Recruiting and retaining community-based participants in a COVID-19 longitudinal cohort and social networks study: lessons from Victoria, Australia.

BACKGROUND: Longitudinal studies are critical to informing evolving responses to COVID-19 but can be hampered by attrition bias, which undermines their reliability for guiding policy and practice. We describe recruitment and retention in the Optimise Study, a longitudinal cohort and social networks study that aimed to inform public health and policy responses to COVID-19. METHODS: Optimise recruited adults residing in Victoria, Australia September 01 2020-September 30 2021. High-frequency follow-up data collection included nominating social networks for study participation and completing a follow-up survey and four follow-up diaries each month, plus additional surveys if they tested positive for COVID-19 or were a close contact. This study compared number recruited to a-priori targets as of September 302,021, retention as of December 31 2021, comparing participants retained and not retained, and follow-up survey and diary completion October 2020-December 2021. Retained participants completed a follow-up survey or diary in each of the final three-months of their follow-up time. Attrition was defined by the number of participants not retained, divided by the number who completed a baseline survey by September 302,021. Survey completion was calculated as the proportion of follow-up surveys or diaries sent to participants that were completed between October 2020-December 2021. RESULTS: At September 302,021, 663 participants were recruited and at December 312,021, 563 were retained giving an overall attrition of 15% (n = 100/663). Among the 563 retained, survey completion was 90% (n = 19,354/21,524) for follow-up diaries and 89% (n = 4936/5560) for monthly follow-up surveys. Compared to participants not retained, those retained were older (t-test, p <  0.001), and more likely to be female (χ2, p = 0.001), and tertiary educated (χ2, p = 0.018). CONCLUSION: High levels of study retention and survey completion demonstrate a willingness to participate in a complex, longitudinal cohort study with high participant burden during a global pandemic. We believe comprehensive follow-up strategies, frequent dissemination of study findings to participants, and unique data collection systems have contributed to high levels of study retention.

WHO method for estimating congenital syphilis to inform surveillance and service provision, Paraguay.

Problem: In Paraguay, incomplete surveillance data resulted in the burden of congenital syphilis being underestimated, which, in turn, led to missed opportunities for infant diagnosis and treatment. Approach: The prevalence of congenital syphilis, as defined by the World Health Organization (WHO), was estimated for Paraguay using the WHO congenital syphilis estimation tool. This tool was also used to monitor progress towards the elimination of mother-to-child transmission of syphilis. Local setting: The burden of syphilis in Paraguay has historically been high: its prevalence in pregnant women was estimated to be 3% in 2018. Relevant changes: The incidence rate of congenital syphilis estimated using the WHO tool was around nine times the reported prevalence. Subsequently, Paraguay: (i) provided training to improve diagnosis and case reporting; (ii) strengthened information systems for case monitoring and reporting; and (iii) procured additional rapid dual HIV-syphilis and rapid plasma reagin tests to increase syphilis testing capacity. In addition, the Ministry of Health prepared a new national plan for eliminating mother-to-child transmission of syphilis, with clear monitoring milestones. Lessons learnt: Health-care providers' reporting and surveillance procedures for congenital syphilis may not adequately reflect national and international case definitions. Use of the WHO congenital syphilis estimation tool in Paraguay drew attention to congenital syphilis as a national public health problem and highlighted the importance of comprehensive national surveillance systems and accurate data. Ongoing use of the WHO tool can track progress towards the elimination of mother-to-child transmission of syphilis by helping improve syphilis service coverage and national surveillance.

Methylene Blue/Collagen Mixture for CT-Guided Presurgical Lung Nodule Marking: High Efficacy and Safety.

PURPOSE: To assess outcomes of computed tomography (CT)-guided methylene blue/collagen marking of preoperative lung nodules before video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracic surgery (RATS). MATERIALS AND METHODS: A retrospective cohort study assessing 25 methylene blue/collagen solution CT-guided lung nodule localization procedures on 26 nodules in 25 patients was performed. The procedures were performed by a fellowship-trained radiologist 1-2 hours before scheduled surgery under local anesthesia. Approximately 4-6 ml of methylene blue/collagen solution was injected in a perinodular location under CT guidance with a 19-gauge trocar needle and along the track to the visceral pleural surface. Post-procedural CT images confirmed appropriate lung nodule location marking. RESULTS: Perinodular CT-guided trocar needle placement was achieved in all marking procedures (n = 26/26). Increased consolidation near the target nodule was also demonstrated in all patients on the post-procedural localized CT scans. One patient with moderate emphysema developed a small to moderate-sized pneumothorax (∼20%-30%), and an 8-Fr thoracentesis catheter was placed under CT guidance before surgery. There was no bleeding or hemoptysis in any patient. Methylene blue/collagen solution was readily visible by the thoracic surgeon in association with all target nodules. One patient required conversion to open procedure due to the proximal portion of the right lower lobe pulmonary artery segmental branch. Of the 26 identified nodules, pathology specimens confirmed the adequacy of nodule resection in all cases. CONCLUSIONS: Preoperative CT-guided methylene blue/collagen solution injection offers a safe and highly effective technique for marking subpleural lung nodules undergoing VATS or RATS.

Long-Term Treatment Outcomes of Patients Infected With Hepatitis C Virus: A Systematic Review and Meta-analysis of the Survival Benefit of Achieving a Sustained Virological Response.

BACKGROUND: Achievement of a sustained virologic response (SVR) after treatment for Hepatitis C infection is associated with improved outcomes. This meta-analysis aimed to determine the impact of SVR on long-term mortality risk compared with nonresponders in a range of populations. METHODS: An electronic search identified all studies assessing all-cause mortality in SVR and non-SVR patients. Eligible articles were stratified into general, cirrhotic, and populations coinfected with human immunodeficiency virus. The adjusted hazard ratio (95% confidence interval [CI]) for mortality in patients achieving SVR vs non-SVR, and pooled estimates for the 5-year mortality in each group were calculated. RESULTS: 31 studies (n = 33 360) were identified as suitable for inclusion. Median follow-up time was 5.4 years (interquartile range, 4.9-7.5) across all studies. The adjusted hazard ratio of mortality for patients achieving SVR vs non-SVR was 0.50 (95% CI, .37-.67) in the general population, 0.26 (95% CI, .18-.74) in the cirrhotic group, and 0.21 (.10-.45) in the coinfected group. The pooled 5-year mortality rates were significantly lower for patients achieving SVR compared with non-SVR in all 3 populations. CONCLUSIONS: The results suggest that there is a significant survival benefit of achieving an SVR compared with unsuccessful treatment in a range of populations infected with hepatitis C virus.

Same-visit hepatitis C testing and treatment to accelerate cure among people who inject drugs (the QuickStart Study): a cluster randomised cross-over trial protocol.

INTRODUCTION: Despite universal access to government-funded direct-acting antivirals (DAAs) in 2016, the rate of hepatitis C treatment uptake in Australia has declined substantially. Most hepatitis C is related to injecting drug use; reducing the hepatitis C burden among people who inject drugs (PWID) is, therefore, paramount to reach hepatitis C elimination targets. Increasing DAA uptake by PWID is important for interrupting transmission and reducing incidence, as well as reducing morbidity and mortality and improving quality of life of PWID and meeting Australia's hepatitis C elimination targets. METHODS AND ANALYSIS: A cluster randomised cross-over trial will be conducted with three intervention arms and a control arm. Arm A will receive rapid hepatitis C virus (HCV) antibody testing; arm B will receive rapid HCV antibody and rapid RNA testing; arm C will receive rapid HCV antibody testing and same-day treatment initiation for HCV antibody-positive participants; the control arm will receive standard of care. The primary outcomes will be (a) the proportion of participants with HCV commencing treatment and (b) the proportion of participants with HCV achieving cure. Analyses will be conducted on an intention-to-treat basis with mixed-effects logistic regression models. ETHICS AND DISSEMINATION: The study has been approved by the Alfred Ethics Committee (number HREC/64731/Alfred-2020-217547). Each participant will provide written informed consent. Reportable adverse events will be reported to the reviewing ethics committee. The findings will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05016609. TRIAL PROGRESSION: The study commenced recruitment on 9 March 2022 and is expected to complete recruitment in December 2024.

Priority populations' experiences of isolation, quarantine and distancing for COVID-19: protocol for a longitudinal cohort study (Optimise Study).

INTRODUCTION: Longitudinal studies can provide timely and accurate information to evaluate and inform COVID-19 control and mitigation strategies and future pandemic preparedness. The Optimise Study is a multidisciplinary research platform established in the Australian state of Victoria in September 2020 to collect epidemiological, social, psychological and behavioural data from priority populations. It aims to understand changing public attitudes, behaviours and experiences of COVID-19 and inform epidemic modelling and support responsive government policy. METHODS AND ANALYSIS: This protocol paper describes the data collection procedures for the Optimise Study, an ongoing longitudinal cohort of ~1000 Victorian adults and their social networks. Participants are recruited using snowball sampling with a set of seeds and two waves of snowball recruitment. Seeds are purposively selected from priority groups, including recent COVID-19 cases and close contacts and people at heightened risk of infection and/or adverse outcomes of COVID-19 infection and/or public health measures. Participants complete a schedule of monthly quantitative surveys and daily diaries for up to 24 months, plus additional surveys annually for up to 48 months. Cohort participants are recruited for qualitative interviews at key time points to enable in-depth exploration of people's lived experiences. Separately, community representatives are invited to participate in community engagement groups, which review and interpret research findings to inform policy and practice recommendations. ETHICS AND DISSEMINATION: The Optimise longitudinal cohort and qualitative interviews are approved by the Alfred Hospital Human Research Ethics Committee (# 333/20). The Optimise Study CEG is approved by the La Trobe University Human Ethics Committee (# HEC20532). All participants provide informed verbal consent to enter the cohort, with additional consent provided prior to any of the sub studies. Study findings will be disseminated through public website (https://optimisecovid.com.au/study-findings/) and through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05323799.

Keeping kids in school: modelling school-based testing and quarantine strategies during the COVID-19 pandemic in Australia.

Background: In 2021, the Australian Government Department of Health commissioned a consortium of modelling groups to generate evidence assisting the transition from a goal of no community COVID-19 transmission to 'living with COVID-19', with adverse health and social consequences limited by vaccination and other measures. Due to the extended school closures over 2020-21, maximizing face-to-face teaching was a major objective during this transition. The consortium was tasked with informing school surveillance and contact management strategies to minimize infections and support this goal. Methods: Outcomes considered were infections and days of face-to-face teaching lost in the 45 days following an outbreak within an otherwise COVID-naïve school setting. A stochastic agent-based model of COVID-19 transmission was used to evaluate a 'test-to-stay' strategy using daily rapid antigen tests (RATs) for close contacts of a case for 7 days compared with home quarantine; and an asymptomatic surveillance strategy involving twice-weekly screening of all students and/or teachers using RATs. Findings: Test-to-stay had similar effectiveness for reducing school infections as extended home quarantine, without the associated days of face-to-face teaching lost. Asymptomatic screening was beneficial in reducing both infections and days of face-to-face teaching lost and was most beneficial when community prevalence was high. Interpretation: Use of RATs in school settings for surveillance and contact management can help to maximize face-to-face teaching and minimize outbreaks. This evidence supported the implementation of surveillance testing in schools in several Australian jurisdictions from January 2022.

Estimating the proportion of Victorians infected with COVID-19 during the Omicron BA.1 epidemic wave of January 2022 in Australia.

OBJECTIVE: To estimate the proportion of Victorians infected with COVID-19 in January 2022. METHODS: Between 11-19 February 2022 we conducted a nested cross-sectional survey on experiences of COVID-19 testing, symptoms, test outcome and barriers to testing during January 2022 in Victoria, Australia. Respondents were participants of the Optimise Study, a prospective cohort of adults considered at increased risk of COVID-19 or the unintended consequences of COVID-19-related interventions. RESULTS: Of the 577 participants, 78 (14%) reported testing positive to COVID-19, 240 (42%) did not test in January 2022 and 91 of those who did not test (38%) reported COVID-19-like symptoms. Using two different definitions of symptoms, we calculated symptomatic (27% and 39%) and asymptomatic (4% and 11%) test positivity. We extrapolated these positivity rates to participants who did not test and estimated 19-22% of respondents may have had COVID-19 infection in January 2022. CONCLUSION: The proportion of Victorians infected with COVID-19 in January 2022 was likely considerably higher than officially reported numbers. IMPLICATIONS FOR PUBLIC HEALTH: Our estimate is approximately double the COVID-19 case numbers obtained from official case reporting. This highlights a major limitation of diagnosis data that must be considered when preparing for future waves of infection.

I know what you did last summer: a cross-sectional study of personal COVID-19 risk reduction strategies used by Victorian adults, December 2021-January 2022.

OBJECTIVE: We describe COVID-19 risk reduction strategies adopted by Victorian adults during December 2021-January 2022, a period of high COVID-19 infection and limited government mandated public health measures. METHODS: In February 2022, participants of a Victorian-based cohort study (Optimise) completed a cross-sectional survey on risk reduction behaviours during December 2021-January 2022. Regression modelling estimated the association between risk reduction and demographics. RESULTS: A total of 556 participants were included (median age 47 years; 75% women; 82% in metropolitan Melbourne). Two-thirds (61%) adopted at least one risk reduction behaviour, with uptake highest among younger participants (18-34 years; adjusted relative risk (aRR): 1.20, 95% confidence interval [CI]: 1.01, 1.41) and those with a chronic health condition (aRR: 1.17, 95% CI: 1.02, 1.35). CONCLUSIONS: Participants adopted their own COVID-19 risk reduction strategies in a setting of limited government restrictions, with young people more likely to adopt a risk reduction strategy that did not limit social mobility. IMPLICATION FOR PUBLIC HEALTH: A public health response to COVID-19 that focusses on promoting personal risk reduction behaviours, as opposed to mandated restrictions, could be enhanced by disseminating information on and increasing availability of effective risk reduction strategies tailored to segments of the population.

Mathematical modelling of the mosquito Aedes polynesiensis in a heterogeneous environment.

BACKGROUND: The mosquito Aedes polynesiensis inhabits Pacific islands and territories and transmits arboviruses and parasites. In the context of rapid environmental change, understanding the effects of environmental heterogeneity on mosquitoes is crucial. METHODS: First, empirical field data and remote sensing data were combined to model spatial heterogeneity in the environmental suitability for Ae. polynesiensis. Second, a model of mosquito population dynamics was applied to predict mosquito distributions over a heterogeneous landscape assuming different dispersal behaviours. Motu Tautau, French Polynesia, was used as a case study of the utility of this methodological approach. Ae. polynesiensis use land crab Cardisoma carnifex burrows for oviposition in French Polynesia; environmental suitability was therefore quantified using C. carnifex burrow density. RESULTS: Micro-regions with large Ae. polynesiensis populations facilitated by high C. carnifex burrow density were accurately captured by our methodology. Preferential dispersal towards oviposition sites promoted larger population sizes than non-preferential dispersal but did not offer greater resilience to environmental change. Reduced environmental suitability for Ae. polynesiensis resulted in spatially non-linear effects upon the mosquito distribution. CONCLUSIONS: Environmental change has complex spatial effects upon mosquito populations. Mosquito control strategies must carefully balance spatial effects with net effects.

Intent to Be Vaccinated against COVID-19 in Victoria, Australia.

BACKGROUND: High vaccine uptake requires strong public support, acceptance, and willingness. METHODS: A longitudinal cohort study gathered survey data every four weeks between 1 October 2020 and 9 November 2021 in Victoria, Australia. Data were analysed for 686 participants aged 18 years and older. RESULTS: Vaccine intention in our cohort increased from 60% in October 2020 to 99% in November 2021. Vaccine intention increased in all demographics, but longitudinal trends in vaccine intention differed by age, employment as a healthcare worker, presence of children in the household, and highest qualification attained. Acceptance of vaccine mandates increased from 50% in October 2020 to 71% in November 2021. Acceptance of vaccine mandates increased in all age groups except 18-25 years; acceptance also varied by gender and highest qualification attained. The main reasons for not intending to be vaccinated included safety concerns, including blood clots, and vaccine efficacy. CONCLUSION: COVID-19 vaccination campaigns should be informed by understanding of the sociodemographic drivers of vaccine acceptance to enable socially and culturally relevant guidance and ensure equitable vaccine coverage. Vaccination policies should be applied judiciously to avoid polarisation.

The Joint United Nations Programme on HIV/AIDS 95-95-95 targets: worldwide clinical and cost benefits of generic manufacture.

BACKGROUND: The Joint United Nations Programme on HIV/AIDS aims for HIV testing, treatment and viral suppression rates to be 95%--95%--95% by 2025. Patented drug prices remain a barrier to HIV treatment. Generic alternatives are being produced and exported from countries without patent barriers at a fraction of the cost. METHODS: We collated export records of active pharmaceutical ingredient for HIV drugs to estimate the minimum costs of production. Using epidemiological data describing national HIV epidemics, we calculated the cost to treat 164 countries at 95%--95%-95%. Using weighted log-linear regression models, we estimated the mother-to-child transmissions (MTCTs), HIV-related deaths and new HIV infections preventable every year by increased treatment. FINDINGS: We estimated that TDF/3TC/DTG could be produced for $59 per person per year. At this price, the 164 countries in our analysis could be treated at 95%--95%--95% for $2 billion a year, preventing 66 308 MTCTs, 241 811 HIV-related deaths and 631 398 new HIV infections every year. In comparison, global expenditure on HIV pharmaceuticals in 2019 was $28 billion. INTERPRETATION: At $2 billion/year, the 164 countries in our analysis could be treated for the price of 4 weeks of current global sales. Global access to generic alternatives could reduce expenditure and improve clinical outcomes.

Estimation of benzathine penicillin G demand for congenital syphilis elimination with adoption of dual HIV/syphilis rapid diagnostic tests in eleven high burden countries.

BACKGROUND: WHO recommends use of rapid dual HIV/syphilis tests for screening pregnant women (PW) during antenatal care to prevent mother-to-child transmission. Scale-up of testing implies a need to accurately forecast and procure benzathine penicillin (BPG) to treat the additionally identified PW with syphilis. METHODS: Country-reported ANC coverage, PW syphilis screening and treatment coverage values in 2019 were scaled linearly to EMTCT targets by 2030 (constant increasing slope from 2019 figures to 95% in 2030) for 11 focus countries. Antenatal syphilis screening coverage was substituted with HIV screening coverage to estimate potential contribution of rapid dual HIV/syphilis tests in identifying additional PW with syphilis. BPG demand was calculated for 2019-2030 accordingly. RESULTS: The estimated demand for BPG (in 2.4 million unit vials) using current maternal syphilis prevalence and treatment coverage will increase from a baseline of 414,459 doses in 2019 to 683,067 doses (+65%) in 2021 assuming immediate replacement of single HIV test kits with rapid dual HIV/syphilis tests for these 11 countries. Continued scale up of syphilis screening and treatment coverage to reach elimination coverage of 95% will result in an estimated demand increase of 160%, (663,969 doses) from 2019 baseline for a total demand of 1,078,428 BPG doses by 2030. CONCLUSIONS: Demand for BPG will increase following adoption of rapid dual HIV/syphilis test kits due to increases in maternal diagnoses of syphilis. To eliminate congenital syphilis, MNCH clinical programs will need to synergize with disease surveillance programs to accurately forecast BPG demand with scale up of antenatal syphilis screening to ensure adequate treatment is available for pregnant women diagnosed with syphilis.

Most new HIV infections, vertical transmissions and AIDS-related deaths occur in lower-prevalence countries.

OBJECTIVES: The Joint United Nations Programme on HIV/AIDS (UNAIDS) targets aim to reduce new HIV infections below 500,000 per year by 2020. Despite targeted prevention programmes, total new infections remained in 2016 and 2017 at 1,800,000 cases. We have aimed to analyse data from 2017 and to compare HIV incidence, AIDS-related deaths and provision of antiretroviral therapy (ART) to adults, pregnant women and children living with HIV in lower- and higher-prevalence countries. Vertical or mother-to-child transmission (MTCT) and early infant diagnosis (EID) rates were also investigated. METHODS: UNAIDSinfo data use the Spectrum model to represent country-level HIV data. Countries with epidemics over 40,000 HIV cases were separated into higher prevalence (≥4.5%) and lower prevalence (<4.5%). Least squares linear regression, weighted by epidemic size and controlled for gross domestic product/capita, was used to compare HIV prevalence with estimated ART coverage in adults (≥15 years), children (0-14 years), pregnant women, and EID rates and MTCT rates. Data were then compared between higher- and lower-prevalence groups, including numbers of new HIV infections and AIDS-related deaths. RESULTS: Data were available for 56 countries. Twelve higher-prevalence countries accounted for 16.7 million and 44 lower-prevalence ones for 15.1 million people living with HIV, altogether making up 87.5% of the global estimate. Lower-prevalence countries had less ART coverage for adults, pregnant women and children, lower EID rates and higher AIDS-related death levels. There were more new HIV infections in adults and children in lower- than higher-prevalence countries. CONCLUSIONS: Most new HIV infections, MTCTs and AIDS-related deaths occurred in countries with an HIV prevalence rate below 4.5%. Many of these countries are not targeted by access programmes, such as the President' Emergency Plan for AIDS Relief. More intensive programmes of diagnosis and treatment are needed in these countries in the effort to reduce global new HIV infections below 500,000 per year by 2020.

Cost-effectiveness analysis of treatment timing considering the future entry of lower-cost generics for hepatitis C.

BACKGROUND: Cost-benefit analyses are crucial to inform treatment policies, particularly when the cost of patented drugs is very high. The cost of patented drugs is the limiting factor in hepatitis C treatment. However, hepatitis C drug costs are expected to fall following patent expiration, due to generic drug introduction. METHODS: An existing mathematical model by Shih et al was extended to consider lower-cost future generics in health economic models of hepatitis C. The model compared the cost-effectiveness of treating patients now with patented drugs vs postponing treatment until after patent expiration. RESULTS: For ledipasvir-sofosbuvir, this study finds that it is almost always more cost effective to treat hepatitis C with high-cost patented drugs immediately rather than waiting for patent expiry. For ledipasvir-sofosbuvir, a generic would need to enter the market at <16.40% of the patented price for delayed treatment to be cost effective. The further that patent expiry is in the future, the more cost effective delayed treatment becomes; however, uncertainty about generic pricing and market entry times are also higher if patent expiry is in the distant future. CONCLUSION: It is more cost effective to treat hepatitis C sooner rather than later, regardless of the stage of the disease, and despite the high cost of patented drugs. However, patented drugs are being produced globally for prices much lower than those seen in the UK. Therefore, negotiation of patented drug prices with pharmaceutical companies may be a crucial step in cost effective treatment of hepatitis C.

The impact of HIV prevalence, conflict, corruption, and GDP/capita on treatment cascades: data from 137 countries.

OBJECTIVE: In 2014, UNAIDS and partners set the 90-90-90 targets for the HIV treatment cascade. Multiple social, political and structural factors might influence progress towards these targets. We assessed how close countries and regions are to reaching these targets, and compared cascade outcomes with HIV prevalence, gross domestic product (GDP)/capita, conflict and corruption. METHODS: Country-level HIV cascade data on diagnosis, ART coverage and viral suppression, from 2010 to 2016 were extracted from national reports, published papers and the www.AIDSinfoOnline database, and analysed. Weighted least-squares regression was used to assess predictors of cascade achievement: region, HIV prevalence, GDP/capita, the 2016 Corruption Perceptions Index (CPI), which is an international ranking system, and the 2016 Global Peace Index (GPI), which ranks all countries based on three main categories: societal safety, militarisation and conflict. RESULTS: Data were available for diagnosis for 84 countries, ART coverage for 137 countries, and viral suppression for 94 countries. Regions with the lowest ART coverage were South-east Asia and Pacific (36%), Eastern Europe and Central Asia (17%), and Middle East and North Africa (13%). Lower HIV prevalence was associated with poorer cascade results. Countries with higher GDP/capita achieved higher ART coverage (P<0.001). Furthermore, countries with lower levels of peace and higher corruption had lower ART coverage (P<0.001). Countries with a GPI >2.5 all had ART coverage of <40%. CONCLUSION: Only one country has reached the UNAIDS 90-90-90 targets. International comparison remains difficult due to heterogeneous data reporting. Difficulty meeting UNAIDS targets is associated with lower GDP/capita, lower HIV prevalence, higher corruption and conflict levels.

Correction: Disparities in the Burden of HIV/AIDS in Canada.

[This corrects the article DOI: 10.1371/journal.pone.0047260.].

Higher risks of mother-to-child HIV transmission in countries with lower HIV prevalence: UNAIDS 2013 results for 32 countries with generalised epidemics.

OBJECTIVES: Diagnosis and treatment of HIV-infected mothers significantly lower rates of mother-to-child transmission (MTCT) of HIV. Early infant diagnosis (EID) is required to monitor success of prevention of MTCT (pMTCT) programmes. Our aim was to compare rates of MTCT, EID and pMTCT in countries with generalised epidemics. METHODS: The UNAIDSinfo database includes country-level information on epidemic size, prevalence of HIV infection, EID rates and pMTCT coverage. The AIDS Spectrum model was used to estimate the number of children infected with HIV in 2013, for 32 countries with generalised epidemics. Least squares linear regression, weighted by epidemic size and controlling for GDP/capita, was used to correlate national adult HIV prevalence with estimated MTCT rates. RESULTS: There were 32 countries with generalised epidemics included in the analysis (31 in Africa). Higher-prevalence countries (≥5%) had significantly lower rates of MTCT (P<0.01) than lower-prevalence countries (<5%). For 20 lower-prevalence countries (total 7.4 million HIV-infected people), there were 105,300 childhood (0-14 years) infections in 2013. In 12 higher-prevalence countries (total 17.1 million HIV-infected people), there were an estimated 107,500 childhood infections in 2013. Regression analysis suggests that if all countries achieved the same MTCT rate as Botswana (2.0%), childhood HIV infections could be cut by 88% (from 105,300 to 12,300 per year) in lower-prevalence countries, and by 82% (from 107,500 to 19,700 per year) in higher-prevalence countries. CONCLUSIONS: In this analysis of 32 countries with generalised HIV epidemics, 49.5% (105,500/213,000) of childhood HIV infections in 2013 were in lower-prevalence countries. Targeting of prevention of MTCT in lower-prevalence countries needs to be prioritised, despite challenges, to reduce the number of children infected.

Provider bias in the selection of non-nucleoside reverse transcriptase inhibitor and protease inhibitor-based highly active antiretroviral therapy and HIV treatment outcomes in observational studies.

OBJECTIVE: To compare the characteristics of patients prescribed non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI), and evaluate treatment outcomes in a setting in which nevirapine has been preferentially recommended since 1998. METHODS: A population-based analysis of antiretroviral-naive adults who started highly active antiretroviral therapy (HAART) between 1 August 1996 and 31 July 2000, and who were followed until 31 March 2002. We compared baseline characteristics, and evaluated virological responses and mortality. RESULTS: Overall, 439 patients (28.8%) started HAART with NNRTI (94.1% used nevirapine), 100 (6.6%) used a double PI, and 983 (64.6%) used a single PI-based regimen. Substantial differences were observed between the baseline clinical characteristics of these populations. In adjusted analyses, in comparison with single PI therapy, only the use of NNRTI was associated with more rapid HIV-RNA suppression [relative hazard (RH) 1.42; 95% confidence interval (CI) 1.22-1.65; P < 0.001]. A total of 204 deaths were identified in the study population [42 (9.6%) NNRTI; 11 (11%) double PI; 151 (15.4%) single PI, respectively]. In adjusted analysis, NNRTI (RH 1.01; 95% CI 0.71-1.45) and double PI-based HAART (RH 0.74; 95% CI 0.40-1.39) had similar mortality rates to the single PI reference category. CONCLUSION: NNRTI use was associated with more rapid virological suppression, whereas similar rates of rebound and mortality were found. Nevertheless, major baseline differences existed between patients prescribed the various initial regimens. As such, it is likely that similar selection factors may explain why our findings contrast with several non-randomized studies showing worse clinical outcomes of patients prescribed nevirapine.