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Simplified drug regimens may improve retention in care for persons with chronic diseases. In April 2013, South Africa adopted a once-daily single-pill human immunodeficiency virus (HIV) treatment regimen as the standard of care, replacing a multiple-pill regimen. Because the regimens had similar biological efficacy, the shift to single-pill therapy offered a real-world test of the impact of simplified drug-delivery mechanisms on patient behavior. Using a quasi-experimental regression discontinuity design, we assessed retention in care among patients starting HIV treatment just before and just after the guideline change. The study included 4,484 patients starting treatment at a large public sector clinic in Johannesburg, South Africa. The share of patients prescribed a single-pill regimen increased by over 40 percentage points between March and April 2013. Initiating treatment after the policy change was associated with 11.7–percentage-points' higher retention at 12 months (95% confidence interval: −2.2, 29.4). Findings were robust to different measures of retention, different bandwidths, and different statistical models. Patients starting treatment early in HIV infection—a key population in the test-and-treat era—experienced the greatest improvements in retention from single-pill regimens. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

South African guidelines recommend repeat viral load testing within 6 months when human immunodeficiency virus (HIV) viral loads exceed 1,000 copies/mL. We assessed whether South African facilities follow viral load monitoring guidelines and whether guidelines improve HIV-related outcomes, using a regression discontinuity design in a national HIV cohort of 174,574 patients (2013–2015). We assessed whether patients with viral loads just above versus just below 1,000 copies/mL were more likely to receive repeat testing in 6 months, and we compared differences in clinic transfers, retention, and viral suppression. The majority (67%) of patients with viral loads of >1,000 copies/mL did not receive repeat testing within 6 months, and these patients were 8.0% (95% confidence interval (CI): 6.2, 9.7) more likely to receive repeat testing compared with ≤1,000 copies/mL. Eligibility for repeat testing (>1,000 copies/mL) was associated with greater 12-month retention (risk difference = 2.9%, 95% CI: 0.6, 5.2) and combined suppression and retention (risk difference = 5.8%, 95% CI: 3.0, 8.6). Patients with viral loads of >1,000 copies/mL who actually received repeat testing were 85.2% more likely to be both retained and virally suppressed at 12 months (95% CI: 35.9, 100.0). Viral load monitoring might improve patient outcomes, but most patients with elevated viral loads do not receive monitoring within recommended timelines. [ABSTRACT FROM AUTHOR]

Many countries have expanded insurance programmes in an effort to achieve universal health coverage (UHC). We assess a complementary path toward financial risk protection: increased access to technologies that improve health and reduce the risk of large health expenditures. Malawi has provided free HIV treatment since 2004 with significant US Government support. We investigate the impact of treatment access on medical spending, capacity to pay and catastrophic health expenditures at the population level, exploiting the phased rollout of HIV treatment in a difference-in-differences design. We find that increased access to HIV treatment generated a 10% decline in medical spending for urban households, a 7% increase in capacity to pay for rural households and a 3-percentage point decrease in the likelihood of catastrophic health expenditure among urban households. These risk protection benefits are comparable to that found from broad-based insurance coverage in other contexts. Our findings show that targeted treatment programmes that provide free care for high burden causes of death can provide substantial financial risk protection against catastrophic health expenditure, while moving developing nations toward UHC. [ABSTRACT FROM AUTHOR]

Tenofovir is less toxic than other nucleoside reverse-transcriptase inhibitors used in antiretroviral therapy (ART) and may improve retention of human immunodeficiency virus (HIV)–infected patients on ART. We assessed the impact of national guideline changes in South Africa (2010) and Zambia (2007) recommending tenofovir for first-line ART. We applied regression discontinuity in a prospective cohort study of 52,294 HIV-infected adults initiating first-line ART within 12 months (±12 months) of each guideline change. We compared outcomes in patients presenting just before and after the guideline changes using local linear regression and estimated intention-to-treat effects on initiation of tenofovir, retention in care, and other treatment outcomes at 24 months. We assessed complier causal effects among patients starting tenofovir. The new guidelines increased the percentages of patients initiating tenofovir in South Africa (risk difference (RD) = 81 percentage points, 95% confidence interval (CI): 73, 89) and Zambia (RD = 42 percentage points, 95% CI: 38, 45). With the guideline change, the percentage of single-drug substitutions decreased substantially in South Africa (RD = −15 percentage points, 95% CI: −18, −12). Starting tenofovir also reduced attrition in Zambia (intent-to-treat RD = −1.8% (95% CI: −3.5, −0.1); complier relative risk = 0.74) but not in South Africa (RD = −0.9% (95% CI: −5.9, 4.1); complier relative risk = 0.94). These results highlight the importance of reducing side effects for increasing retention in care, as well as the differences in population impact of policies with heterogeneous treatment effects implemented in different contexts. [ABSTRACT FROM AUTHOR]

Estimation of causal effects from observational data is a primary goal of epidemiology. The use of multiple methods with different assumptions relating to exchangeability improves causal inference by demonstrating robustness across assumptions. We estimated the effect of antiretroviral therapy (ART) on mortality in rural KwaZulu-Natal, South Africa, from 2007 to 2011, using 2 methods with substantially different assumptions: the regression discontinuity design (RDD) and inverse-probability–weighted (IPW) marginal structural models (MSMs). The RDD analysis took advantage of a CD4-cell-count–based threshold for ART initiation (200 cells/μL). The 2 methods yielded consistent but nonidentical results for the effect of immediate initiation of ART (RDD intention-to-treat hazard ratio (HR) = 0.66, 95% confidence interval (CI): 0.35, 1.26; RDD complier average causal effect HR = 0.56, 95% CI: 0.41, 0.77; IPW MSM HR = 0.49, 95% CI: 0.42, 0.58). Although RDD and IPW MSM estimates have distinct identifying assumptions, strengths, and limitations in terms of internal and external validity, results in this application were similar. The differences in modeling approaches and the external validity of each method may explain the minor differences in effect estimates. The overall consistency of the results lends support for causal inference about the effect of ART on mortality from these data. [ABSTRACT FROM AUTHOR]

Background. The South African national HIV program has increased antiretroviral therapy (ART) coverage over the last decade, supported by policy changes allowing for earlier ART initiation. However, many patients still enter care with advanced (<200 cells/µL) and very advanced (<100 cells/µL) HIV disease. We assessed disease progression at entry to care using nationwide laboratory data. Methods. We constructed a national HIV cohort using laboratory records containing HIV RNA loads and CD4 counts from 2004 to 2016 to determine entry into care. We estimated numbers and proportions of adults with the first CD4 count <100 cells/ µL or 100-199 cells/µL. We calculated relative risks of presenting with advanced disease associated with male sex. Results. 8.04 million first CD4 results were identified. From 2005 to 2011, the proportion of patients entering into care with CD4 count <200 cells/µL declined from 46.8% to 35.6%. From 2011 onward, the proportion of patients entering ART with advanced HIV disease has remained relatively unchanged. In 2016, we estimated that of 654 868 patients entering care, 32.9% had advanced HIV disease, and 16.8% had very advanced HIV disease. Men were almost twice as likely as women (23.1% vs 12.6% ) to enter care with very advanced HIV disease. Conclusions. The proportion of patients presenting with advanced HIV disease in South Africa remains consistently high despite ART scale-up, representing a large and avoidable burden of morbidity. Early HIV diagnosis, rapid linkage to ART and approaches to attract men into early ART initiation should be prioritized. [ABSTRACT FROM AUTHOR]

Background: Unlike other west European countries, there is a long-term trend of rising alcohol consumption and mortality in England. Whether drinking will rise or fall during the current recession is widely debated. We examined how the recession affected alcohol use in adults in England using individual-level data. Methods: We analysed a nationally representative sample of non-institutionalized white persons aged 20–60 years from seven waves of the Health Survey for England, 2004–2010 (n = 36 525), to assess trends in alcohol use and frequency before, during and after the recession and in association with unemployment, correcting for possible changes in sample composition and socio-demographic confounders. The primary analysis compared 2006/7 with 2008/9, following the official onset of the UK recession in early 2008. Results: During England’s recession, there was a significant decrease in frequent drinking defined as drinking four or more days in the past week (27.1% in 2006 to 23.9% in 2009, P < 0.001), the number of units of alcohol imbibed on the heaviest drinking day (P < 0.01) and the number of days that individuals reported drinking over the past seven days (P < 0.01). However, among current drinkers who were unemployed there was a significantly elevated risk of binge drinking in 2009 and 2010 (odds ratio = 1.64, 95% confidence interval: 1.22–2.19, P = 0.001) that was not previously observed in 2004–2008 (1.03, 0.76–1.41; test for effect heterogeneity: P = 0.036). Conclusions: England’s recession was associated with less hazardous drinking among the population overall, but with rises in binge drinking among a smaller high-risk group of unemployed drinkers. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to assess changes in alcohol use in the USA during the Great Recession. Methods: Drinking participation, drinking frequency, drinking intensity, total alcohol consumption and frequency of binge drinking were assessed in a nationally representative sample of 2,050,431 US women and men aged 18 and older, interviewed between 2006 and 2010. Results: The prevalence of any alcohol use significantly declined during the economic recession, from 52.0% in 2006-2007 to 51.6% in 2008-2009 (P<0.05), corresponding to 880,000 fewer drinkers (95% confidence interval [CI] 140,000 to 1.6 million). There was an increase, however, in the prevalence of frequent binging, from 4.8% in 2006-2007 to 5.1% in 2008-2009 (P<0.01), corresponding to 770,000 more frequent bingers (95% CI 390,000 to 1.1 million). Non-Black, unmarried men under 30 years, who recently became unemployed, were at highest risk for frequent binging. Conclusion: During the Great Recession there was an increase in abstention from alcohol and a rise in frequent binging. [ABSTRACT FROM AUTHOR]