Somya Gupta

Antiretroviral Therapy in Prevention of HIV and TB: Update on Current Research Efforts

There is considerable scientific evidence supporting the use of antiretroviral therapy (ART) in prevention of human immunodeficiency virus (HIV) and tuberculosis (TB) infections. The complex nature of the HIV and TB prevention responses, resource constraints, remaining questions about cost and feasibility, and the need to use a solid evidence base to make policy decisions, and the implementation challenges to translating trial data to operational settings require a well-organised and coordinated response to research in this area. To this end, we aimed to catalogue the ongoing and planned research activities that evaluate the impact of ART plus other interventions on HIV- and/or TB-related morbidity, mortality, risk behaviour, HIV incidence and transmission. Using a limited search methodology, 50 projects were identified examining ART as prevention, representing 5 regions and 52 countries with a global distribution. There are 24 randomised controlled clinical trials with at least 12 large randomised individual or community cluster trials in resource-constrained settings that are in the planning or early implementation stages. There is considerable heterogeneity between studies in terms of methodology, interventions and geographical location. While the identified studies will undoubtedly advance our understanding of the efficacy and effectiveness of ART for prevention, some key questions may remain unanswered or only partially answered. The large number and wide variety of research projects emphasise the importance of this research issue and clearly demonstrate the potential for synergies, partnerships and coordination across funding agencies.

Trends in AIDS Deaths, New Infections and ART Coverage in the Top 30 Countries with the Highest AIDS Mortality Burden; 1990–2013

Background Antiretroviral therapy (ART) prevents human immunodeficiency virus (HIV) disease progression, mortality and transmission. We assess the impact of expanded HIV treatment for the prevention of Acquired Immunodeficiency Syndrome (AIDS)-related deaths and simulate four treatment scenarios for Nigeria and South Africa. Methods For 1990–2013, we used the Joint United Nations Programme on HIV/AIDS (UNAIDS) database to examine trends in AIDS deaths, HIV incidence and prevalence, ART coverage, annual AIDS death rate, AIDS death-to-treatment and HIV infections to treatment ratios for the top 30 countries with the highest AIDS mortality burden and compare them with data from high-income countries. We projected the 1990–2020 AIDS deaths for Nigeria and South Africa using four treatment scenarios: 1) no ART; 2) maintaining current ART coverage; 3) 90% ART coverage based on 2013 World Health Organization (WHO) ART guidelines by 2020; and 4) reaching the United Nations 90-90-90 Target by 2020. Findings In 2013, there were 1.3 million (1.1 million–1.6 million) AIDS deaths in the top 30 countries representing 87% of global AIDS deaths. Eight countries accounted for 58% of the global AIDS deaths; Nigeria and South Africa accounted for 27% of global AIDS deaths. The highest death rates per 1000 people living with HIV were in Central African Republic (91), South Sudan (82), Côte d’Ivoire (75), Cameroon (72) and Chad (71), nearly 8–10 times higher than the high-income countries. ART access in 2013 has averted as estimated 1,051,354 and 422,448 deaths in South Africa and Nigeria, respectively. Increasing ART coverage in these two countries to meet the proposed UN 90-90-90 Target by 2020 could avert 2.2 and 1.2 million deaths, respectively. Interpretation Over the past decade the expansion of access to ART averted millions of deaths. Reaching the proposed UN 90-90-90 Target by 2020 will prevent additional morbidity, mortality and HIV transmission. Despite progress, high-burden countries will need to accelerate access to ART treatment to avert millions of premature AIDS deaths and new HIV infections.

Global Policy Review of Antiretroviral Therapy Eligibility Criteria for Treatment and Prevention of HIV and Tuberculosis in Adults, Pregnant Women, and Serodiscordant Couples

Objective:This article reviews the antiretroviral therapy (ART) initiation criteria from national treatment guidelines for 70 countries and determines the extent of consistency with the current World Health Organization (WHO) recommendations. Methods:Published ART guidelines were collected from the Internet, databases, and WHO staff. ART eligibility criteria for asymptomatic people, pregnant women, people with HIV-associated tuberculosis, serodiscordant couples, injecting drug users, men who have sex with men, and sex workers were abstracted from them. Multiple regression analysis was used to determine the relation between ART eligibility criteria, ART coverage, and various population characteristics and policy interventions. Results:Of the 70 countries, 42 (60%) follow WHO’s ART guidelines for asymptomatic people and 31 (44%) for pregnant women, recommending ART at CD4 count of ⩽350 cells/mm3. Twenty-three (33%) countries recommend ART for people with HIV-associated tuberculosis irrespective of CD4 count. Nineteen countries are also recommending or considering earlier ART above CD4 count ⩽350 cell/mm3 for asymptomatic people, pregnant women, and/or serodiscordant couples. Multiple linear regression analysis shows that HIV prevalence, year of publication of guidelines, and HIV expenditure are significantly associated with published ART eligibility criteria. On average, the ART coverage is similar irrespective of published guidelines being consistent with the WHO recommendation (P < 0.53). Conclusions:Published guidelines from a significant number of countries are not following WHO recommendations. Although published guidelines may not reflect practice, it is important to adapt recommendations and services quickly to reflect the emerging science on the health and prevention benefits of earlier access to ART.

Status and methodology of publicly available national HIV care continua and 90-90-90 targets: A systematic review

Background In 2014, the Joint United Nations Program on HIV/AIDS (UNAIDS) issued treatment goals for human immunodeficiency virus (HIV). The 90-90-90 target specifies that by 2020, 90% of individuals living with HIV will know their HIV status, 90% of people with diagnosed HIV infection will receive antiretroviral treatment (ART), and 90% of those taking ART will be virally suppressed. Consistent methods and routine reporting in the public domain will be necessary for tracking progress towards the 90-90-90 target. Methods and findings For the period 2010–2016, we searched PubMed, UNAIDS country progress reports, World Health Organization (WHO), UNAIDS reports, national surveillance and program reports, United States President’s Emergency Plan for AIDS Relief (PEPFAR) Country Operational Plans, and conference presentations and/or abstracts for the latest available national HIV care continuum in the public domain. Continua of care included the number and proportion of people living with HIV (PLHIV) who are diagnosed, on ART, and virally suppressed out of the estimated number of PLHIV. We ranked the described methods for indicators to derive high-, medium-, and low-quality continuum. For 2010–2016, we identified 53 national care continua with viral suppression estimates representing 19.7 million (54%) of the 2015 global estimate of PLHIV. Of the 53, 6 (with 2% of global burden) were high quality, using standard surveillance methods to derive an overall denominator and program data from national cohorts for estimating steps in the continuum. Only nine countries in sub-Saharan Africa had care continua with viral suppression estimates. Of the 53 countries, the average proportion of the aggregate of PLHIV from all countries on ART was 48%, and the proportion of PLHIV who were virally suppressed was 40%. Seven countries (Sweden, Cambodia, United Kingdom, Switzerland, Denmark, Rwanda, and Namibia) were within 12% and 10% of achieving the 90-90-90 target for “on ART” and for “viral suppression,” respectively. The limitations to consider when interpreting the results include significant variation in methods used to determine national continua and the possibility that complete continua were not available through our comprehensive search of the public domain. Conclusions Relatively few complete national continua of care are available in the public domain, and there is considerable variation in the methods for determining progress towards the 90-90-90 target. Despite bearing the highest HIV burden, national care continua from sub-Saharan Africa were less likely to be in the public domain. A standardized monitoring and evaluation approach could improve the use of scarce resources to achieve 90-90-90 through improved transparency, accountability, and efficiency.

National HIV Care Continua for Key Populations.

We reviewed published national HIV care continua for men who have sex with men (MSM), people who inject drugs (PWID), and female sex workers (FSWs) to track progress toward the 90-90-90 target. We searched the Internet, PubMed, surveillance reports, United Nations Programme on HIV/AIDS country reports, US President’s Emergency Plan for AIDS Relief country/regional operational plans, and conference abstracts for the continua and graded them on quality. We found 12 continua for MSM, 7 for PWID, and 5 for FSW from 12 countries. HIV diagnosis, antiretroviral therapy coverage, and viral suppression varied between (1) 5% and 85%, 2% and 73%, and 1% and 72%, respectively for MSM; (2) 54% and 96%, 14% and 80%, and 8% and 68%, respectively for PWID; and (3) 27% and 63%, 8% and 16%, and 2% and 14%, respectively for FSW. Two countries, using data from national cohorts, were high quality. There are limited key population continua in the public domain. Of the few available, none have achieved 90-90-90. Improved monitoring and evaluation of key population continua is necessary to achieve the 90-90-90 target.

Progress and prospects for the control of HIV and tuberculosis in South Africa: a dynamical modelling study

BACKGROUND In September, 2016, South Africa adopted a policy of providing antiretroviral treatment to everyone infected with HIV irrespective of their CD4 cell count. Studies of universal treatment and expanded prevention of HIV differ widely in their projections of effects and the associated costs, so we did this analysis to attempt to find a consensus. METHODS We used data on HIV from the Joint UN Programme on HIV and AIDS (UNAIDS) from 1988 to 2013 and from data from WHO on tuberculosis from 1980 to to 2013 to fit a dynamical model to time trends in HIV prevalence, antiretroviral therapy (ART) coverage, and tuberculosis notification rates in South Africa. We then used the model to estimate current trends and project future patterns in HIV prevalence and incidence, AIDS-related mortality, and tuberculosis notification rates, and we used data from the South African National AIDS Council to assess current and future costs under different combinations of treatment and prevention approaches. We considered two treatment strategies: the Constant Effort strategy, in which people infected with HIV continue to start treatment at the rate in 2016, and the Expanded Treatment and Prevention (ETP) strategy, in which testing rates are increased, treatment is started immediately after HIV is detected, and prevention programmes are expanded. FINDINGS Our estimates show that HIV incidence among adults aged 15 years or older fell from 2·3% per year in 1996 to 0·65% per year in 2016, AIDS-related mortality decreased from 1·4% per year in 2006 to 0·37% per year in 2016, and both continue to fall at a relative rate of 17% per year. Our model shows that maintenance of Constant Effort will have a substantial effect on HIV but will not end AIDS, whereas ETP could end AIDS by 2030, with incidence of HIV and AIDs-related mortality rates both at less than one event per 1000 adults per year. Under ETP the annual cost of health care and prevention will increase from US

When will sub-Saharan Africa adopt HIV treatment for all?

2·3 billion in 2016 to

Pattern, Determinants, and Impact of HIV Spending on Care and Treatment in 38 High-Burden Low- and Middle-Income Countries

2·9 billion in 2018, then decrease to

CD4 Cell Count: Declining Value for Antiretroviral Therapy Eligibility

1·7 billion in 2030 and

Global Policy Review of Recommendations on Cotrimoxazole Prophylaxis among People Living with HIV

0·9 billion in 2050. Over the next 35 years, the expansion of treatment will avert an additional 3·8 million new infections, save 1·1 million lives, and save