction. DESIGN: This seven-step SW-cRCT took place in 14 public-sector health facilities in Eswatini's Hhohho region, from September 2014 to August 2017. METHODS: During each step of the trial, we randomly selected days for data collection at each study facility. During these days, a random sample of HIV patients were selected for outcome assessment. In total, 2629 patients provided data on their overall patient satisfaction and satisfaction with the following four domains of the patient experience using a five-point Likert scale: wait time, consultation time, involvement in treatment decisions, and respectful treatment. Higher values on the Likert scale indicated lower patient satisfaction. We analyzed the data using a multilevel ordered logistic regression model with individuals at the first level and health facilities at the second (cluster) level. RESULTS: The proportional odds ratio (OR) comparing EAAA to control was 0.91 (95% CI 0.66-1.25) for overall patient satisfaction. For the specific domains of the patient experience, the ORs describing the impact of EAAA on satisfaction were 1.04 (95% CI 0.61-1.78) for wait time, 0.90 (95% CI 0.62-1.31) for involvement in treatment decisions, 0.86 (95% CI 0.61-1.20) for consultation time, and 1.35 (95% CI 0.93-1.96) for respectful treatment. These results were robust across a wide range of sensitivity analyses. Over time - and independent of EAAA - we observed a worsening trend for both overall patient satisfaction and satisfaction in the four domains of the patient experience we measured. CONCLUSION: Our findings support the policy change from delayed to immediate ART in sub-Saharan Africa. Immediate (versus delayed) ART in public-sector health facilities in Eswatini had no effect on either overall patient satisfaction or satisfaction with four specific domains of the patient experience. At the same time, we observed a strong secular trend of decreasing patient satisfaction in both the intervention and the control arm of the trial. Further implementation research should identify approaches to ensure high patient satisfaction as ART programs grow and mature.

'This is mine, this is for me': preexposure prophylaxis as a source of resilience among women in Eswatini.

OBJECTIVE: To understand the relationship between HIV preexposure prophylaxis (PrEP) and resilience among Emaswati women. DESIGN: A qualitative study using semistructured in-depth interviews. METHODS: We interviewed 24 women who recently initiated PrEP at one of six public-sector primary-care clinics participating in a government demonstration project for PrEP for the general population, as well as 30 PrEP stakeholders from HIV policy, implementation and donor sectors. RESULTS: PrEP clients and stakeholders described an environment marked by high HIV risk. In this context, clients felt PrEP enhanced their resilience through feelings of protection, control over HIV acquisition, choice in relation to when to take PrEP, sexual pleasure and relief from the fear and consequences of HIV infection. Those in serodiscordant relationships described improved partner communication and a shared sense of responsibility for HIV prevention. Both PrEP clients and stakeholders asserted that PrEP marketing and communication should be Emaswati-led and community-owned. CONCLUSION: PrEP helps women in Eswatini envision longer, healthier and more fulfilled lives. PrEP enhances resilience through several pathways, including self-efficacy, choice, control over HIV infection and relief from the fear of HIV infection. Social marketing and information campaigns should not only focus on PrEP as an HIV-prevention method but also emphasize how PrEP has expanded choice, enhanced control and facilitated sexual enjoyment among PrEP clients.

Preference for injectable over oral HIV pre-exposure prophylaxis in public-sector primary-care clinics in Swaziland.

: Long-acting injectable (LAI) HIV pre-exposure prophylaxis (PrEP) may mitigate adherence challenges reported by young women in Southern Africa. We assessed preferences for PrEP in public-sector, primary care clinics in Swaziland. Among surveyed respondents, 75% (95% confidence interval = 65-83%) stated preference for LAI over oral PrEP; with no differences by sex, age, or sexual behavior (all P > 0.05). Notably, over 70% (95% confidence interval 58-82%) with current use of oral PrEP also stated preference for LAI PrEP.

Identification of misdiagnosed HIV clients in an Early Access to ART for All implementation study in Swaziland.

INTRODUCTION: Rapid diagnostic testing has made HIV diagnosis and subsequent treatment more accessible. However, multiple factors, including improper implementation of testing strategies and clerical errors, have been reported to lead to HIV misdiagnosis. The World Health Organization has recommended HIV retesting prior to antiretroviral therapy (ART) initiation which has become pertinent with scaling up of Early Access to ART for All (EAAA). In this analysis, misdiagnosed clients are identified from a subgroup of clients enrolled in EAAA implementation study in Swaziland. METHODS: The subgroup to assess misdiagnosis was identified from enrolled EAAA study clients, who had an undetectable viral load prior to ART initiation between September 1, 2014 and May 31, 2016. One hundred and five of 2533 (4%) clients had an undetectable viral load prior to initiation to ART (pre-ART). The HIV status of clients was confirmed using the Determine HIV 1/2 and Uni-Gold HIV 1/2 rapid tests performed serially as recommended by the national testing algorithm. The status of clients on ART was additionally confirmed by fourth-generation HIV Ag/Ab combo tests, Architect and Genscreen Ultra. RESULTS: Fourteen of the 105 (13%) clients were false positive (HIV negative) on confirmation testing, of whom five (36%) were still in pre-ART care, while nine (64%) were in ART care. Overall, proportion of false positive was 0.6% (14/2533). The false-positive clients had a median CD4 of 791 cells/ml (interquartile range (IQR): 628, 967) compared to 549 cells/ml (IQR: 387, 791) for true positives (HIV positive) (p = 0.0081) and were nearly 20 years older (p = 0.0008). CONCLUSIONS: Overall 0.6% of all enrolled EAAA clients were misdiagnosed, and 64% of misdiagnosed clients were initiated on ART. With adoption of EAAA guidelines by national governments, ART initiation regardless of immunological criteria, strengthening of proficiency testing and adoption of retesting prior to ART initiation would allow identification of misdiagnosed clients and further reduce potential of initiating misdiagnosed clients on ART.

Impact of early initiation versus national standard of care of antiretroviral therapy in Swaziland's public sector health system: study protocol for a stepped-wedge randomized trial.

BACKGROUND: There is robust clinical evidence to support offering early access to antiretroviral treatment (ART) to all HIV-positive individuals, irrespective of disease stage, to both improve patient health outcomes and reduce HIV incidence. However, as the global treatment guidelines shift to meet this evidence, it is still largely unknown if early access to ART for all (also referred to as "treatment as prevention" or "universal test and treat") is a feasible intervention in the resource-limited countries where this approach could have the biggest impact on the course of the HIV epidemics. The MaxART Early Access to ART for All (EAAA) implementation study was designed to determine the feasibility, acceptability, clinical outcomes, affordability, and scalability of offering early antiretroviral treatment to all HIV-positive individuals in Swaziland's public sector health system. METHODS: This is a three-year stepped-wedge randomized design with open enrollment for all adults aged 18 years and older across 14 government-managed health facilities in Swaziland's Hhohho Region. Primary endpoints are retention and viral suppression. Secondary endpoints include ART initiation, adherence, drug resistance, tuberculosis, HIV disease progression, patient satisfaction, and cost per patient per year. Sites are grouped to transition two at a time from the control (standard of care) to intervention (EAAA) stage at each four-month step. This design will result in approximately one half of the total observation time to accrue in the intervention arm and the other half in the control arm. Our estimated enrolment number, which is supported by conservative power calculations, is 4501 patients over the course of the 36-month study period. A multidisciplinary, mixed-methods approach will be adopted to supplement the randomized controlled trial and meet the study aims. Additional study components include implementation science, social science, economic evaluation, and predictive HIV incidence modeling. DISCUSSION: A stepped-wedge randomized design is a causally strong and robust approach to determine if providing antiretroviral treatment for all HIV-positive individuals is a feasible intervention in a resource-limited, public sector health system. We expect our study results to contribute to health policy decisions related to the HIV response in Swaziland and other countries in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02909218 . Registered on 10 July 2016.