Current HIV Research (v.9, #6)

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Harnessing the Prevention Benefits of Antiretroviral Therapy to Address HIV and Tuberculosis by Reuben Granich, Ying-Ru Lo, Amitabh B. Suthar, Marco Vitoria, Rachel Baggaley, Carla Makhlouf Obermeyer, Craig McClure, Yves Souteyrand, Jos Perriens, James G. Kahn, Rod Bennett, Caoimhe Smyth, Brian Williams, Julio Montaner, Gottfried Hirnschall (355-366).
After 30 years we are still struggling to address a devastating HIV pandemic in which over 25 million peoplehave died. In 2010, an estimated 34 million people were living with HIV, around 70% of whom live in sub-SaharanAfrica. 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 thisachievement, around 9 million people were eligible and still in need of treatment, and new infections (approximately 2.6million in 2010 alone) continue to add to the future caseload. This combined with the international fiscal crisis has led to agrowing concern regarding weakening of the international commitment to universal access and delivery of the MillenniumDevelopment Goals by 2015. The recently launched UNAIDS/WHO Treatment 2.0 platform calls for acceleratedsimplification of ART, in line with a public health approach, to achieve and sustain universal access to ART, includingmaximizing the HIV and TB preventive benefit of ART by treating people earlier, in line with WHO 2010 normativeguidance. The potential individual and public health prevention benefits of using treatment in the prevention of HIV andTB enhance the value of the universal access pledge from a life-saving initiative, to a strategic investment aimed at endingthe HIV epidemic. This review analyzes the gaps and summarizes the evidence regarding ART in the prevention of HIVand TB.

Modelling the Impact of Antiretroviral Therapy on the Epidemic of HIV by Brian G. Williams, Viviane Lima, Eleanor Gouws (367-382).
Thirty years after HIV first appeared it has killed close to 30 million people but transmission continuesunchecked. In 2009, an estimated 1.8 million lives were lost and 2.6 million more people were infected with HIV [1]. Tocut transmission, many social, behavioural and biomedical interventions have been developed, tested and tried but havehad little impact on the epidemic in most countries. One substantial success has been the development of combinationantiretroviral therapy (ART) that reduces viral load and restores immune function. This raises the possibility of usingART not only to treat people but also to prevent new HIV infections. Here we consider the impact of ART on thetransmission of HIV and show how it could help to control the epidemic.Much needs to be known and understood concerning the impact of early treatment with ART on the prognosis forindividual patients and on transmission. We review the current literature on factors associated with modelling treatmentfor prevention and illustrate the potential impact using existing models. We focus on generalized epidemics in sub-Saharan Africa, with an emphasis on South Africa, where transmission is mainly heterosexual and which account for anestimated 17% of all people living with HIV. We also make reference to epidemics among men who have sex with menand injection drug users where appropriate. We discuss ways in which using treatment as prevention can be taken forwardknowing that this can only be the beginning of what must become an inclusive dialogue among all of those concerned tostop acquired immune deficiency syndrome (AIDS).

Antiretroviral therapy (ART) has been remarkably effective in ameliorating Human Immunodeficiency Virus(HIV)-associated morbidity and mortality. The rapid decline in viral load during ART also presents an opportunity todevelop a “treatment as prevention” strategy in order to reduce HIV transmission at a population level. Modellingexercises have demonstrated that for this strategy to be effective, early initiation of ART with high coverage of the HIVinfectedpopulation will be required. The HIV epidemic has fueled a resurgence of tuberculosis (TB) particularly in sub-Saharan Africa and widespread early initiation of ART could also impact this epidemic via several mechanisms. Theproportion of patients with low CD4 cell counts who are at high risk of TB disease from progression of both latent andnew TB infection would be greatly reduced. Entry into a life-long ART program provides an ongoing opportunity forintensified TB case finding among the HIV-infected population. Regular screening for HIV infection also presents anopportunity for intensified TB case finding in the general population. The combined effect of reduced progression ofinfection to disease and intensified case finding could reduce the overall prevalence of infectious TB, thereby furtherdecreasing TB transmission. In addition, decreasing prevalence of HIV infection would reduce the TB-susceptible poolwithin the population. The ‘test and treat’ strategy therefore has potential to reduce the TB risk at both an individual and apopulation level. In this paper we explore the expected “TB dividend” of wider access to ART and also explore thepotential of the ‘test and treat’ strategy to impact on TB transmission, particularly in the heavily burdened setting of sub-Saharan Africa.

The Unrealized Potential of Addiction Science in Curbing the HIV Epidemic by Nora D. Volkow, Ruben D. Baler, Jacques L. Normand (393-395).
The stubbornly high incidence of new HIV infections belies the overwhelming evidence showing that sustainedhighly active antiretroviral therapy (HAART) has the power to dramatically reduce the spread of HIV infection andforever change the face of this devastating epidemic. One of the main contributors to this public health paradox is theongoing HIV epidemic among substance users who contribute significantly to HIV infection rates through injection druguse and high-risk sexual behaviours. Current evidence clearly shows that, in order to fill this gap, we need to integratesubstance abuse treatment with HIV treatment programmes and provide substance abusers with universal access to HIVtreatment through a focussed effort to seek, test, treat, and retain hard-to-reach high risk individuals. These aims willrequire structural changes in the health care system to overcome many of the obstacles that have inhibited the merging ofsubstance abuse treatment with HIV programmes for far too long.

Articulating A Rights-Based Approach to HIV Treatment and Prevention Interventions by David Barr, Joseph J. Amon, Michaela Clayton (396-404).
Since the beginning of the epidemic, the protection of human rights has been an integral component in theresponse to Human Immunodeficiency Virus (HIV). The high degree of stigma and discrimination associated withacquired immune deficiency syndrome (AIDS) has made human rights protection not only a priority to ensure the rightsof people living with and at-risk for HIV, but to address public health goals as well. Advances in understanding the impactof antiretroviral treatment on HIV prevention provide exciting opportunities and even a paradigm shift in terms of AIDSprevention. However, this potential cannot be reached unless the advancement of human rights is a primary component oftreatment and prevention programme and policy development. The use of antiretroviral treatment as prevention reinforcesthe value of basic principles related to the dignity and agency of people living with HIV to participate in the design andimplementation of programmes, to be informed and to make informed decisions about their health and lives, to beprotected from harm, and to have opportunities to seek redress and accountability for abuses. The possibility of using HIVtreatment as a prevention tool means that now, more than ever, legal reform and community empowerment andmobilisation are necessary to realize the rights and health of people affected by HIV.

Cost-Effectiveness of Antiretroviral Therapy for Prevention by James G. Kahn, Elliot A. Marseille, Rod Bennett, Brian G. Williams, Reuben Granich (405-415).
Recent empirical studies and analyses have heightened interest in the use of expanded antiretroviral therapy(ART) for prevention of HIV transmission. However, ART is expensive, approximately $600 per person per year, raisingissues of the cost and cost-effectiveness of ambitious ART expansion. The goal of this review is to equip the reader withthe conceptual tools and substantive background needed to understand and evaluate the policy and programmaticimplications of cost-effectiveness assessments of ART for prevention. We provide this review in six sections. We start byintroducing and explaining basic concepts of health economics as they relate to this issue, including resources, costs,health metrics (such as Disability-Adjusted Life Years), and different types of economic analysis. We then reviewresearch on the cost and cost-effectiveness of ART as treatment, and on the cost-effectiveness of traditional HIVprevention. We describe critical issues in the epidemic impact of ART, such as suppression of transmission and the role ofthe acute phase of infection. We then present a conceptual model for conducting and interpreting cost-effectivenessanalyses of ART as prevention, and review the existing preliminary estimates in this area. We end with a discussion offuture directions for programmatic demonstrations and evaluation.

Costing Human Rights and Community Support Interventions as a Part of Universal Access to HIV Treatment and Care in a Southern African Setting by Louisa Jones, Paula Akugizibwe, Michaela Clayton, Joseph J. Amon, Miriam Lewis Sabin, Rod Bennett, Christine Stegling, Rachel Baggaley, James G. Kahn, Charles B. Holmes, Navneet Garg, Carla Makhlouf Obermeyer, Christina DeFilippo Mack, Phoebe Williams, Caoimhe Smyth, Marco Vitoria, Siobhan Crowley, Brian Williams, Craig McClure, Reuben Granich, Gottfried Hirnschall (416-428).
Expanding access to antiretroviral therapy (ART) has both individual health benefits and potential to decreaseHIV incidence. Ensuring access to HIV services is a significant human rights issue and successful programmes requireadequate human rights protections and community support. However, the cost of specific human rights and communitysupport interventions for equitable, sustainable and non-discriminatory access to ART are not well described. Humanrights and community support interventions were identified using the literature and through consultations with experts.Specific costs were then determined for these health sector interventions. Population and epidemic data were providedthrough the Statistics South Africa 2009 national mid-year estimates. Costs of scale up of HIV prevention and treatmentwere taken from recently published estimates. Interventions addressed access to services, minimising stigma anddiscrimination against people living with HIV, confidentiality, informed consent and counselling quality. Integrated HIVprogramme interventions included training for counsellors, ‘Know Your Rights’ information desks, outreach campaignsfor most at risk populations, and adherence support. Complementary measures included post-service interviews, humanrights abuse monitoring, transportation costs, legal assistance, and funding for human rights and community supportorganisations. Other essential non-health sector interventions were identified but not included in the costing framework.The annual costs for the human rights and community support interventions are United States (US) $63.8 million (US$1.22 per capita), representing 1.5% of total health sector HIV programme costs. Respect for human rights andcommunity engagement can be understood both as an obligation of expanded ART programmes and as a criticallyimportant factor in their success. Basic rights-based and community support interventions constitute only a smallpercentage of overall programmes costs. ART programs should consider measuring the cost and impact of human rightsand community support interventions as key aspects of successful programme expansion.

Universal Testing and Treatment as an HIV Prevention Strategy: Research Questions and Methods by Richard Hayes, Kalpana Sabapathy, Sarah Fidler (429-445).
Achieving high coverage of antiretroviral treatment (ART) in resource-poor settings will become increasinglydifficult unless HIV incidence can be reduced substantially. Universal voluntary counselling and testing followed byimmediate initiation of ART for all those diagnosed HIV-positive (universal testing and treatment, UTT) has the potentialto reduce HIV incidence dramatically but would be very challenging and costly to deliver in the short term. Earlymodelling work in this field has been criticised for making unduly optimistic assumptions about the uptake and coverageof interventions. In future work, it is important that model parameters are realistic and based where possible on empiricaldata. Rigorous research evidence is needed before the UTT approach could be considered for wide-scale implementation.This paper reviews the main areas that need to be explored. We consider in turn research questions related to the provisionof services for universal testing, services for immediate treatment of HIV-positives and the population-level impact ofUTT, and the research methods that could be used to address these questions. Ideally, initial feasibility studies should becarried out to investigate the acceptability, feasibility and uptake of UTT services. If these studies produce promisingresults, there would be a strong case for a cluster-randomised trial to measure the impact of a UTT intervention on HIVincidence, and we consider the main design features of such a trial.

Antiretroviral Therapy in Prevention of HIV and TB: Update on Current Research Efforts by Reuben Granich, Somya Gupta, Amitabh B. Suthar, Caoimhe Smyth, David Hoos, Mariangela Simao, Catherine Hankins, Bernard Schwartlander, Renee Ridzon, Brigitte Bazin, Brian Williams, Ying-Ru Lo, Craig McClure, Julio Montaner, Gottfried Hirnschall (446-469).
There is considerable scientific evidence supporting the use of antiretroviral therapy (ART) in prevention ofhuman immunodeficiency virus (HIV) and tuberculosis (TB) infections. The complex nature of the HIV and TBprevention responses, resource constraints, remaining questions about cost and feasibility, and the need to use a solidevidence base to make policy decisions, and the implementation challenges to translating trial data to operational settingsrequire a well-organised and coordinated response to research in this area. To this end, we aimed to catalogue the ongoingand planned research activities that evaluate the impact of ART plus other interventions on HIV- and/or TB-relatedmorbidity, mortality, risk behaviour, HIV incidence and transmission. Using a limited search methodology, 50 projectswere identified examining ART as prevention, representing 5 regions and 52 countries with a global distribution. Thereare 24 randomised controlled clinical trials with at least 12 large randomised individual or community cluster trials inresource-constrained settings that are in the planning or early implementation stages. There is considerable heterogeneitybetween studies in terms of methodology, interventions and geographical location. While the identified studies willundoubtedly advance our understanding of the efficacy and effectiveness of ART for prevention, some key questions mayremain unanswered or only partially answered. The large number and wide variety of research projects emphasise theimportance of this research issue and clearly demonstrate the potential for synergies, partnerships and coordination acrossfunding agencies.

Antiretroviral therapy (ART), for those who have access, has revolutionised the morbidity and mortalityconsequences of HIV infection. By the end of 2010, 6.6 million people living with HIV in low- and middle-incomecountries were receiving ART, a dramatic 20-fold increase since 2001, saving millions of lives. In addition to the impactof ART on the health of those living with HIV, recent randomised controlled trials demonstrate the additional impact ofART in reducing HIV transmission. With this double effect, ART is a game changer in the response to AIDS. With otheradvances over the past year, we now have a set of effective tools to stop the transmission of the virus and to keep peopleliving with HIV healthy and productive. It is now the collective responsibility of researchers and implementers, ofgovernments, the private sector and civil society, to identify and overcome the challenges and translate the science intoreal results for people. At the recent United Nations High Level Meeting on AIDS, Member States endorsed ambitioustargets including to reach 15 million people living with HIV with ART and to cut sexual transmission of HIV by half by2015. The declaration also calls for additional resources of 22 to 24 billion dollars by 2015 as an investment that will yieldreturns in multiples.