Summary Background New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously ...recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. Methods We used several independent mathematical models in four settings—South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)—to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost effective if the cost per DALY averted was less than the country's 2012 per-head gross domestic product (GDP; South Africa: $8040; Zambia: $1425; India: $1489; Vietnam: $1407) and cost effective if the cost per DALY averted was less than three times the per-head GDP. Findings In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from $237 to $1691 per DALY averted compared with 2010 guidelines. In Zambia, expansion of eligibility to adults with a CD4 count threshold of 500 cells per μL ranged from improving health outcomes while reducing costs (ie, dominating the previous guidelines) to $749 per DALY averted. In both countries results were similar for expansion of eligibility to all HIV-positive adults, and when substantially expanded treatment coverage was assumed. Expansion of treatment coverage in the general population was also cost effective. In India, the cost for extending eligibility to all HIV-positive adults ranged from $131 to $241 per DALY averted, and in Vietnam extending eligibility to patients with CD4 counts of 500 cells per μL or less cost $290 per DALY averted. In concentrated epidemics, expanded access for key populations was also cost effective. Interpretation Our estimates suggest that earlier eligibility for antiretroviral therapy is very cost effective in low-income and middle-income settings, although these estimates should be revisited when more data become available. Scaling up antiretroviral therapy through earlier eligibility and expanded coverage should be considered alongside other high-priority health interventions competing for health budgets. Funding Bill & Melinda Gates Foundation, WHO.
Summary Background The post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these ...targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements. Methods 11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa. Models were calibrated with data on tuberculosis incidence and mortality in 2012. Representatives from national tuberculosis programmes and the advocacy community provided distinct country-specific intervention scenarios, which included screening for symptoms, active case finding, and preventive therapy. Findings Aggressive scale-up of any single intervention scenario could not achieve the post-2015 End TB Strategy targets in any country. However, the models projected that, in the South Africa national tuberculosis programme scenario, a combination of continuous isoniazid preventive therapy for individuals on antiretroviral therapy, expanded facility-based screening for symptoms of tuberculosis at health centres, and improved tuberculosis care could achieve a 55% reduction in incidence (range 31–62%) and a 72% reduction in mortality (range 64–82%) compared with 2015 levels. For India, and particularly for China, full scale-up of all interventions in tuberculosis-programme performance fell short of the 2025 targets, despite preventing a cumulative 3·4 million cases. The advocacy scenarios illustrated the high impact of detecting and treating latent tuberculosis. Interpretation Major reductions in tuberculosis burden seem possible with current interventions. However, additional interventions, adapted to country-specific tuberculosis epidemiology and health systems, are needed to reach the post-2015 End TB Strategy targets at country level. Funding Bill and Melinda Gates Foundation
Increased sexual risk behaviour and HIV prevalence have been reported in migrants compared with non-migrants in sub-Saharan Africa. We investigated the association of residential and migration ...patterns with sexual HIV risk behaviours and HIV prevalence in an open, general population cohort in rural KwaZulu-Natal, South Africa.
In a mainly rural demographic surveillance area in northern KwaZulu-Natal, South Africa, we collected longitudinal demographic, migration, sexual behaviour, and HIV status data through household surveillance twice per year and individual surveillance once per year. All resident household members and a sample of non-resident household members (stratified by sex and migration patterns) were eligible for participation. Participants reported sexual risk behaviours, including data for multiple, concurrent, and casual sexual partners and condom use, and gave a dried blood spot sample via fingerprick for HIV testing. We investigated population-level differences in sexual HIV risk behaviours and HIV prevalence with respect to migration indicators using logistic regression models.
Between Jan 1, 2005, and Dec 31, 2011, the total eligible population at each surveillance round ranged between 21 129 and 22 726 women (aged 17–49 years) and between 20 399 and 22 100 men (aged 17–54 years). The number of eligible residents in any round ranged from 24 395 to 26 664 and the number of eligible non-residents ranged from 17 002 to 18 891 between rounds. The stratified sample of non-residents included between 2350 and 3366 individuals each year. Sexual risk behaviours were significantly more common in non-residents than in residents for both men and women. Estimated differences in sexual risk behaviours, but not HIV prevalence, varied between the migration indicators: recent migration, mobility, and migration type. HIV prevalence was significantly increased in current residents with a recent history of migration compared with other residents in the study area in men (adjusted odds ratio 1·19, 95% CI 1·07–1·33) and in women (1·18, 1·10–1·26).
Local information about migrants and highly mobile individuals could help to target intervention strategies that are based on the identification of transmission hotspots.
Wellcome Trust.
Summary Background Mathematical models are widely used to simulate the effects of interventions to control HIV and to project future epidemiological trends and resource needs. We aimed to validate ...past model projections against data from a large household survey done in South Africa in 2012. Methods We compared ten model projections of HIV prevalence, HIV incidence, and antiretroviral therapy (ART) coverage for South Africa with estimates from national household survey data from 2012. Model projections for 2012 were made before the publication of the 2012 household survey. We compared adult (age 15–49 years) HIV prevalence in 2012, the change in prevalence between 2008 and 2012, and prevalence, incidence, and ART coverage by sex and by age groups between model projections and the 2012 household survey. Findings All models projected lower prevalence estimates for 2012 than the survey estimate (18·8%), with eight models' central projections being below the survey 95% CI (17·5–20·3). Eight models projected that HIV prevalence would remain unchanged (n=5) or decline (n=3) between 2008 and 2012, whereas prevalence estimates from the household surveys increased from 16·9% in 2008 to 18·8% in 2012 (difference 1·9, 95% CI −0·1 to 3·9). Model projections accurately predicted the 1·6 percentage point prevalence decline (95% CI −0·3 to 3·5) in young adults aged 15–24 years, and the 2·2 percentage point (0·5 to 3·9) increase in those aged 50 years and older. Models accurately represented the number of adults on ART in 2012; six of ten models were within the survey 95% CI of 1·54–2·12 million. However, the differential ART coverage between women and men was not fully captured; all model projections of the sex ratio of women to men on ART were lower than the survey estimate of 2·22 (95% CI 1·73–2·71). Interpretation Projections for overall declines in HIV epidemics during the ART era might have been optimistic. Future treatment and HIV prevention needs might be greater than previously forecasted. Additional data about service provision for HIV care could help inform more accurate projections. Funding Bill & Melinda Gates Foundation.
Antiretroviral therapy (ART) substantially decreases morbidity and mortality in people living with HIV. In this study, we describe population-level trends in the adult life expectancy and trends in ...the residual burden of HIV mortality after the roll-out of a public sector ART programme in KwaZulu-Natal, South Africa, one of the populations with the most severe HIV epidemics in the world.
Data come from the Africa Centre Demographic Information System (ACDIS), an observational community cohort study in the uMkhanyakude district in northern KwaZulu-Natal, South Africa. We used non-parametric survival analysis methods to estimate gains in the population-wide life expectancy at age 15 years since the introduction of ART, and the shortfall of the population-wide adult life expectancy compared with that of the HIV-negative population (ie, the life expectancy deficit). Life expectancy gains and deficits were further disaggregated by age and cause of death with demographic decomposition methods.
Covering the calendar years 2001 through to 2014, we obtained information on 93 903 adults who jointly contribute 535 42 8 person-years of observation to the analyses and 9992 deaths. Since the roll-out of ART in 2004, adult life expectancy increased by 15·2 years for men (95% CI 12·4-17·8) and 17·2 years for women (14·5-20·2). Reductions in pulmonary tuberculosis and HIV-related mortality account for 79·7% of the total life expectancy gains in men (8·4 adult life-years), and 90·7% in women (12·8 adult life-years). For men, 9·5% is the result of a decline in external injuries. By 2014, the life expectancy deficit had decreased to 1·2 years for men (-2·9 to 5·8) and to 5·3 years for women (2·6-7·8). In 2011-14, pulmonary tuberculosis and HIV were responsible for 84·9% of the life expectancy deficit in men and 80·8% in women.
The burden of HIV on adult mortality in this population is rapidly shrinking, but remains large for women, despite their better engagement with HIV-care services. Gains in adult life-years lived as well as the present life expectancy deficit are almost exclusively due to differences in mortality attributed to HIV and pulmonary tuberculosis.
Wellcome Trust, the Bill & Melinda Gates Foundation, and the National Institutes of Health.
With expanded access to antiretroviral therapy (ART) in sub-Saharan Africa, HIV mortality has decreased, yet life-years are still lost to AIDS. Strengthening of treatment programmes is a priority. We ...examined the state of an HIV care programme in Kenya and assessed interventions to improve the impact of ART programmes on population health.
We created an individual-based mathematical model to describe the HIV epidemic and the experiences of care among adults infected with HIV in Kenya. We calibrated the model to a longitudinal dataset from the Academic Model Providing Access To Healthcare (known as AMPATH) programme describing the routes into care, losses from care, and clinical outcomes. We simulated the cost and effect of interventions at different stages of HIV care, including improvements to diagnosis, linkage to care, retention and adherence of ART, immediate ART eligibility, and a universal test-and-treat strategy.
We estimate that, of people dying from AIDS between 2010 and 2030, most will have initiated treatment (61%), but many will never have been diagnosed (25%) or will have been diagnosed but never started ART (14%). Many interventions targeting a single stage of the health-care cascade were likely to be cost-effective, but any individual intervention averted only a small percentage of deaths because the effect is attenuated by other weaknesses in care. However, a combination of five interventions (including improved linkage, point-of-care CD4 testing, voluntary counselling and testing with point-of-care CD4, and outreach to improve retention in pre-ART care and on-ART) would have a much larger impact, averting 1·10 million disability-adjusted life-years (DALYs) and 25% of expected new infections and would probably be cost-effective (US$571 per DALY averted). This strategy would improve health more efficiently than a universal test-and-treat intervention if there were no accompanying improvements to care ($1760 per DALY averted).
When resources are limited, combinations of interventions to improve care should be prioritised over high-cost strategies such as universal test-and-treat strategy, especially if this is not accompanied by improvements to the care cascade. International guidance on ART should reflect alternative routes to programme strengthening and encourage country programmes to evaluate the costs and population-health impact in addition to the clinical benefits of immediate initiation.
Bill & Melinda Gates Foundation, United States Agency for International Development, National Institutes of Health.
Abstract Background England's National Chlamydia Screening Programme (NCSP) aims to control infection and reduce sequelae. Public Health England developed a novel monitoring indicator included in the ...Public Health Outcomes Framework, the diagnosed incidence rate (DIR), with a target of 2300 cases of chlamydia per 100 000 resident 15–24-year-old young people per year. We assessed the utility of DIR as a measure of performance at local authority level. Methods We used the NCSP 2012 dataset to derive coverage, positivity, population size, and DIR and linked the dataset to indices of multiple deprivation (IMD) 2010 scores. We used multivariate logistic regression to analyse the association between the DIR (local authorities categorised as achieved or did not achieve the target) and coverage, positivity, population size, IMD score, and proportion of tests done in a genitourinary medicine setting. Findings The dataset included 3 403 922 female residents and 3 516 609 male residents from 326 local authorities, two of which were excluded (one with missing values and one suppressed because of small numbers). The recommended DIR of 2300 per 100 000 was achieved by 72 (22%) of 324 local authorities, with those in the most deprived quintile being more likely to reach the target than those in the least deprived quintile (adjusted odds ratio AOR for women 25·83, 95% CI 8·70–76·68; men 6·83, 1·34–34·72). The proportion of tests done in a genitourinary medicine setting was negatively associated with attaining the recommended DIR (AOR 0·93, 95% CI 0·91–0·96). No clear associations with population size were seen. Interpretation Greater socioeconomic deprivation strongly influenced whether local authorities attained the recommended DIR. This finding could reflect increased disease burden rather than more appropriate targeting of testing. Consequently, use of the DIR to compare performance of local authorities is difficult. Local-authority-specific DIR targets that reflect local disease burden might be more effective than a single national target. Additionally, the results indicate that an increased proportion of tests done in a genitourinary medicine setting was associated with a reduced likelihood of reaching the DIR target, which suggests the need for more testing outside of this setting, particularly in the least deprived areas. Critical evaluation of local authority performance should be used to inform subsequent versions of the Public Health Outcomes Framework. Funding BD received a Medical Research Council Population Health Scientist Fellowship. JWE received funding from the Bill & Melinda Gates Foundation through a grant to the HIV Modelling Consortium.
Summary Background Cash-transfer programmes can improve the wellbeing of vulnerable children, but few studies have rigorously assessed their effectiveness in sub-Saharan Africa. We investigated the ...effects of unconditional cash transfers (UCTs) and conditional cash transfers (CCTs) on birth registration, vaccination uptake, and school attendance in children in Zimbabwe. Methods We did a matched, cluster-randomised controlled trial in ten sites in Manicaland, Zimbabwe. We divided each study site into three clusters. After a baseline survey between July, and September, 2009, clusters in each site were randomly assigned to UCT, CCT, or control, by drawing of lots from a hat. Eligible households contained children younger than 18 years and satisfied at least one other criteria: head of household was younger than 18 years; household cared for at least one orphan younger than 18 years, a disabled person, or an individual who was chronically ill; or household was in poorest wealth quintile. Between January, 2010, and January, 2011, households in UCT clusters collected payments every 2 months. Households in CCT clusters could receive the same amount but were monitored for compliance with several conditions related to child wellbeing. Eligible households in all clusters, including control clusters, had access to parenting skills classes and received maize seed and fertiliser in December, 2009, and August, 2010. Households and individuals delivering the intervention were not masked, but data analysts were. The primary endpoints were proportion of children younger than 5 years with a birth certificate, proportion younger than 5 years with up-to-date vaccinations, and proportion aged 6–12 years attending school at least 80% of the time. This trial is registered with ClinicalTrials.gov , number NCT00966849. Findings 1199 eligible households were allocated to the control group, 1525 to the UCT group, and 1319 to the CCT group. Compared with control clusters, the proportion of children aged 0–4 years with birth certificates had increased by 1·5% (95% CI −7·1 to 10·1) in the UCT group and by 16·4% (7·8–25·0) in the CCT group by the end of the intervention period. The proportions of children aged 0–4 years with complete vaccination records was 3·1% (−3·8 to 9·9) greater in the UCT group and 1·8% (−5·0 to 8·7) greater in the CCT group than in the control group. The proportions of children aged 6–12 years who attended school at least 80% of the time was 7·2% (0·8–13·7) higher in the UCT group and 7·6% (1·2–14·1) in the CCT group than in the control group. Interpretation Our results support strategies to integrate cash transfers into social welfare programming in sub-Saharan Africa, but further evidence is needed for the comparative effectiveness of UCT and CCT programmes in this region. Funding Wellcome Trust, the World Bank through the Partnership for Child Development, and the Programme of Support for the Zimbabwe National Action Plan for Orphans and Vulnerable Children.
Summary Background The post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess resource requirements and ...cost-effectiveness of strategies to achieve these targets in China, India, and South Africa. Methods We examined intervention scenarios developed in consultation with country stakeholders, which scaled up existing interventions to high but feasible coverage by 2025. Nine independent modelling groups collaborated to estimate policy outcomes, and we estimated the cost of each scenario by synthesising service use estimates, empirical cost data, and expert opinion on implementation strategies. We estimated health effects (ie, disability-adjusted life-years averted) and resource implications for 2016–35, including patient-incurred costs. To assess resource requirements and cost-effectiveness, we compared scenarios with a base case representing continued current practice. Findings Incremental tuberculosis service costs differed by scenario and country, and in some cases they more than doubled existing funding needs. In general, expansion of tuberculosis services substantially reduced patient-incurred costs and, in India and China, produced net cost savings for most interventions under a societal perspective. In all three countries, expansion of access to care produced substantial health gains. Compared with current practice and conventional cost-effectiveness thresholds, most intervention approaches seemed highly cost-effective. Interpretation Expansion of tuberculosis services seems cost-effective for high-burden countries and could generate substantial health and economic benefits for patients, although substantial new funding would be required. Further work to determine the optimal intervention mix for each country is necessary. Funding Bill & Melinda Gates Foundation.
Abstract Malignant rhabdoid tumors (MRTs) are well recognized in the kidney and extrarenal sites such as soft tissues, retroperitoneum, and bladder but are classified as atypical teratoid/rhabdoid ...tumors in the central nervous system. The unifying features of both extracranial MRT and atypical teratoid/rhabdoid tumors are the exon deletions/mutations of the SMARCB1 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) gene in 22q11.23 and resulting loss of SMARCB1/INI1 (integrase interactor 1) protein expression by immunohistochemistry. We herein report a case of extrarenal rhabdoid tumor confined to the bladder in a 3-year-old child, diagnosed by histopathology and confirmed by immunohistochemical and molecular studies. This is only the fourth molecularly proven primary MRT of the bladder to be reported. The patient's peripheral blood was negative for the deletions observed in the tumor, thereby confirming a sporadic origin for the tumor. Given the possible dismal outcome, urgency for definitive diagnosis to institute intensive multimodality therapy, histopathologic differential diagnosis with rhabdomyosarcoma and urothelial carcinoma with rhabdoid features, and lack of consensus management guidelines, oncologists, urologists, and pathologists must be aware of this entity. Evaluation for a germ line SMARCB1 alteration may greatly aid risk stratification and family planning.
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