aFamily Health International, Research Triangle Park, North Carolina, USA
bCentre for the AIDS Programme of Research in South Africa (CAPRISA) and Department of Public Health and Family Medicine, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa
cDivision of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA
Correspondence to Timothy D. Mastro, MD, Family Health International, PO Box 13950, Research Triangle Park, NC 27709, USA Tel: +1 919 544 7040; e-mail: TMastro@fhi.org
Epidemiologic data have been central to providing a nuanced understanding of the HIV pandemic. From the first cases of AIDS in 1981, surveillance data have helped us understand the evolving HIV/AIDS pandemic, quantify its magnitude, track the spatial distribution of infections and modes of transmission and characterize disease progression. Evolving laboratory methods have enhanced understanding at a molecular level. The utility of these data is maximized when applied to targeting and prioritizing available prevention tools, mitigating the illness and addressing key scientific challenges.
Now, three decades into the pandemic, the importance of knowledge of the epidemic at a local level is recognized as a critical first step for shaping an appropriate response to the epidemic. Although antiretroviral therapy (ART) has transformed HIV infection from an inevitably fatal condition, HIV continues to spread unrelentingly in populations already bearing a disproportionate burden of HIV infection as well as in settings that until recently have remained relatively free of the virus. Notwithstanding the availability of several effective HIV prevention methods, limited coverage, access in populations most at risk or both have affected their impact on altering epidemic trajectories. The evolving knowledge of HIV infection has underscored the powerful synergy between HIV treatment and prevention.
Against the backdrop of a bleak epidemiological picture, this superb collection of review articles provides an important roadmap on which we need to focus our research and programmatic energies. These articles cover HIV epidemiology, risk factors, advances in HIV prevention and the changing paradigm of prevention from a focus on uninfected individuals to a continuum of prevention from uninfected to recently infected to those with established infection and growing recognition of the complex structural, social and political factors that shape vulnerability and risk.
Although we have had increasing success in limiting epidemics at the national level in countries such as Uganda, Kenya, Zimbabwe, Tanzania, Botswana, Thailand and Cambodia, HIV transmission has increased rapidly in some countries in Eastern Europe and Central Asia, highlighting the need for ongoing vigilance and improved surveillance methods [1,2]. We need renewed awareness of the importance of measuring HIV incidence rates in addition to prevalence in maturing HIV epidemics, yet efforts to develop simple tools to measure incidence have been unsuccessful to date . Molecular techniques have very elegantly demonstrated the origins of HIV infection in humans in Africa in the early twentieth century and the rapid spread and genetic diversification of HIV accompanying African urbanization . Genetic characterization of HIV strains allows for enhanced understanding of transmission patterns and networks as well as the impact of viral fitness on transmission.
The past 2 years have witnessed major setbacks in finding new biomedical and behavioral HIV prevention methods. The biggest setback was in the HIV vaccine development field . After several unsuccessful trials, the results of PRO 2000/5 in the HPTN 035 trial heralded new hope in microbicide development  and provides the first signal in humans that topical agents can prevent HIV infection.
ART has been extremely effective in treating HIV infection and in increasing survival and quality of life . ART also has promise for preventing HIV transmission through preexposure prophylaxis at an individual level and through the treatment of a critical mass of infected individuals to lower viral load and hence probability of transmission, thus altering transmission dynamics at a population level. Ongoing and planned trials of topical antiretroviral (ARV) gels will advance our understanding of ARVs for prevention. Prevention trials of tenofovir, emtricitabine or a combination of these two drugs will include more than 20 000 persons. Results of efficacy trials are expected in 2010–2012.
We have learned a great deal about how to evaluate new interventions in human clinical trials and how to overcome the frequent methodologic challenges that have resulted in negative outcomes in the previous trials . Site selection and populations with highest incidence rates, rigorous evaluation of interventions, fidelity in delivery of interventions, minimizing design effect and evaluation of trials with HIV endpoints are all important considerations for future trial design.
The use of ARVs in the prevention of mother-to-child HIV transmission (PMTCT) is well established . The challenge in eliminating this mode of transmission lies in our ability to scale-up these programs in the most heavily affected areas, especially Africa. Already weak healthcare delivery systems ill-prepared to provide the most basic care including antenatal care are straining to include HIV testing, administer PMTCT interventions, provide ART for HIV-infected mothers and infants and provide appropriate counseling and support to reduce postpartum transmission. Strengthening of healthcare delivery systems in terms of infrastructure, human resources and supply chain systems in resource-constrained countries is central to realizing the remarkable benefits of PMTCT programs  and better preparing for scale-up of ART access and other known prevention interventions. These investments will have the added advantage of benefiting other health challenges in these setting such as childhood immunization programs, sexual and reproductive health services and tuberculosis (TB) control.
Recent epidemiologic studies have added greatly to our understanding of the importance of sexual and drug-using networks as well as bridging populations impacting HIV transmission . Risk for HIV infection is often more a function of the network one is part of than one's individual behaviors. However, the concurrency of multiple sexual partnerships, especially in settings in which the population level prevalence and incidence rates are high, has been highlighted as a major factor in ongoing high rates of HIV transmission. HIV prevention efforts must account for these critical epidemiologic realities if they are to be effective.
Recent observations have led to an enhanced appreciation for the need for combination HIV prevention programs. Rather than seeking a ‘magic bullet’ to stop HIV, the complex nature of HIV transmission dynamics will likely require the use of all available behavioral, biomedical, structural and societal interventions in concert to limit the spread of HIV. Changing human sexual and drug-using behaviors is often challenging, but is possible . Prevention efforts with HIV-infected persons have been particularly successful. Consequently, there now is wide consensus on the merits of expanding access to HIV testing in order to allow HIV-infected persons to take measures to prevent the onward transmission of the virus and to access care and treatment.
Africa continues to be the epicenter of the HIV pandemic. There have been some encouraging prevention success, but HIV transmission remains at unacceptably high levels in many African nations. Young people, especially girls and young women in Africa, are at particularly high risk for HIV  and despite numerous interventions, including three multilevel randomized control trials with HIV endpoints, we have yet to identify an intervention to reduce HIV infection in adolescents. Addressing risk in young women in these epidemic settings must be at the top of the priority list. Although there have been some advances in behavioral interventions, tackling this problem will require broader societal changes involving men and addressing the underlying gender disparities and power imbalances. A striking feature of the pandemic in this decade is the substantial increase in HIV infection in women, especially in industrialized countries. Thus, advances in preventing HIV infection in these settings will benefit those countries with emerging heterosexually transmitted epidemics such as the USA.
Men who have sex with men (MSM) have played a large part in HIV epidemics in the Western world since AIDS was first identified in 1981 . HIV transmission among MSM remains a challenge in many Western countries and is increasingly being identified as a growing facet of epidemics in Asia and Africa and a potential role of bridging between heterosexual and MSM populations.
Injection drug use (IDU) remains a key driver of HIV transmission in concentrated epidemics in several countries in the West, Eastern Europe and Asia . In Ukraine, HIV transmission among a large population of IDUs and their sexual partners threatens to convert to a generalized epidemic, but it remains to be seen whether heterosexual transmission is sustained apart from IDUs. In many parts of the world, alcohol and non-IDU play a large role in HIV risk behaviors .
Other sexually transmitted infections, especially herpes simplex virus type 2 (HSV-2), contribute synergistically to HIV transmission . Recent pathophysiologic studies have shed light on immune activation and other factors that contribute to enhanced HIV transmission . The HIV epidemic has created a major challenge to the control of TB, the most common serious HIV-related opportunistic infection . Coinfection with HIV and TB is associated with higher mortality rates and there is emerging evidence that ART initiation in these patients could substantially impact mortality rates. The growing TB burden is exacerbated by the substantial growth in multi and extremely drug-resistant TB strains. The integration of HIV and TB care and expansion of HIV testing in TB clinics will impact both the TB and HIV epidemics and outcomes.
The last few years have witnessed an unprecedented global increase in investment to combat the HIV pandemic. Rigorous epidemiologic data and interpretation will be critical in guiding the wisest and most effective use of resources. We must learn from our previous efforts, successful and otherwise, in order to make the greatest impact with future HIV prevention and treatment initiatives.
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2 Diaz T, Garcia-Calleja JM, Ghys PD, Sabin K. Advances and future directions in HIV surveillance in low and middle income countries. Curr Opin HIV AIDS 000–000.
3 Woodman Z, Williamson C. HIV molecular epidemiology: transmission and adaptation to human population. Curr Opin HIV AIDS 000–000.
4 Vermund SH, Allen KL, Abdool Karim Q. HIV prevention science at a crossroads: advances in reducing sexual risk. Curr Opin HIV AIDS 000–000.
5 Gray RH. Methodologies for evaluating HIV prevention intervention (populations and epidemiologic settings). Curr Opin HIV AIDS 000–000.
6 Coovadia JH. Current issues in prevention of mother to child transmission of HIV-1. Curr Opin HIV AIDS 000–000.
7 Rothenberg R. HIV transmission networks. Curr Opin HIV AIDS 000–000.
8 Fisher JD. Examining secondary prevention: the current state of prevention for positives. Curr Opin HIV AIDS 000–000.
9 Cowan F, Pettifor A. HIV in adolescents in sub-Saharan Africa. Curr Opin HIV AIDS 000–000.
10 van Griensven F, de Lind van Wijngaarden JW, Baral S, Grulich A. The global epidemic of HIV infection among men who have sex with men. Curr Opin HIV AIDS 000–000.
11 Des Jarlais D, Arasteh K, Semaan S, Wood E. HIV among injecting drug users: current epidemiology, biologic markers, respondent-driven sampling and supervised injection facilities. Curr Opin HIV AIDS 000–000.
12 Tieu HV, Koblin BA. HIV, alcohol, and noninjection drug users. Curr Opin HIV AIDS 000–000.
13 Tobian AA, Quinn TC. Herpes simplex virus type 2 (HSV-2) and syphilis infections with HIV: an evolving synergy in transmission and prevention. Curr Opin HIV AIDS 000–000.
14 Lawn SD, Churchyard G. Epidemiology of HIV-associated tuberculosis. Curr Opin HIV AIDS 000–000.