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Global scale-up of antiretroviral therapy (ART) in low- and middle-income countries (LMICs) is an unprecedented public health achievement. With planned efforts of expanded ART access including earlier treatment initiation and the use of antiretroviral (ARV) drugs for prophylaxis, increasing levels of HIV drug resistance (HIVDR) are expected. Several factors may lead to selection and transmission of significant HIVDR in LMICs, which will lead to decreased population-level efficacy of standard first- and second-line ART regimens. These factors include low genetic barrier of some ARVs to resistance development, drug–drug interactions, inappropriate prescribing practices, interruption of drug supply, poor retention in care and lack of routine viral load monitoring. To maximize long-term effectiveness of available ARVs, policy makers and programme managers in LMICs should routinely monitor programme factors associated with emergence and transmission of HIVDR and implement routine HIVDR surveillance following standardized methods. When surveillance results suggest the need for action, specific public health interventions must be taken to adjust ART programme functioning to minimize further emergence and transmission of HIVDR. In this paper, we review ARV drug, HIV, patient and programme-related determinants of HIVDR. Additionally, we summarize the World Health Orgnization's global HIVDR surveillance and prevention strategy and describe resulting public health and policy implications.

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.

Expanding access to antiretroviral therapy (ART) has both individual health benefits and potential to decrease HIV incidence. Ensuring access to HIV services is a significant human rights issue and successful programmes require adequate human rights protections and community support. However, the cost of specific human rights and community support interventions for equitable, sustainable and non-discriminatory access to ART are not well described. Human rights 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 provided through the Statistics South Africa 2009 national mid-year estimates. Costs of scale up of HIV prevention and treatment were taken from recently published estimates. Interventions addressed access to services, minimising stigma and discrimination against people living with HIV, confidentiality, informed consent and counselling quality. Integrated HIV programme interventions included training for counsellors, ‘Know Your Rights’ information desks, outreach campaigns for most at risk populations, and adherence support. Complementary measures included post-service interviews, human rights abuse monitoring, transportation costs, legal assistance, and funding for human rights and community support organisations. 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 and community engagement can be understood both as an obligation of expanded ART programmes and as a critically important factor in their success. Basic rights-based and community support interventions constitute only a small percentage of overall programmes costs. ART programs should consider measuring the cost and impact of human rights and community support interventions as key aspects of successful programme expansion

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.

Substantial changes are needed to achieve a more targeted and strategic approach to investment in the response to the HIV/AIDS epidemic that will yield long-term dividends. Until now, advocacy for resources has been done on the basis of a commodity approach that encouraged scaling up of numerous strategies in parallel, irrespective of their relative effects. We propose a strategic investment framework that is intended to support better management of national and international HIV/AIDS responses than exists with the present system. Our framework incorporates major efficiency gains through community mobilisation, synergies between programme elements, and benefits of the extension of antiretroviral therapy for prevention of HIV transmission. It proposes three categories of investment, consisting of six basic programmatic activities, interventions that create an enabling environment to achieve maximum effectiveness, and programmatic efforts in other health and development sectors related to HIV/AIDS. The yearly cost of achievement of universal access to HIV prevention, treatment, care, and support by 2015 is estimated at no less than US$22 billion. Implementation of the new investment framework would avert 12·2 million new HIV infections and 7·4 million deaths from AIDS between 2011 and 2020 compared with continuation of present approaches, and result in 29·4 million life-years gained. The framework is cost effective at $1060 per life-year gained, and the additional investment proposed would be largely offset from savings in treatment costs alone.