The Impact of Antiretroviral Therapy on the HIV Epidemic in South Africa

The Human Immunodeficiency Virus (HIV) is the cause of Acquired Immune Deficiency Syndrome (AIDS), a lethal disease characterized by the destruction of the immune system. At the end of 2010, there were about 34 million people infected with HIV worldwide. The epicenter of the HIV pandemic lies in sub-Saharan Africa (figure 1.1): with only 12% of the world’s population, 68% of all people living with HIV live in the subcontinent. Although the number of new infections worldwide declined over the past decades, there were an estimated 2.7 million acquired the infection in 2010 [3]. Especially countries in Eastern and Southern Africa are heavily affected by the pandemic. In countries like Botswana or Swaziland prevalence levels in the adult population are as high as 20 to 25%. South Africa is the country with the largest HIVinfected population worldwide. With prevalence levels of about 15% in the population aged over 15 years, the country has about 6 million people living with HIV. Over the past few years, the number of new infections in the country declined, yet incidence levels remain considerable. In mid-2010, about 1.5 million people infected with HIV were receiving antiretroviral therapy (ART), while a further 1.5 million are estimated to be eligible for treatment

Which delivery model innovations can support sustainable HIV treatment?

The rapid scale-up of antiretroviral treatment (ART) for HIV since the mid-2000s, mostly through disease-specific or “vertical” programmes, has been a highly successful undertaking, which averted millions of deaths and prevented many new infections. However, the dynamics of the HIV epidemic and changing political and financial commitment to fight the disease will likely require new models for the delivery of ART over the coming decades if the promises of universal treatment are to be met. Delivery model innovations for ART are intended to improve both the effectiveness and efficiency of the HIV treatment cascade, reaching new people who require ART and providing ART to more people without an increase in resources. We describe twelve models for ART delivery, which could be achieved through five categories of delivery innovations: integrating ART (“vertical ART plus”, “partially-integrated ART” and “fully-integrated ART”); modifying steps in the ART value chain (“professional task-shifted ART”, “people task-shifted ART” and “technology-supported ART”); eliminating steps in the ART value chain (“immediate ART” and “less frequent ART pick-up”); changing ART locations (“private-sector ART”, “traditional-sector ART” and “ART outside the health sector”); and keeping the status quo (“vertical ART”). The different delivery model innovations are not mutually exclusive and several could be combined, such as “vertical ART plus” with “task-shifted ART”. Suitability of the models will highly depend on local and national contexts, including existing health systems resources, available funding, and type of HIV epidemic. Future implementation research needs to identify which models are the best fit for different contexts

Priority setting for universal health coverage: We need evidence-informed deliberative processes, not just more evidence on cost-effectiveness

Priority setting of health interventions is generally considered as a valuable approach to support low- and middle-income countries (LMICs) in their strive for universal health coverage (UHC). However, present initiatives on priority setting are mainly geared towards the development of more cost-effectiveness information, and this evidence does not sufficiently support countries to make optimal choices. The reason is that priority setting is in reality a value-laden political process in which multiple criteria beyond cost-effectiveness are important, and stakeholders often justifiably disagree about the relative importance of these criteria. Here, we propose the use of ‘evidence-informed deliberative processes’ as an approach that does explicitly recognise priority setting as a political process and an intrinsically complex task. In these processes, deliberation between stakeholders is crucial to identify, reflect and learn about the meaning and importance of values, informed by evidence on these values. Such processes then result in the use of a broader range of explicit criteria that can be seen as the product of both international learning (‘core’ criteria, which include eg, cost-effectiveness, priority to the worse off, and financial protection) and learning among local stakeholders (‘contextual’ criteria). We believe that, with these evidence-informed deliberative processes in place, priority setting can provide a more meaningful contribution to achieving UHC

Mapping and characterising areas with high levels of HIV transmission in sub-Saharan Africa: A geospatial analysis of national survey data

BACKGROUND: In the generalised epidemics of sub-Saharan Africa (SSA), human immunodeficiency virus (HIV) prevalence shows patterns of clustered micro-epidemics. We mapped and characterised these high-prevalence areas for young adults (15-29 years of age), as a proxy for areas with high levels of transmission, for 7 countries in Eastern and Southern Africa: Kenya, Malawi, Mozambique, Tanzania, Uganda, Zambia, and Zimbabwe. METHODS AND FINDINGS: We used geolocated survey data from the most recent United States Agency for International Development (USAID) demographic and health surveys (DHSs) and AIDS indicator surveys (AISs) (collected between 2008-2009 and 2015-2016), which included about 113,000 adults-of which there were about 53,000 young adults (27,000 women, 28,000 men)-from over 3,500 sample locations. First, ordinary kriging was applied to predict HIV prevalence at unmeasured locations. Second, we explored to what extent behavioural, socioeconomic, and environmental factors explain HIV prevalence at the individual- and sample-location level, by developing a series of multilevel multivariable logistic regression models and geospatially visualising unexplained model heterogeneity. National-level HIV prevalence for young adults ranged from 2.2% in Tanzania to 7.7% in Mozambique. However, at the subnational level, we found areas with prevalence among young adults as high as 11% or 15% alternating with areas with prevalence between 0% and 2%, suggesting the existence of areas with high levels of transmission Overall, 15.6% of heterogeneity could be explained by an interplay of known behavioural, socioeconomic, and environmental factors. Maps of the interpolated random effect estimates show that environmental variables, representing indicators of economic activity, were most powerful in explaining high-prevalence areas. Main study limitations were the inability to infer causality due to the cross-sectional nature of the surveys and the likely under-sampling of key populations in the surveys. CONCLUSIONS: We found that, among young adults, micro-epidemics of relatively high HIV prevalence alternate with areas of very low prevalence, clearly illustrating the existence of areas with high levels of transmission. These areas are partially characterised by high economic activity, relatively high socioeconomic status, and risky sexual behaviour. Localised HIV prevention interventions specifically tailored to the populations at risk will be essential to curb transmission. More fine-scale geospatial mapping of key populations,-such as sex workers and migrant populations-could help us further understand the drivers of these areas with high levels of transmission and help us determine how they fuel the generalised epidemics in SSA

The role of acquired immunity in the spread of human papillomavirus (HPV): Explorations with a microsimulation model

__Background:__ Knowledge of the natural history of human papillomavirus (HPV), in particular the role of immunity, is crucial in estimating the (cost-) effectiveness of HPV vaccination and cervical cancer screening strategies, because naturally acquired immunity after clearing an infection may already protect part of the risk population against new HPV infections. __Methods:__ We used STDSIM, an established stochastic microsimulation model, quantified to the Netherlands. We explored different assumptions regarding the natural history of HPV-16 and HPV-18, and estimated the transmission probabilities and durations of acquired immunity necessary to reproduce age-specific prevalence. __Results:__ A model without acquired immunity cannot reproduce the age-specific patterns of HPV. Also, it is necessary to assume a high degree of individual variation in the duration of infection and acquired immunity. According to the model estimates, on average 20% of women are immune for HPV-16 and 15% for HPV-18. After an HPV-16 infection, 50% are immune for less than 1 year, whereas 20% exceed 30 years. For HPV-18, up to 12% of the individuals are immune for less than 1 year, and about 50% over 30 years. Almost half of all women will never acquire HPV-16 or HPV-18. __Conclusions:__ Acquired immunity likely plays a major role in HPV epidemiology, but its duration shows substantial variation. Combined with the lifetime risk, this explains to a large extent why many women will never develop cervical cancer

The Socioeconomic Benefit to Individuals of Achieving the 2020 Targets for Five Preventive Chemotherapy Neglected Tropical Diseases

Background: Lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminths (STH) and trachoma represent the five most prevalent neglected tropical diseases (NTDs). They can be controlled or eliminated by means of safe and cost-effective interventions delivered through programs of Mass Drug Administration (MDA)—also named Preventive Chemotherapy (PCT). The WHO defined targets for NTD control/elimination by 2020, reinforced by the 2012 London Declaration, which, if achieved, would result in dramatic health gains. We estimated the potential economic benefit of achieving these targets, focusing specifically on productivity and out-of-pocket payments. Methods: Productivity loss was calculated by combining disease frequency with productivity loss from the disease, from the perspective of affected individuals. Productivity gain was calculated by deducting the total loss expected in the target achievement scenario from the loss in a counterfactual scenario where it was assumed the pre-intervention situation in 1990 regarding NTDs would continue unabated until 2030. Economic benefits from out-of-pocket payments (OPPs) were calculated similarly. Benefits are reported in 2005 US$(purchasing power parity-adjusted and discounted at 3 Results: The economic benefit from productivity gain was estimated to be I$251 billion in 2011–2020 and I$313 billion in 2021–2030, considerably greater than the total OPPs averted of I$0.72 billion and I$0.96 billion in the same periods. The net benefit is expected to be US$ 27.4 and US$ 42.8 for every dollar invested during the same periods. Impact varies between NTDs and regions, since it is determined by disease prevalence and extent of disease-related p

Socioeconomic benefit to individuals of achieving 2020 targets for four neglected tropical diseases controlled/eliminated by innovative and intensified disease management

__Background__ The control or elimination of neglected tropical diseases (NTDs) has targets defined by the WHO for 2020, reinforced by the 2012 London Declaration. We estimated the economic impact to individuals of meeting these targets for human African trypanosomiasis, leprosy, visceral leishmaniasis and Chagas disease, NTDs controlled or eliminated by innovative and intensified disease management (IDM). __Methods__ A systematic literature review identified information on productivity loss and out-of-pocket payments (OPPs) related to these NTDs, which were combined with projections of the number of people suffering from each NTD, country and year for 2011±2020 and 2021±2030. The ideal scenario in which the WHO's 2020 targets are met was compared with a counterfactual scenario that assumed the situation of 1990 stayed unaltered. Economic benefit equaled the difference between the two scenarios. Values are reported in 2005 US, purchasing power parity-adjusted, discounted at 3% per annum from 2010. Probabilistic sensitivity analyses were used to quantify the degree of uncertainty around the base-case impact estimate. __Results__ The total global productivity gained for the four IDM-NTDs was I 23.1 (I$15.9 ±I$ 34.0) billion in 2011±2020 and I$35.9 (I$ 25.0 ±I$51.9) billion in 2021±2030 (2.5th and 97.5th percentiles in brackets), corresponding to US$ 10.7 billion (US$7.4 ±US$ 15.7) and US$16.6 billion (US$ 11.6 ±US$24.0). Reduction in OPPs was I$ 14 billion (US$6.7 billion) and I$ 18 billion (US$ 10.4 billion) for the same periods. __Conclusions__ We faced important limitations to our work, such as finding no OPPs for leprosy. We had to combine limited data from various sources, heterogeneous background, and of variable quality. Nevertheless, based on conservative assumptions and subsequent uncertainty analyses, we estimate that the benefits of achieving the targets are considerable. Under plausible scenarios, the economic benefits far exceed the necessary investments by endemic country governments and their development partners. Given the higher frequency of NTDs among the poorest households, these investments represent good value for money in the effort to improve well-being, distribute the world's prosperity more equitably and reduce inequity

Translating international HIV treatment guidelines into local priorities in Indonesia

Objective: International guidelines recommend countries to expand antiretroviral therapy (ART) to all HIV-infected individuals and establish local-level priorities in relation to other treatment, prevention and mitigation interventions through fair processes. However, no practical guidance is provided for such priority-setting processes. Evidence-informed deliberative processes (EDPs) fill this gap and combine stakeholder deliberation to incorporate relevant social values with rational decision-making informed by evidence on these values. This study reports on the first-time implementation and evaluation of an EDP in HIV control, organised to support the AIDS Commission in West Java province, Indonesia, in the development of its strategic plan for 2014–2018. Methods: Under the responsibility of the provincial AIDS Commission, an EDP was implemented to select priority interventions using six steps: (i) situational analysis; (ii) formation of a multistakeholder Consultation Panel; (iii) selection of criteria; (iv) identification and assessment of interventions’ performance; (v) deliberation; and (vi) selection of funding and implementing institutions. An independent researcher conducted in-depth interviews (n = 21) with panel members to evaluate the process. Results: The Consultation Pa

Concerted Efforts to Control or Eliminate Neglected Tropical Diseases

Background: The London Declaration (2012) was formulated to support and focus the control and elimination of ten neglected tropical diseases (NTDs), with targets for 2020 as formulated by the WHO Roadmap. Five NTDs (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths and trachoma) are to be controlled by preventive chemotherapy (PCT), and four (Chagas’ disease, human African trypanosomiasis, leprosy and visceral leishmaniasis) by innovative and intensified disease management (IDM). Guinea worm, virtually eradicated, is not considered here. We aim to estimate the global health impact of meeting these targets in terms of averted morbidity, mortality, and disability adjusted life years (DALYs). Methods: The Global Burden of Disease (GBD) 2010 study provides prevalence and burden estimates for all nine NTDs in 1990 and 2010, by country, age and sex, which were taken as the basis for our calculations. Estimates for other years were obtained by interpolating between 1990 (or the start-year of large-scale control efforts) and 2010, and further extrapolating until 2030, such that the 2020 targets were met. The NTD disease manifestations considered in the GBD study were analyzed as either reversible or irreversible. Health impacts were assessed by comparing the results of achieving the targets with the counterfactual, construed as the health burden had the 1990 (or 2010 if higher) situation continued unabated. Principle Findings/Conclusions: Our calculations show that meeting the targets will lead to about 600 million averted DALYs in the period 2011–2030, nearly equally distributed between PCT and IDM-NTDs, with the health gain amongst PCT-NTDs mostly (96%) due to averted disability and amongst IDM-NTDs largely (95%) from averted mortality. These health gains include about 150 million averted irreversible disease manifestations (e.g. blindness) and 5 million averted deaths. Control of soil-transmitted helminths accounts for one third of all averted DALYs. We conclude that the projected health impact of the London Declaration justifies the required efforts