Baseline Seroprevalence of SARS-CoV-2 Specific Antibodies in Hot Spot Areas of Great Tunis, up to 3 Months Post Disease Onset in Tunisia.

The extent of the SARS-CoV-2 circulation and the COVID-19 epidemic in Tunisia three months after virus circulation was unknown. The aim of this study was to determine the extent of SARS-CoV-2 infection among household contacts of confirmed COVID-19 cases living in Hot spot areas of Great Tunis, Tunisia by estimating the seroprevalence of antibodies anti SARS-CoV-2 and to identify factors associated to seroprevalence at the first stage of the pandemic in order to guide decision making and to constitute a baseline for further longitudinal analysis of protective immunity to SARS-CoV-2. The National Observatory of New and Emerging Diseases (ONMNE), Ministry of Health Tunisia (MoH), with the support of the Office of the World Health Organization Representative in Tunisia and the WHO Regional Office for the Eastern Mediterranean (EMRO)), conducted a household cross-sectional survey on April 2020 in Great Tunis (Tunis, Ariana, Manouba and Ben Arous). The study was based on the WHO seroepidemiological investigation protocol for SARS-CoV-2 infection. SARS-CoV-2 specific antibodies (IgG and IgM) were qualitatively detected using a lateral immunoassay that detect SARS-CoV-2 nucleocapsid protein and administered by the interviewers. The included subjects were confirmed COVID-19 cases and their households contacts resided in hot spot areas (cumulative incidence rate ≥ 10 cases/100,000 inhabitants) of Great Tunis. Results: In total, 1165 subjects were enrolled: 116 confirmed COVID-19 cases (43 active cases and 73 convalescents cases) and 1049 household contacts resided in 291 households. The median age of participants was 39.0 with 31 years' interquartile range (Min = 8 months; Max = 96 years). The sex ratio (M/F) was 0.98. Twenty-nine per cent of participants resided in Tunis. The global crude seroprevalence among household contacts was 2.5% (26/1049); 95% CI 1.6-3.6%, 4.8%; 95% CI 2.3-8.7% in Ariana governorate and 0.3%; 95% CI 0.01%-1.8% in Manouba governorate. In multivariate analysis, the associated factors independently related to seroprevalence were age ≥25 years (aOR = 5.1; 95% CI 1.2-22.0), history of travel outside Tunisia since January 2020 (aOR = 4.6; 95% CI 1.7-12.9), symptomatic illness in the previous four months (aOR = 3.5; 95% CI 1.4-9.0) and governorate of residence (p = 0.02). The low seroprevalence estimated among household contacts in Great Tunis reflect the effect of public health measures early taken (national lockdown, borders closed, remote work), the respect of non-pharmaceutical interventions and the efficacy of COVID-19 contact-tracing and case management at the first stage of the pandemic in Tunisia.

Impact of contact tracing, respect of isolation, and lockdown in reducing the number of cases infected with COVID-19. Case study: Tunisia's response from March 22 to May 4, 2020.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread rapidly across the world. Tunisia reacted early to COVID-19, resulting in a low number of infections during the first wave of the pandemic. This study was performed to model the effects of different interventions on the evolution of cases and to compare these with the Tunisian experience. METHODS: A stochastic transmission model was used to quantify the reduction in number of cases of COVID-19 with the interventions of contact tracing, compliance with isolation, and a general lockdown. RESULTS: In the model, increasing contact tracing from 20% to 80% after the first 100 cases reduced the cumulative number of infections (CNI) by 52% in 1 month. Similarly, increased compliance with isolation from 20% to 80% after the first 100 cases reduced the CNI by 45%. These reductions were smaller if the interventions were implemented after 1000 cases. A general lockdown reduced the CNI by 97% after the first 100 cases. Tunisia implemented its general lockdown after 75 cases were confirmed, which reduced the cumulative number of infected cases by 86% among the general population. CONCLUSIONS: This study shows that the early application of critical interventions contributes significantly to reducing infections and the evolution of COVID-19 in a country. Tunisia's early success with the control of COVID-19 is explained by its quick response.

Antiretroviral therapy needs: the effect of changing global guidelines.

BACKGROUND: In 2010 the WHO issued a revision of the guidelines on antiretroviral therapy (ART) for HIV infection in adults and adolescents. The recommendations included earlier diagnosis and treatment of HIV in the interest of a longer and healthier life. The current analysis explores the impact on the estimates of treatment needs of the new criteria for initiating ART compared with the previous guidelines. METHODS: The analyses are based on the national models of HIV estimates for the years 1990-2009. These models produce time series estimates of ART treatment need and HIV-related mortality. The ART need estimates based on ART eligibility criteria promoted by the 2010 WHO guidelines were compared with the need estimates based on the 2006 WHO guidelines. RESULTS: With the 2010 eligibility criteria, the proportion of people living with HIV currently in need of ART is estimated to increase from 34% to 49%. Globally, the need increases from 11.4 million (10.2-12.5 million) to 16.2 million (14.8-17.1 million). Regional differences include 7.4 million (6.4-8.4 million) to 10.6 million (9.7-11.5 million) in sub-Saharan Africa, 1.6 million (1.3-1.7 million) to 2.4 million (2.1-2.5 million) in Asia and 710 000 (610 000-780 000) to 950 000 (810 000-1.0 million) in Latin America and the Caribbean. CONCLUSIONS: When adopting the new recommendations, countries have to adapt their planning process in order to accelerate access to life saving drugs to those in need. These recommendations have a significant impact on resource needs. In addition to improving and prolonging the lives of the infected individuals, it will have the expected benefit of reducing HIV transmission and the future HIV/AIDS burden.

Derivation of parameters used in Spectrum for eligibility for antiretroviral therapy and survival on antiretroviral therapy.

BACKGROUND: The Spectrum projection package uses estimates of national HIV incidence, demographic data and other assumptions to describe the consequences of the HIV epidemic in low and middle-income countries. The default parameters used in Spectrum are updated every 2 years as new evidence becomes available to inform the model. This paper reviews the default parameters that define the course of HIV progression among adults and children in Spectrum. METHODS: For adults, data available from published and grey literature and data from the ART-LINC International epidemiologic Database to Evaluate AIDS (IeDEA) collaboration were combined to estimate survival among those who started antiretroviral therapy (ART). For children, a review of published material on survival on ART and survival on ART and cotrimoxazole was used to derive survival probabilities. Historical data on the distribution of CD4 cell counts and CD4 cell percentages by age among children who were not treated (before treatment was available) were used to progress children from seroconversion to different CD4 cell levels. RESULTS: Based on the updated evidence estimated survival among adults aged over 15 years in the first year on ART was 86%, while in subsequent years survival was estimated at 90%. Survival among children during the first year on ART was estimated to be 85% and for subsequent years 93%. DISCUSSION: The revised default parameters based on additional data will make Spectrum estimates more accurate than previous rounds of estimates.

Changes in antiretroviral therapy guidelines: implications for public health policy and public purses.

INTRODUCTION: The World Health Organization (WHO) published a revision of the antiretroviral therapy (ART) guidelines and now recommends ART for all those with a CD4 cell count ≤350/mm(3), for people with HIV and active tuberculosis (TB) or chronic active hepatitis B irrespective of CD4 cell count and all HIV-positive pregnant women. A study was undertaken to estimate the impact of the new guidelines using four countries as examples. METHODS: The current WHO/UNAIDS country projections were accessed based on the 2007 estimates for Zambia, Kenya, Cameroon and Vietnam. New projections were created using Spectrum. CD4 progression rates to need for ART were modified and compared with the baseline projections. RESULTS: The pattern of increased need for treatment is similar across the four projections. Initiating treatment at a CD4 count <250/mm(3) will increase the need for treatment by a median of 22% immediately, initiating ART at a CD4 count <350/mm(3) increases the need for treatment by a median of 60%, and the need for treatment doubles if ART is commenced at a CD4 count <500/mm(3). Initiating ART at a CD4 cell count <250/mm(3) would increase the need for treatment by a median of around 15% in 2012; initiating treatment at a CD4 count <350/mm(3) increases the need for treatment by a median of 42% across the same projections and about 84% if CD4 <500/mm(3) was used. CONCLUSIONS: The projections indicate that initiating ART earlier in the course of the disease by increasing the threshold for the initiation of ART would increase the numbers of adults in need of treatment immediately and in the future.

Leveraging Global Fund investments for health systems strengthening: a qualitative case study on Morocco's Concept Note development.

BACKGROUND: In 2014, the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) introduced a new funding model. Following notice of their 2014-2016 allocation, Morocco took the bold decision to reallocate its entire allocated investment (US$ 8 029 632) for health systems strengthening (HSS) and submitted a comprehensive request for funding solely for interventions to strengthen the health system. AIMS: To explore the specific barriers and facilitators to Morocco's novel development and submission of a cross-cutting HSS funding request to the Global Fund and to document lessons learned and recommendations for policy and programme leaders interested in leveraging Global Fund investments for health systems. METHODS: A thorough desk review of key documents and 15 in-depth qualitative interviews were conducted with key stakeholders in Morocco in 2017. RESULTS: In preparation for the funding request, Morocco carried out a comprehensive assessment of the health system, which included extensive dialogue with stakeholders and partners. This action was critical to developing a shared understanding and support for adopting a cross-cutting HSS approach. Despite concerns about potential negative effects of diverting funding from disease-specific programmes, visionary leadership advocated effectively for investing in HSS, and this paved the way for the development of a clear Concept Note requesting Global Fund financial support for the health system more broadly. CONCLUSION: Morocco was the first country in the Global Fund's Middle/East North Africa region to invest its entire Global Fund allocation in strengthening the health system. Many important lessons have been learned from this novel experience and these are presented for shared learning. This opportunity for learning is timely as countries begin preparations for the upcoming funding cycle.

Investment in HIV/AIDS programs: does it help strengthen health systems in developing countries?

BACKGROUND: There is increasing debate about whether the scaled-up investment in HIV/AIDS programs is strengthening or weakening the fragile health systems of many developing countries. This article examines and assesses the evidence and proposes ways forward. DISCUSSION: Considerably increased resources have been brought into countries for HIV/AIDS programs by major Global Health Initiatives. Among the positive impacts are the increased awareness of and priority given to public health by governments. In addition, services to people living with HIV/AIDS have rapidly expanded. In many countries infrastructure and laboratories have been strengthened, and in some, primary health care services have been improved. The effect of AIDS on the health work force has been lessened by the provision of antiretroviral treatment to HIV-infected health care workers, by training, and, to an extent, by task-shifting. However, there are reports of concerns, too - among them, a temporal association between increasing AIDS funding and stagnant reproductive health funding, and accusations that scarce personnel are siphoned off from other health care services by offers of better-paying jobs in HIV/AIDS programs. Unfortunately, there is limited hard evidence of these health system impacts. Because service delivery for AIDS has not yet reached a level that could conceivably be considered "as close to Universal Access as possible," countries and development partners must maintain the momentum of investment in HIV/AIDS programs. At the same time, it should be recognized that global action for health is even more underfunded than is the response to the HIV epidemic. The real issue is therefore not whether to fund AIDS or health systems, but how to increase funding for both. SUMMARY: The evidence is mixed - mostly positive but some negative - as to the impact on health systems of the scaled-up responses to HIV/AIDS driven primarily by global health partnerships. Current scaled-up responses to HIV/AIDS must be maintained and strengthened. Instead of endless debate about the comparative advantages of vertical and horizontal approaches, partners should focus on the best ways for investments in response to HIV to also broadly strengthen the primary health care systems.

The WHO public-health approach to antiretroviral treatment against HIV in resource-limited settings.

WHO has proposed a public-health approach to antiretroviral therapy (ART) to enable scaling-up access to treatment for HIV-positive people in developing countries, recognising that the western model of specialist physician management and advanced laboratory monitoring is not feasible in resource-poor settings. In this approach, standardised simplified treatment protocols and decentralised service delivery enable treatment to be delivered to large numbers of HIV-positive adults and children through the public and private sector. Simplified tools and approaches to clinical decision-making, centred on the "four Ss"--when to: start drug treatment; substitute for toxicity; switch after treatment failure; and stop--enable lower level health-care workers to deliver care. Simple limited formularies have driven large-scale production of fixed-dose combinations for first-line treatment for adults and lowered prices, but to ensure access to ART in the poorest countries, the care and drugs should be given free at point of service delivery. Population-based surveillance for acquired and transmitted resistance is needed to address concerns that switching regimens on the basis of clinical criteria for failure alone could lead to widespread emergence of drug-resistant virus strains. The integrated management of adult or childhood illness (IMAI/IMCI) facilitates decentralised implementation that is integrated within existing health systems. Simplified operational guidelines, tools, and training materials enable clinical teams in primary-care and second-level facilities to deliver HIV prevention, HIV care, and ART, and to use a standardised patient-tracking system.

National adult antiretroviral therapy guidelines in resource-limited countries: concordance with 2003 WHO guidelines?

AIMS: To investigate the existence of national adult antiretroviral therapy (ART) guidelines in 43 World Health Organization (WHO) '3 by 5' focus countries and compare their content with the 2003 WHO ART guidelines. METHODS: Questionnaires covered initiation of ART, selection of first or second-line ART, monitoring treatment response and toxicity and dissemination of national guidelines. Weighted concordance scores were created and country scores correlated with national indicators and WHO recommendations. RESULTS: Thirty-nine (91%) countries returned questionnaires, three of which had no national ART guidelines. Of the 36, 16 (44%) recommended to start ART based on WHO clinical staging criteria and CD4 cell count or T-lymphocyte count, 12 (33%) WHO clinical staging criteria and CD4 cell count, four (11%) only CD4 cell counts. 35 (97%) recommended a standard first-line regimen and 24 (67%) preferred stavudine + lamivudine + nevirapine; 33 (92%) recommended second-line regimens, and 24 (60%) preferred abacavir + didanosine + lopinavir/ritonavir. Thirty-one (94%) recommended CD4 cell count, possibly combined with other indicators, to monitor ART. Concordance scores were higher in countries with lower health expenditure per capita (P = 0.009) and lower GDP per capita (P < 0.03). Median concordance scores for starting ART was 100 [interquartile range (IQR), 67 to 100]; first line therapy, 70 (IQR, 60 to 80); second-line regimens, 45 (IQR, 27 to 55) and for laboratory investigations, 80 (IQR, 80 to 100). CONCLUSIONS: Most countries had developed national ART guidelines as part of a comprehensive national HIV program. Concordance with WHO recommendations was strong on starting first-line ART regimens and routine monitoring but lower for second-line recommendations.

To retain or remove user fees?: reflections on the current debate in low- and middle-income countries.

Many low- and middle-income countries continue to search for better ways of financing their health systems. Common to many of these systems are problems of inadequate resource mobilisation, as well as inefficient and inequitable use of existing resources. The poor and other vulnerable groups who need healthcare the most are also the most affected by these shortcomings. In particular, these groups have a high reliance on user fees and other out-of-pocket expenditures on health which are both impoverishing and provide a financial barrier to care. It is within this context, and in light of recent policy initiatives on user fee removal, that a debate on the role of user fees in health financing systems has recently returned. This paper provides some reflections on the recent user fees debate, drawing from the evidence presented and subsequent discussions at a recent UNICEF consultation on user fees in the health sector, and relates the debate to the wider issue of access to adequate healthcare. It is argued that, from the wealth of evidence on user fees and other health system reforms, a broad consensus is emerging. First, user fees are an important barrier to accessing health services, especially for poor people. They also negatively impact on adherence to long-term expensive treatments. However, this is offset to some extent by potentially positive impacts on quality. Secondly, user fees are not the only barrier that the poor face. As well as other cost barriers, a number of quality, information and cultural barriers must also be overcome before the poor can access adequate health services. Thirdly, initial evidence on fee abolition in Uganda suggests that this policy has improved access to outpatient services for the poor. For this to be sustainable and effective in reaching the poor, fee removal needs to be part of a broader package of reforms that includes increased budgets to offset lost fee revenue (as was the case in Uganda). Fourthly, implementation matters: if fees are to be abolished, this needs clear communication with a broad stakeholder buy-in, careful monitoring to ensure that official fees are not replaced by informal fees, and appropriate management of the alternative financing mechanisms that are replacing user fees. Fifthly, context is crucial. For instance, immediate fee removal in Cambodia would be inappropriate, given that fees replaced irregular and often high informal fees. In this context, equity funds and eventual expansion of health insurance are perhaps more viable policy options. Conversely, in countries where user fees have had significant adverse effects on access and generated only limited benefits, fee abolition is probably a more attractive policy option. Removing user fees has the potential to improve access to health services, especially for the poor, but it is not appropriate in all contexts. Analysis should move on from broad evaluations of user fees towards exploring how best to dismantle the multiple barriers to access in specific contexts.

Beyond indicators: advances in global HIV monitoring and evaluation during the PEPFAR era.

Monitoring and evaluation (M&E) is fundamental to global HIV program implementation and has been a cornerstone of the President's Emergency Plan for AIDS Relief (PEPFAR). Rapid results were crucial to demonstrating feasibility and scalability of HIV care and treatment services early in PEPFAR. When national HIV M&E systems were nascent, the rapid influx of funds and the emergency expansion of HIV services contributed to the development of uncoordinated "parallel" information systems to serve donor demands for information. Close collaboration of PEPFAR with multilateral and national partners improved harmonization of indicators, standards, methods, tools, and reports. Concurrent PEPFAR investments in surveillance, surveys, program monitoring, health information systems, and human capacity development began to show signs of progress toward sustainable country-owned systems. Awareness of the need for and usefulness of data increased, far beyond discussions of indicators and reporting. Emphasis has turned toward ensuring the quality of data and using available data to improve the quality of care. Assessing progress toward an AIDS-free generation requires that the global community can measure the reduction of new HIV infections in children and adults and monitor the coverage, quality, and outcomes of highly efficacious interventions in combination. Building national M&E systems requires sustained efforts over long periods of time with effective leadership and coordination. PEPFAR, in close collaboration with its global and national partners, is well positioned to transform the successes and challenges associated with early rapid scale-up into future opportunities for sustainable, cost-effective, country-owned programs and systems.

Expanding ART for treatment and prevention of HIV in South Africa: estimated cost and cost-effectiveness 2011-2050.

BACKGROUND: Antiretroviral Treatment (ART) significantly reduces HIV transmission. We conducted a cost-effectiveness analysis of the impact of expanded ART in South Africa. METHODS: We model a best case scenario of 90% annual HIV testing coverage in adults 15-49 years old and four ART eligibility scenarios: CD4 count <200 cells/mm(3) (current practice), CD4 count <350, CD4 count <500, all CD4 levels. 2011-2050 outcomes include deaths, disability adjusted life years (DALYs), HIV infections, cost, and cost per DALY averted. Service and ART costs reflect South African data and international generic prices. ART reduces transmission by 92%. We conducted sensitivity analyses. RESULTS: Expanding ART to CD4 count <350 cells/mm(3) prevents an estimated 265,000 (17%) and 1.3 million (15%) new HIV infections over 5 and 40 years, respectively. Cumulative deaths decline 15%, from 12.5 to 10.6 million; DALYs by 14% from 109 to 93 million over 40 years. Costs drop $504 million over 5 years and $3.9 billion over 40 years with breakeven by 2013. Compared with the current scenario, expanding to <500 prevents an additional 585,000 and 3 million new HIV infections over 5 and 40 years, respectively. Expanding to all CD4 levels decreases HIV infections by 3.3 million (45%) and costs by $10 billion over 40 years, with breakeven by 2023. By 2050, using higher ART and monitoring costs, all CD4 levels saves $0.6 billion versus current; other ART scenarios cost $9-194 per DALY averted. If ART reduces transmission by 99%, savings from all CD4 levels reach $17.5 billion. Sensitivity analyses suggest that poor retention and predominant acute phase transmission reduce DALYs averted by 26% and savings by 7%. CONCLUSION: Increasing the provision of ART to <350 cells/mm3 may significantly reduce costs while reducing the HIV burden. Feasibility including HIV testing and ART uptake, retention, and adherence should be evaluated.

Integrated surveillance of HIV care in low-income and middle-income countries.

PURPOSE OF REVIEW: HIV care should be seen as a continuum of health interventions that starts from HIV testing and counselling and ends with life-long provision of antiretroviral therapy (ART). All the interventions should be monitored with appropriate methods and indicators to constitute an integrated surveillance system of HIV care. This review outlines the different elements of this comprehensive surveillance, highlighting their public health importance. RECENT FINDINGS: Data on HIV care programmes in developing countries are generally fragmented and weak, focusing primarily on outcomes of patients on ART. A global scale-up of ART should be accompanied by robust programmatic assessment of the whole spectrum of HIV care components, which include monitoring pre-ART and ART programmatic elements, routine surveillance of HIV drug resistance, pharmacovigilance and appropriate surveillance of HIV-related mortality. SUMMARY: Comprehensive surveillance of HIV care that integrates multiple elements is needed in order to provide evidence-based data to optimize quality of care and improve survival. However, due to the increasing number of patients, the need for life-long interventions and the weakness of the health system, the implementation and sustainability of an integrated surveillance programme is challenging.

Utilization patterns and projected demand of antiretroviral drugs in low- and middle-income countries.

Background. The rapid scale-up of antiretroviral therapy in resource-limited settings has greatly increased demand for antiretroviral medicines and raised the importance of good forward planning, especially in the context of the new 2010 WHO treatment guidelines. Methods. Forecasting of the number of people receiving antiretroviral therapy from 2010 to 2012 was produced using three approaches: linear projection, country-set targets, and a restricted scenario. Two additional scenarios were then used to project the demand for various antiretroviral medicines under a fast and slower phase-out of stavudine. Results. We projected that between 7.1 million and 8.4 million people would be receiving ART by the end of 2012. Of these, 6.6% will be on second-line therapy. High variation in forecast includes reductions in the demand for d4T and d4T increases in the demand for tenofovir, emtricitabine followed by efavirenz, ritonavir, zidovudine and lopinavir; lamivudine, atazanavir, and nevirapine. Conclusion. Despite the global economic crisis and in response to the revised treatment guidelines, our model forecasts an increasing and shifting demand for antiretrovirals in resource-limited settings not only to provide treatment to new patients, but also to those switching to less toxic regimens.

Harnessing the prevention benefits of antiretroviral therapy to address HIV and tuberculosis.

After 30 years we are still struggling to address a devastating HIV pandemic in which over 25 million people have died. In 2010, an estimated 34 million people were living with HIV, around 70% of whom live in sub-Saharan Africa. Furthermore, in 2009 there were an estimated 1.2 million new HIV-associated TB cases, and tuberculosis (TB) accounted for 24% of HIV-related deaths. By the end of 2010, 6.6 million people were taking antiretroviral therapy (ART), around 42% of those in need as defined by the 2010 World Health Organization (WHO) guidelines. Despite this achievement, around 9 million people were eligible and still in need of treatment, and new infections (approximately 2.6 million in 2010 alone) continue to add to the future caseload. This combined with the international fiscal crisis has led to a growing concern regarding weakening of the international commitment to universal access and delivery of the Millennium Development Goals by 2015. The recently launched UNAIDS/WHO Treatment 2.0 platform calls for accelerated simplification of ART, in line with a public health approach, to achieve and sustain universal access to ART, including maximizing the HIV and TB preventive benefit of ART by treating people earlier, in line with WHO 2010 normative guidance. The potential individual and public health prevention benefits of using treatment in the prevention of HIV and TB enhance the value of the universal access pledge from a life-saving initiative, to a strategic investment aimed at ending the HIV epidemic. This review analyzes the gaps and summarizes the evidence regarding ART in the prevention of HIV and TB.

Estimation of antiretroviral therapy coverage: methodology and trends.

PURPOSE OF REVIEW: To present the methodology used to calculate coverage of antiretroviral therapy (ART) and review global and regional trends in ART coverage. RECENT FINDINGS: There has been a steady increase in ART coverage over the last decade with a more rapid increase in recent years. Current estimates of ART coverage are 43% for adults and 38% for children (ages 0-14 years). Methods for calculating coverage rely on good-quality patient monitoring systems in countries, and well informed models are needed to estimate the number of people in need of treatment. SUMMARY: The estimated coverage rates show that ART programs have improved over the past 8 years; however, approximately 58% (53-60%) of those people in need of ART are still not on treatment. High quality data are needed to accurately measure changes in ART coverage.

Highly active antiretroviral treatment as prevention of HIV transmission: review of scientific evidence and update.

PURPOSE OF REVIEW: An estimated 33 million people are living with HIV and universal access remains a dream for millions of people. By the end of year 2008, four million people were on treatment; however, over five million needed treatment, and in 2007, there were 2.7 million new infections. Without significant improvement in prevention, we are unlikely to meet universal access targets including the growing demand for highly active antiretroviral treatment (HAART). This review examines HAART as a potential tool for preventing HIV transmission. RECENT FINDINGS: We discuss recent scientific evidence regarding the treatment and prevention gap, importance viral load and HIV transmission, HAART and HIV transmission, when to start, HIV counseling and testing, modeling results and next steps. SUMMARY: HAART has considerable treatment and prevention benefits and it needs to be considered as a key element of combination prevention. To explore HAART as an effective prevention strategy, we recommend further evaluation of human rights and ethical considerations, clarification of research priorities and exploration of feasibility and acceptability issues.

Trends in retention on antiretroviral therapy in national programs in low-income and middle-income countries.

OBJECTIVES: To document regional and global trends for patients retained on antiretroviral therapy (ART) 12-48 months after treatment initiation, in low-income and middle-income countries. METHODS: Data reported by national programs to WHO/UNICEF/UNAIDS in 2008 were aggregated to produce regional and global estimates. The proportion of patients on ART at 12, 24, 36, and 48 months is derived from cohort monitoring systems in ART dispensing facilities. RESULTS: Of 149 countries, 70 (47%) reported on retention at 12 months, 54 (36%) at 24 months, 38 (26%) at 36 months, and 30 (20%) at 48 months. Regional and global trends showed that the majority of attrition from ART programs occurred within the first year and declined thereafter. Among countries in sub-Saharan Africa, retention on ART was estimated at 75.2% at 12 months, 66.8% at 24 months, and remained at a similar level up to 48 months. CONCLUSIONS: After high attrition in the first year, retention on ART tends to stabilize. In the literature, attrition in the first year was related to early mortality. Earlier presentation for diagnosis of HIV infection, timely screening, and access to ART are fundamental to reduce it. Countries need support in reporting on outcomes on ART.

Highly active antiretroviral treatment for the prevention of HIV transmission.

In 2007 an estimated 33 million people were living with HIV; 67% resided in sub-Saharan Africa, with 35% in eight countries alone. In 2007, there were about 1.4 million HIV-positive tuberculosis cases. Globally, approximately 4 million people had been given highly active antiretroviral therapy (HAART) by the end of 2008, but in 2007, an estimated 6.7 million were still in need of HAART and 2.7 million more became infected with HIV.Although there has been unprecedented investment in confronting HIV/AIDS - the Joint United Nations Programme on HIV/AIDS estimates $13.8 billion was spent in 2008 - a key challenge is how to address the HIV/AIDS epidemic given limited and potentially shrinking resources. Economic disparities may further exacerbate human rights issues and widen the increasingly divergent approaches to HIV prevention, care and treatment.HIV transmission only occurs from people with HIV, and viral load is the single greatest risk factor for all modes of transmission. HAART can lower viral load to nearly undetectable levels. Prevention of mother to child transmission offers proof of the concept of HAART interrupting transmission, and observational studies and previous modelling work support using HAART for prevention. Although knowing one's HIV status is key for prevention efforts, it is not known with certainty when to start HAART.Building on previous modelling work, we used an HIV/AIDS epidemic of South African intensity to explore the impact of testing all adults annually and starting persons on HAART immediately after they are diagnosed as HIV positive. This theoretical strategy would reduce annual HIV incidence and mortality to less than one case per 1000 people within 10 years and it would reduce the prevalence of HIV to less than 1% within 50 years. To explore HAART as a prevention strategy, we recommend further discussions to explore human rights and ethical considerations, clarify research priorities and review feasibility and acceptability issues.

Evaluation of three sampling methods to monitor outcomes of antiretroviral treatment programmes in low- and middle-income countries.

BACKGROUND: Retention of patients on antiretroviral therapy (ART) over time is a proxy for quality of care and an outcome indicator to monitor ART programs. Using existing databases (Antiretroviral in Lower Income Countries of the International Databases to Evaluate AIDS and Médecins Sans Frontières), we evaluated three sampling approaches to simplify the generation of outcome indicators. METHODS AND FINDINGS: We used individual patient data from 27 ART sites and included 27,201 ART-naive adults (≥15 years) who initiated ART in 2005. For each site, we generated two outcome indicators at 12 months, retention on ART and proportion of patients lost to follow-up (LFU), first using all patient data and then within a smaller group of patients selected using three sampling methods (random, systematic and consecutive sampling). For each method and each site, 500 samples were generated, and the average result was compared with the unsampled value. The 95% sampling distribution (SD) was expressed as the 2.5(th) and 97.5(th) percentile values from the 500 samples. Overall, retention on ART was 76.5% (range 58.9-88.6) and the proportion of patients LFU, 13.5% (range 0.8-31.9). Estimates of retention from sampling (n = 5696) were 76.5% (SD 75.4-77.7) for random, 76.5% (75.3-77.5) for systematic and 76.0% (74.1-78.2) for the consecutive method. Estimates for the proportion of patients LFU were 13.5% (12.6-14.5), 13.5% (12.6-14.3) and 14.0% (12.5-15.5), respectively. With consecutive sampling, 50% of sites had SD within ±5% of the unsampled site value. CONCLUSIONS: Our results suggest that random, systematic or consecutive sampling methods are feasible for monitoring ART indicators at national level. However, sampling may not produce precise estimates in some sites.