Chris Beyrer

Global epidemiology of HIV infection in men who have sex with men

Epidemics of HIV in men who have sex with men (MSM) continue to expand in most countries. We sought to understand the epidemiological drivers of the global epidemic in MSM and why it continues unabated. We did a comprehensive review of available data for HIV prevalence, incidence, risk factors, and the molecular epidemiology of HIV in MSM from 2007 to 2011, and modelled the dynamics of HIV transmission with an agent-based simulation. Our findings show that the high probability of transmission per act through receptive anal intercourse has a central role in explaining the disproportionate disease burden in MSM. HIV can be transmitted through large MSM networks at great speed. Molecular epidemiological data show substantial clustering of HIV infections in MSM networks, and higher rates of dual-variant and multiple-variant HIV infection in MSM than in heterosexual people in the same populations. Prevention strategies that lower biological transmission and acquisition risks, such as approaches based on antiretrovirals, offer promise for controlling the expanding epidemic in MSM, but their potential effectiveness is limited by structural factors that contribute to low health-seeking behaviours in populations of MSM in many parts of the world.

Elevated Risk for HIV Infection among Men Who Have Sex with Men in Low- and Middle-Income Countries 2000–2006: A Systematic Review

Background Recent reports of high HIV infection rates among men who have sex with men (MSM) from Asia, Africa, Latin America, and the former Soviet Union (FSU) suggest high levels of HIV transmission among MSM in low- and middle-income countries. To investigate the global epidemic of HIV among MSM and the relationship of MSM outbreaks to general populations, we conducted a comprehensive review of HIV studies among MSM in low- and middle-income countries and performed a meta-analysis of reported MSM and reproductive-age adult HIV prevalence data. Methods and Findings A comprehensive review of the literature was conducted using systematic methodology. Data regarding HIV prevalence and total sample size was sequestered from each of the studies that met inclusion criteria and aggregate values for each country were calculated. Pooled odds ratio (OR) estimates were stratified by factors including HIV prevalence of the country, Joint United Nations Programme on HIV/AIDS (UNAIDS)–classified level of HIV epidemic, geographic region, and whether or not injection drug users (IDUs) played a significant role in given epidemic. Pooled ORs were stratified by prevalence level; very low-prevalence countries had an overall MSM OR of 58.4 (95% CI 56.3–60.6); low-prevalence countries, 14.4 (95% CI 13.8–14.9); and medium- to high-prevalence countries, 9.6 (95% CI 9.0–10.2). Significant differences in ORs for HIV infection among MSM in were seen when comparing low- and middle-income countries; low-income countries had an OR of 7.8 (95% CI 7.2–8.4), whereas middle-income countries had an OR of 23.4 (95% CI 22.8–24.0). Stratifying the pooled ORs by whether the country had a substantial component of IDU spread resulted in an OR of 12.8 (95% CI 12.3–13.4) in countries where IDU transmission was prevalent, and 24.4 (95% CI 23.7–25.2) where it was not. By region, the OR for MSM in the Americas was 33.3 (95% CI 32.3–34.2); 18.7 (95% CI 17.7–19.7) for Asia; 3.8 (95% CI 3.3–4.3) for Africa; and 1.3 (95% CI 1.1–1.6) for the low- and middle-income countries of Europe. Conclusions MSM have a markedly greater risk of being infected with HIV compared with general population samples from low- and middle-income countries in the Americas, Asia, and Africa. ORs for HIV infection in MSM are elevated across prevalence levels by country and decrease as general population prevalence increases, but remain 9-fold higher in medium–high prevalence settings. MSM from low- and middle-income countries are in urgent need of prevention and care, and appear to be both understudied and underserved.

Burden of HIV among female sex workers in low-income and middle-income countries: a systematic review and meta-analysis

BACKGROUND Female sex workers are a population who are at heightened risk of HIV infection secondary to biological, behavioural, and structural risk factors. However, three decades into the HIV pandemic, understanding of the burden of HIV among these women remains limited. We aimed to assess the burden of HIV in this population compared with that of other women of reproductive age. METHODS We searched PubMed, Embase, Global Health, SCOPUS, PsycINFO, Sociological Abstracts, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Web of Science, and POPLine for studies of female sex workers in low-income and middle-income countries published between Jan 1, 2007, and June 25, 2011. Studies of any design that measured the prevalence or incidence of HIV among female sex workers, even if sex workers were not the main focus of the study, were included. Meta-analyses were done with the Mantel-Haenszel method with a random-effects model characterising an odds ratio for the prevalence of HIV among female sex workers compared with that for all women of reproductive age. FINDINGS Of 434 selected articles and surveillance reports, 102 were included in the analyses, representing 99,878 female sex workers in 50 countries. The overall HIV prevalence was 11·8% (95% CI 11·6-12·0) with a pooled odds ratio for HIV infection of 13·5 (95% CI 10·0-18·1) with wide intraregional ranges in the pooled HIV prevalence and odds ratios for HIV infection. In 26 countries with medium and high background HIV prevalence, 30·7% (95% CI 30·2-31·3; 8627 of 28,075) of sex workers were HIV-positive and the odds ratio for infection was 11·6 (95% CI 9·1-14·8). INTERPRETATION Although data characterising HIV risk among female sex workers is scarce, the burden of disease is disproportionately high. These data suggest an urgent need to scale up access to quality HIV prevention programmes. Considerations of the legal and policy environments in which sex workers operate and actions to address the important role of stigma, discrimination, and violence targeting female sex workers is needed. FUNDING The World Bank, UN Population Fund.

Worldwide burden of HIV in transgender women: a systematic review and meta-analysis

BACKGROUND Previous systematic reviews have identified a high prevalence of HIV infection in transgender women in the USA and in those who sell sex (compared with both female and male sex workers). However, little is known about the burden of HIV infection in transgender women worldwide. We aimed to better assess the relative HIV burden in all transgender women worldwide. METHODS We did a systematic review and meta-analysis of studies that assessed HIV infection burdens in transgender women that were published between Jan 1, 2000, and Nov 30, 2011. Meta-analysis was completed with the Mantel-Haenszel method, and random-effects modelling was used to compare HIV burdens in transgender women with that in adults in the countries for which data were available. FINDINGS Data were only available for countries with male-predominant HIV epidemics, which included the USA, six Asia-Pacific countries, five in Latin America, and three in Europe. The pooled HIV prevalence was 19·1% (95% CI 17·4-20·7) in 11 066 transgender women worldwide. In 7197 transgender women sampled in ten low-income and middle-income countries, HIV prevalence was 17·7% (95% CI 15·6-19·8). In 3869 transgender women sampled in five high-income countries, HIV prevalence was 21·6% (95% CI 18·8-24·3). The odds ratio for being infected with HIV in transgender women compared with all adults of reproductive age across the 15 countries was 48·8 (95% CI 21·2-76·3) and did not differ for those in low-income and middle-income countries compared with those in high-income countries. INTERPRETATION Our findings suggest that transgender women are a very high burden population for HIV and are in urgent need of prevention, treatment, and care services. The meta-analysis showed remarkable consistency and severity of the HIV disease burden among transgender women. FUNDING Center for AIDS Research at Johns Hopkins and the Center for Public Health and Human Rights at the JHU Bloomberg School of Public Health.

Changes in Sexual Behavior and a Decline in HIV Infection among Young Men in Thailand

BACKGROUND In Thailand the epidemic of human immunodeficiency virus (HIV) infection is of recent origin. Because of the high seroprevalence of HIV among sex workers, the Ministry of Public Health began a program in 1990 and 1991 to promote the use of condoms during commercial sex. We evaluated the effect of this and other programs to prevent HIV infection in Thailand. METHODS Using direct interviews, we studied five cohorts of 21-year-old men from northern Thailand who were conscripted into the army by a lottery in 1991, 1993, and 1995. In all, 4311 men were tested for HIV antibodies by enzyme-linked immunosorbent assay, with confirmation by Western blot assay. RESULTS In the 1991 and 1993 cohorts, the prevalence of HIV infection was 10.4 to 12.5 percent. In 1995, it fell to 6.7 percent (P < 0.001). The seroprevalence was only 0.7 percent among men who did not have sexual relations with a sex worker before 1992. Over the study period, the proportion of men who reported having sexual relations with a sex worker fell from 81.4 percent to 63.8 percent (P < 0.001). From 1991 to 1995, the mens reported use of condoms during the most recent sexual contacts with sex workers increased from 61.0 percent to 92.5 percent (P < 0.001); and in 1995, 15.2 percent of men had a history of a sexually transmitted disease, as compared with 42.2 percent in 1991 (P < 0.001). CONCLUSIONS Public health programs in Thailand have led to substantial changes in sexual behavior among young men, especially an increased use of condoms, and the rate of new HIV infections has declined.

Overland heroin trafficking routes and HIV-1 spread in south and south-east Asia

ObjectivesBurma produces approximately 60% of the worlds heroin, Laos is the third leading producer. Recent outbreaks of injecting drug use and HIV-1 in Burma, India, China, and Vietnam have been associated with Burmese and Laotian overland heroin trafficking routes. We analyzed findings from narcotics investigations, molecular epidemiology studies of HIV-1, and epidemiologic and behavioral studies of injecting drug use, to evaluate the roles that the heroin export routes play in the spread of drug use and HIV-1 in south and south-east Asia. MethodsWe reviewed the medical and narcotics literature, the molecular epidemiology of HIV, and did key informant interviews in India, China, and Burma with injecting drug users, drug traffickers, public health staff, and narcotics control personnel. ResultsFour recent outbreaks of HIV-1 among injecting drug users appear linked to trafficking routes. Route 1: From Burmas eastern border to Chinas Yunnan Province, with initial spread of HIV-1 subtype B, and later C. Route 2: Eastern Burma to Yunnan, going north and west, to Xinjiang Province, with B, C, and a B/C recombinant subtype. Route 3: Burma and Laos, through northern Vietnam, to Chinas Guangxi Province, subtype E. Route 4: Western Burma, across the Burma–India border to Manipur, predominant subtype C, and B and E. ConclusionsOverland heroin export routes have been associated with dual epidemics of injecting drug use and HIV infection in three Asian countries and along four routes. Molecular epidemiology is useful for mapping heroin routes. Single country narcotics and HIV programs are unlikely to succeed unless the regional narcotic-based economy is addressed.

Safeguarding human health in the Anthropocene epoch: report of The Rockefeller Foundation-Lancet Commission on planetary health

Earths natural systems represent a growing threat to human health. And yet, global health has mainly improved as these changes have gathered pace. What is the explanation? As a Commission, we are deeply concerned that the explanation is straightforward and sobering: we have been mortgaging the health of future generations to realise economic and development gains in the present. By unsustainably exploiting natures resources, human civilisation has fl ourished but now risks substantial health eff ects from the degradation of natures life support systems in the future. Health eff ects from changes to the environment including climatic change, ocean acidifi cation, land degradation, water scarcity, overexploitation of fi sheries, and biodiversity loss pose serious challenges to the global health gains of the past several decades and are likely to become increasingly dominant during the second half of this century and beyond. These striking trends are driven by highly inequitable, ineffi cient, and unsustainable patterns of resource consumption and technological development, together with population growth. We identify three categories of challenges that have to be addressed to maintain and enhance human health in the face of increasingly harmful environmental trends. Firstly, conceptual and empathy failures (imagination challenges), such as an over-reliance on gross domestic product as a measure of human progress, the failure to account for future health and environmental harms over present day gains, and the disproportionate eff ect of those harms on the poor and those in developing nations. Secondly, knowledge failures (research and information challenges), such as failure to address social and environmental drivers of ill health, a historical scarcity of transdisciplinary research and funding, together with an unwillingness or inability to deal with uncertainty within decision making frameworks. Thirdly, implementation failures (governance challenges), such as how governments and institutions delay recognition and responses to threats, especially when faced with uncertainties, pooled common resources, and time lags between action and eff ect. Although better evidence is needed to underpin appropriate policies than is available at present, this should not be used as an excuse for inaction. Substantial potential exists to link action to reduce environmental damage with improved health outcomes for nations at all levels of economic development. This Commission identifi es opportunities for action by six key constituencies: health professionals, research funders and the academic community, the UN and Bretton Woods bodies, governments, investors and corporate reporting bodies, and civil society organisations. Depreciation of natural capital and natures subsidy should be accounted for so that economy and nature are not falsely separated. Policies should balance social progress, environmental sustainability, and the economy. To support a world population of 9-10 billion people or more, resilient food and agricultural systems are needed to address both undernutrition and overnutrition, reduce waste, diversify diets, and minimise environmental damage. Meeting the need for modern family planning can improve health in the short termeg, from reduced maternal mortality and reduced pressures on the environment and on infrastructure. Planetary health off ers an unprecedented opportunity for advocacy of global and national reforms of taxes and subsidies for many sectors of the economy, including energy, agriculture, water, fi sheries, and health. Regional trade treaties should act to further incorporate the protection of health in the near and long term. Several essential steps need to be taken to transform the economy to support planetary health. These steps include a reduction of waste through the creation of products that are more durable and require less energy and materials to manufacture than those often produced at present; the incentivisation of recycling, reuse, and repair; and the substitution of hazardous materials with safer alternatives. Despite present limitations, the Sustainable Development Goals provide a great opportunity to integrate health and sustainability through the judicious selection of relevant indicators relevant to human wellbeing, the enabling infrastructure for development, and the supporting natural systems, together with the need for strong governance. The landscape, ecosystems, and the biodiversity they contain can be managed to protect natural systems, and indirectly, reduce human disease risk. Intact and restored ecosystems can contribute to resilience (see panel 1 for glossary of terms used in this report), for example, through improved coastal protection (eg, through wave attenuation) and the ability of fl oodplains and greening of river catchments to protect from river fl ooding events by diverting and holding excess water. The growth in urban populations emphasises the importance of policies to improve health and the urban environment, such as through reduced air pollution, increased physical activity, provision of green space, and urban planning to prevent sprawl and decrease the magnitude of urban heat islands. Transdisciplinary research activities and capacity need substantial and urgent expansion. Present research limitations should not delay action. In situations where technology and knowledge can deliver win-win solutions and co-benefi ts, rapid scale-up can be achieved if researchers move ahead and assess the implementation of potential solutions. Recent scientifi c investments towards understanding non-linear state shifts in ecosystems are very important, but in the absence of improved understanding and predictability of such changes, eff orts to improve resilience for human health and adaptation strategies remain a priority. The creation of integrated surveillance systems that collect rigorous health, socioeconomic, and environmental data for defi ned populations over long time periods can provide early detection of emerging disease outbreaks or changes in nutrition and non-communicable disease burden. The improvement of risk communication to policy makers and the public and the support of policy makers to make evidence-informed decisions can be helped by an increased capacity to do systematic reviews and the provision of rigorous policy briefs. Health professionals have an essential role in the achievement of planetary health: working across sectors to integrate policies that advance health and environmental sustainability, tackling health inequities, reducing the environmental impacts of health systems, and increasing the resilience of health systems and populations to environmental change. Humanity can be stewarded successfully through the 21st century by addressing the unacceptable inequities in health and wealth within the environmental limits of the Earth, but this will require the generation of new knowledge, implementation of wise policies, decisive action, and inspirational leadership.

A recent outbreak of human immunodeficiency virus type 1 infection in Southern China was initiated by two highly homogeneous, geographically separated strains, circulating recombinant form AE and a novel BC recombinant

ABSTRACT New outbreaks of human immunodeficiency virus type 1 (HIV-1) among injecting drug users (IDUs) are spreading in China along heroin trafficking routes. Recently, two separate HIV-1 epidemics among IDUs were reported in Guangxi, Southern China, where partial sequencing of the env gene showed subtype C and circulating recombinant form (CRF) AE. We evaluated five virtually full-length HIV-1 genome sequences from IDUs in Guangxi to determine the genetic diversity and the presence of intersubtype recombinants. Sequence analysis showed two geographically separated, highly homogeneous HIV-1 strains. B/C intersubtype recombinants were found in three IDUs from Baise City, in a mountainous region near the Yunnan-Guangxi border. These were mostly subtype C, with portions of the capsid and reverse transcriptase (RT) genes from subtype B. The subtype B portion of the capsid was located in the N-terminal domain, which has been shown to influence virus core maturation, virus infectivity, and binding to cyclophilin A, whereas the subtype B portion of RT was located in the palm subdomain, which is the active site of the enzyme. These BC recombinants differed from a BC recombinant found in Xinjiang Province in northwestern China. CRF AE strains were found in IDUs from Nanning, the capital of Guangxi, and in IDUs from Pingxiang City near the China-Vietnam border. The AE and BC recombinants were both remarkable for their low interpatient diversity, less than 1% for the full genome. Rapid spread of HIV-1 among IDUs may foster the emergence of highly homogeneous strains, including novel recombinants in regions with multiple subtypes.

The Lancet CommissionsSafeguarding human health in the Anthropocene epoch: report of The Rockefeller Foundation–Lancet Commission on planetary health

Earths natural systems represent a growing threat to human health. And yet, global health has mainly improved as these changes have gathered pace. What is the explanation? As a Commission, we are deeply concerned that the explanation is straightforward and sobering: we have been mortgaging the health of future generations to realise economic and development gains in the present. By unsustainably exploiting natures resources, human civilisation has fl ourished but now risks substantial health eff ects from the degradation of natures life support systems in the future. Health eff ects from changes to the environment including climatic change, ocean acidifi cation, land degradation, water scarcity, overexploitation of fi sheries, and biodiversity loss pose serious challenges to the global health gains of the past several decades and are likely to become increasingly dominant during the second half of this century and beyond. These striking trends are driven by highly inequitable, ineffi cient, and unsustainable patterns of resource consumption and technological development, together with population growth. We identify three categories of challenges that have to be addressed to maintain and enhance human health in the face of increasingly harmful environmental trends. Firstly, conceptual and empathy failures (imagination challenges), such as an over-reliance on gross domestic product as a measure of human progress, the failure to account for future health and environmental harms over present day gains, and the disproportionate eff ect of those harms on the poor and those in developing nations. Secondly, knowledge failures (research and information challenges), such as failure to address social and environmental drivers of ill health, a historical scarcity of transdisciplinary research and funding, together with an unwillingness or inability to deal with uncertainty within decision making frameworks. Thirdly, implementation failures (governance challenges), such as how governments and institutions delay recognition and responses to threats, especially when faced with uncertainties, pooled common resources, and time lags between action and eff ect. Although better evidence is needed to underpin appropriate policies than is available at present, this should not be used as an excuse for inaction. Substantial potential exists to link action to reduce environmental damage with improved health outcomes for nations at all levels of economic development. This Commission identifi es opportunities for action by six key constituencies: health professionals, research funders and the academic community, the UN and Bretton Woods bodies, governments, investors and corporate reporting bodies, and civil society organisations. Depreciation of natural capital and natures subsidy should be accounted for so that economy and nature are not falsely separated. Policies should balance social progress, environmental sustainability, and the economy. To support a world population of 9-10 billion people or more, resilient food and agricultural systems are needed to address both undernutrition and overnutrition, reduce waste, diversify diets, and minimise environmental damage. Meeting the need for modern family planning can improve health in the short termeg, from reduced maternal mortality and reduced pressures on the environment and on infrastructure. Planetary health off ers an unprecedented opportunity for advocacy of global and national reforms of taxes and subsidies for many sectors of the economy, including energy, agriculture, water, fi sheries, and health. Regional trade treaties should act to further incorporate the protection of health in the near and long term. Several essential steps need to be taken to transform the economy to support planetary health. These steps include a reduction of waste through the creation of products that are more durable and require less energy and materials to manufacture than those often produced at present; the incentivisation of recycling, reuse, and repair; and the substitution of hazardous materials with safer alternatives. Despite present limitations, the Sustainable Development Goals provide a great opportunity to integrate health and sustainability through the judicious selection of relevant indicators relevant to human wellbeing, the enabling infrastructure for development, and the supporting natural systems, together with the need for strong governance. The landscape, ecosystems, and the biodiversity they contain can be managed to protect natural systems, and indirectly, reduce human disease risk. Intact and restored ecosystems can contribute to resilience (see panel 1 for glossary of terms used in this report), for example, through improved coastal protection (eg, through wave attenuation) and the ability of fl oodplains and greening of river catchments to protect from river fl ooding events by diverting and holding excess water. The growth in urban populations emphasises the importance of policies to improve health and the urban environment, such as through reduced air pollution, increased physical activity, provision of green space, and urban planning to prevent sprawl and decrease the magnitude of urban heat islands. Transdisciplinary research activities and capacity need substantial and urgent expansion. Present research limitations should not delay action. In situations where technology and knowledge can deliver win-win solutions and co-benefi ts, rapid scale-up can be achieved if researchers move ahead and assess the implementation of potential solutions. Recent scientifi c investments towards understanding non-linear state shifts in ecosystems are very important, but in the absence of improved understanding and predictability of such changes, eff orts to improve resilience for human health and adaptation strategies remain a priority. The creation of integrated surveillance systems that collect rigorous health, socioeconomic, and environmental data for defi ned populations over long time periods can provide early detection of emerging disease outbreaks or changes in nutrition and non-communicable disease burden. The improvement of risk communication to policy makers and the public and the support of policy makers to make evidence-informed decisions can be helped by an increased capacity to do systematic reviews and the provision of rigorous policy briefs. Health professionals have an essential role in the achievement of planetary health: working across sectors to integrate policies that advance health and environmental sustainability, tackling health inequities, reducing the environmental impacts of health systems, and increasing the resilience of health systems and populations to environmental change. Humanity can be stewarded successfully through the 21st century by addressing the unacceptable inequities in health and wealth within the environmental limits of the Earth, but this will require the generation of new knowledge, implementation of wise policies, decisive action, and inspirational leadership.

Modified social ecological model: a tool to guide the assessment of the risks and risk contexts of HIV epidemics

BackgroundSocial and structural factors are now well accepted as determinants of HIV vulnerabilities. These factors are representative of social, economic, organizational and political inequities. Associated with an improved understanding of multiple levels of HIV risk has been the recognition of the need to implement multi-level HIV prevention strategies. Prevention sciences research and programming aiming to decrease HIV incidence requires epidemiologic studies to collect data on multiple levels of risk to inform combination HIV prevention packages.DiscussionProximal individual-level risks, such as sharing injection devices and unprotected penile-vaginal or penile-anal sex, are necessary in mediating HIV acquisition and transmission. However, higher order social and structural-level risks can facilitate or reduce HIV transmission on population levels. Data characterizing these risks is often far more actionable than characterizing individual-level risks. We propose a modified social ecological model (MSEM) to help visualize multi-level domains of HIV infection risks and guide the development of epidemiologic HIV studies. Such a model may inform research in epidemiology and prevention sciences, particularly for key populations including men who have sex with men (MSM), people who inject drugs (PID), and sex workers. The MSEM builds on existing frameworks by examining multi-level risk contexts for HIV infection and situating individual HIV infection risks within wider network, community, and public policy contexts as well as epidemic stage. The utility of the MSEM is demonstrated with case studies of HIV risk among PID and MSM.SummaryThe MSEM is a flexible model for guiding epidemiologic studies among key populations at risk for HIV in diverse sociocultural contexts. Successful HIV prevention strategies for key populations require effective integration of evidence-based biomedical, behavioral, and structural interventions. While the focus of epidemiologic studies has traditionally been on describing individual-level risk factors, the future necessitates comprehensive epidemiologic data characterizing multiple levels of HIV risk.