HIV 2014: Science, Community, and Policy for Key Vulnerable Populations

Journal Articles and Reports

Keynote address: global prevalence of HIV in MSM

Beyrer C, Baral SD, van Griensven F, et al. Global epidemiology of HIV infection in men who have sex with men. Lancet. 2012;380(9839):367-77.

Beyrer C, Sullivan P, Sanchez J, et al. The increase in global HIV epidemics in MSM. AIDS. 2013;27(17):2665-78.

Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363(27):2587-99.

Millett GA, Peterson JL, Flores SA, et al. Comparisons of disparities and risks of HIV infection in black and other men who have sex with men in Canada, UK, and USA: a meta-analysis. Lancet. 2012;380(9839):341-8.

Oster AM, Wejnert C, Mena LA, et al. Network analysis among HIV-infected young black men who have sex with men demonstrates high connectedness around few venues. Sex Transm Dis. 2013;40(3):206-12.

Sullivan PS, Carballo-Diéguez A, Coates T, et al. Successes and challenges of HIV prevention in men who have sex with men. Lancet. 2012;380(9839):388-99.

Discrimination and criminalization in key populations

Amon JJ, Pearshouse R, Cohen JE, Schleifer R. Compulsory drug detention in East and Southeast Asia: Evolving government, UN and donor responses. Int J Drug Policy. 2014;25(1):13-20.

Baral S, Beyrer C, Muessig K, et al. Burden of HIV among female sex workers in low-income and middle-income countries: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12(7):538-49.

Ghoshal N. Human Rights Watch. Treat us like human beings: discrimination against sex workers, sexual and gender minorities, and people who use drugs in Tanzania. 2013.

Todrys KW, Amon JJ, Malembeka G, et al. Imprisoned and imperiled: access to HIV and TB prevention and treatment, and denial of human rights, in Zambian prisons. J Int AIDS Soc. 2011;14:1-11.

Wurth MH, Schleifer R, McLemore M, et al. Condoms as evidence of prostitution in the United States and the criminalization of sex work. J Int AIDS Soc. 2013;16:18626-8.

Obstacles for people who use drugs

Chawla S. United Nations Office on Drugs and Crime. World Drug Report 2013.

Degenhardt L, Mathers BM, Wirtz AL, et al. What has been achieved in HIV prevention, treatment and care for people who inject drugs, 2010-2012? A review of the six highest burden countries. Int J Drug Policy. 2014;1:53-60.

Global Commission on Drug Policy. The war on drugs and HIV/AIDS: how the criminalization of drug use fuels the global pandemic. 2012.

Stimson GV, Cook C, Bridge J, et al. International Harm Reduction Association. Three cents a day is not enough: Resourcing HIV-related Harm: Reduction on a Global Basis. 2010.

World Health Organization, UNODC, UNAIDS. HIV/AIDS: Technical guide for countries to set targets for universal access to HIV prevention, treatment and care for injecting drug users, 2012 revision. 2013.

From effective treatment to prevention

Cowan FM, Mtetwa S, Davey C, et al. Engagement with HIV prevention treatment and care among female sex workers in Zimbabwe: a respondent driven sampling survey. PLoS One. 2013;8(10):e77080.

The South African National AIDS Council. The national strategic plan (NSP) 2012–2016 in a nutshell. 2012.

Pushing the envelope of prevention

Ananworanich J, Schuetz A, Vandergeeten C, et al. Impact of multi-targeted antiretroviral treatment on gut T cell depletion and HIV reservoir seeding during acute HIV infection. PLoS One. 2012;7(3):e33948.

Andrews CD, Spreen WR, Mohri H, et al. Long-acting integrase inhibitor protects macaques from intrarectal simian/human immunodeficiency virus. Science. 2014;343(6175):1151-4.

Archin NM, Vaidya NK, Kuruc JD, et al. Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection. Proc Natl Acad Sci U S A. 2012;109(24):9523-8.

Chun TW, Justement JS, Moir S, et al. Decay of the HIV reservoir in patients receiving antiretroviral therapy for extended periods: implications for eradication of virus. J Infect Dis. 2007;195(12):1762-4.

Siliciano JD, Kajdas J, Finzi D, et al. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med. 2003;9(6):727-8.

Treating HIV coinfections and comorbidities

Abed Al-Darraji HA, Abd Razak H, Ng KP, et al. The diagnostic performance of a single GeneXpert MTB/RIF assay in an intensified tuberculosis case finding survey among HIV-infected prisoners in Malaysia. PLoS One. 2013;8(9):e73717.

Al-Darraji HA, Kamarulzaman A, Altice FL. Isoniazid preventive therapy in correctional facilities: a systematic review. Int J Tuberc Lung Dis. 2012;16(7):871-9.

Azbel L, Wickersham JA, Grishaev Y, et al. Burden of infectious diseases, substance use disorders, and mental illness among Ukrainian prisoners transitioning to the community. PLoS One. 2013;8(3):e59643.

Deeks SG, Tracy R, Douek DC. Systemic effects of inflammation on health during chronic HIV infection. Immunity. 2013;39(4):633-45.

Freiberg MS, Chang CC, Kuller LH, et al. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med. 2013;173(8):614-22.

Grebely J, Dore GJ. Can hepatitis C virus infection be eradicated in people who inject drugs? Antiviral Res. 2014;104:62-72.

Hunt PW. HIV and inflammation: mechanisms and consequences. Curr HIV/AIDS Rep. 2012;9(2):139-47.

Margolis B, Al-Darraji HA, Wickersham JA, et al. Prevalence of tuberculosis symptoms and latent tuberculous infection among prisoners in northeastern Malaysia. Int J Tuberc Lung Dis. 2013;17(12):1538-44.

Morozova O, Dvoryak S, Altice FL. Methadone treatment improves tuberculosis treatment among hospitalized opioid dependent patients in Ukraine. Int J Drug Policy. 2013;24(6):e91-8.

Post WS, Budoff M, Kingsley L, et al. Associations between HIV infection and subclinical coronary atherosclerosis. Ann Intern Med. 2014;160(7):458-67.

Sponsors

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Note: The HIV 2014: Science, Community and Policy for Key Vulnerable Populations symposium was cosponsored by the Joint United Nations Programme on HIV/AIDS (UNAIDS). The views expressed in symposium materials or publications, by speakers and moderators, or by any symposium cosponsors do not necessarily reflect the official views or policies of UNAIDS; nor does mention of trade names, commercial practices, or organizations imply endorsement by UNAIDS.

The Microbiology & Infectious Diseases Discussion Group is proudly supported by

The rate of new HIV infections has been falling over the last 10 years in many parts of the world. HIV prevalence is still climbing, but this trend could indicate, optimistically, that more people are living longer on antiretroviral therapy (ART). UNAIDS estimates 35 million people are living with HIV. For the first time, scientists and stakeholders are discussing the end of AIDS, through prevention and treatment—a goal that would not have been discussed a few years ago. The UNAIDS vision of zero new HIV infections, zero AIDS-related deaths, and zero discrimination was the topic of the Academy's 2013 HIV symposium, The Three Zeros of Eliminating HIV/AIDS: Global Science and Policy.

As the world moves toward preventing and curing HIV, however, key vulnerable populations, including men who have sex with men (MSM), transgender people, sex workers (SW), and people who inject drugs (PWID), do not have access to basic HIV care. These key populations are identified by a higher burden of HIV infection and lower rate of accessing HIV care and services compared to the general population and by widespread social and legal discrimination. The HIV continuum of care involves a progression from HIV testing and diagnosis to health care coverage, ART access and adherence, reduced CD4⁺ T cell count, and finally suppression of viral load. Often these neglected groups have lower rates of achieving all the steps in the continuum.

The HIV 2014 symposium convened policy makers, community representatives, and activists to discuss how to improve HIV care for key populations. A first step is to understand where vulnerable people are located. For MSM, the answer is everywhere. In all countries with good data, MSM have higher prevalence and incidence of HIV. But the factors associated with HIV risk in MSM differ between countries, so it is important to study and consider regional context. HIV prevalence among PWID is particularly high in the U.S., Eastern Europe, Russia, East Africa, and Southeast Asia, although many countries lack data. Data describing HIV prevalence among sex workers are also scant but consistently show rates that are manyfold higher than those in the background population.

Another question is why key populations are underserved. It is becoming clear based on reports from Africa, Asia, and the U.S. that stigma and discrimination from police and health care workers, as well as criminalization and human rights violations, ostracize vulnerable people from HIV care. Pilot programs in Eastern Europe and sub-Saharan Africa providing dignified care to these populations have made strides in improving HIV diagnosis and treatment. These programs also allow researchers to evaluate the use of ART for HIV prevention, a strategy known as pre-exposure prophylaxis (PrEP) that is known to be effective. However, political and funding pressures have stifled the efforts of several such programs.

In his opening remarks, Luiz Loures of UNAIDS identified current efforts to improve HIV prevention and care among key populations as the fourth phase of the HIV response. The first was marked by an initial reaction to the epidemic. The next involved organizing scientists and policy makers. The third, at the turn of the century, brought a commitment from many countries to provide resources for responding to AIDS and the establishment of the Global Fund to Fight AIDS, Tuberculosis and Malaria.

In this fourth phase, Loures asserted, the tools are available to end the AIDS epidemic; the challenge now is unequal access to HIV prevention, care, and treatment. For example, adults have better access than children and PWID in Russia are less likely than any other population in that country to receive preventive services and treatments. At the 2014 International AIDS Conference in Melbourne, Australia, UNAIDS will release a report that will define the reasons for these gaps and identify actions that should be taken; however, Loures pointed out that the available data are very weak and much more evidence-based direction is needed.

Low- and middle-income MSM are less likely than high-income MSM to access HIV testing and treatment. (Image courtesy of Luiz Loures)

Highlights

MSM, SW, and PWID have a disproportionately high global burden of HIV.

The prevalence and incidence of HIV are much higher among MSM than in the general adult population.

Structural risks, including criminalization, discrimination, and abuse by health care and law enforcement professionals, contribute to the high HIV burden in key populations.

Although interventions such as PrEP and needle syringe programs are effective, structural risks need to be reduced so that key populations can access services.

Keynote address: global prevalence of HIV in MSM

In his keynote address, Chris Beyrer of Johns Hopkins Bloomberg School of Public Health presented grim statistics on the global burden of HIV among MSM. MSM are facing an HIV epidemic, but questions remain about why this population is vulnerable and how it accesses the HIV continuum of care.

These data and questions were recently explored in a special issue of The Lancet. In one article, Beyrer and colleagues reported that HIV prevalence in MSM has soared above that found in the general adult population in 10 regions of the world. The trend is particularly stark in sub-Saharan Africa. However, data on HIV prevalence in MSM are not available for many countries, especially in Africa and the Middle East. A 2013 study by Beyrer and colleagues found that new HIV infections are also increasing among MSM in countries for which data are available, such as the U.S., China, and Thailand. This increase contrasts the trend in other populations, in which HIV incidence "happily is either flat or declining," Beyrer said. In the U.S. in 2010, 64% of HIV diagnoses among adults and adolescents were among MSM, according to Centers for Disease Control and Prevention (CDC) data.

HIV prevalence in MSM is higher than in the general adult population in 10 global regions, 2007–2011. (Image courtesy of Chris Beyrer)

Although risk in MSM is affected by individual-level factors, such as engaging in unprotected anal sex with multiple partners, these factors do not fully explain the higher risk for HIV in the MSM population. Studies show that network-level factors also play a part; large, poorly connected social networks are associated with increased HIV risk. Understanding how gay men connect with each other will inform prevention and treatment efforts. A recent CDC survey of a small group of young black MSM with HIV in Mississippi found that most of the men met their sexual partners in bars or at a college.

Researchers have also made headway in understanding how MSM access the HIV continuum of care. One of the first investigations of its kind found that black MSM in the U.S., the UK, and Canada were 2.6 times more likely than other MSM to be diagnosed with HIV. Yet they were half as likely to have health insurance and half as likely to receive ART, and therefore half as likely to have full viral suppression. In a study in Moscow, Beyrer recently found that only 20% of HIV-positive MSM knew their HIV status and 9% were taking ART. The requirement at most clinics to report name and sexual status was a commonly cited reason for avoiding HIV testing centers. In response to the need for services, Beyrer and colleagues set up a clinic in Moscow to provide anonymous testing and treatment, but it has closed in the wake of Russian laws against homosexual propaganda.

Ending his talk on a positive note, Beyrer discussed the medical interventions already available to reduce HIV risk in MSM. For men at high risk of becoming infected through unprotected anal sex there are effective interventions such as PrEP, as demonstrated in 2010 by a groundbreaking study in the New England Journal of Medicine. Condom use and counseling could also be effective. The PARTNER study, presented at the 2014 International Antiviral Society–USA Conference on Retroviruses and Opportunistic Infections (CROI), has provided good, though preliminary, evidence that providing HIV-positive MSM with ART reduces transmission to sexual partners. However, as Beyrer noted, these medical interventions require safe, dignified, and humane settings for implementation.

Black MSM are less likely than white MSM to access the HIV continuum of care. (Image courtesy of Chris Beyrer)

Discrimination and criminalization of key populations

It is becoming increasingly clear that structural risks contribute to the higher HIV burden in MSM, in addition to individual-level and network risks. These structural risks arise from discrimination against HIV-positive populations in law enforcement and health care settings and from criminalization of homosexuality.

Joe Amon of Human Rights Watch advocated for the study of these risks in the field of political epidemiology, which examines how laws and policies affect health. Amon has applied political epidemiology to study HIV risk and inadequate access to treatment among MSM and other key populations. For a report published last year, he and his colleagues spoke with MSM, people who use drugs, and other vulnerable individuals in Tanzania about abuse, assault, and rape by police. In another study, prisoners in Zambia reported lacking access to HIV testing and ART and experiencing sexual abuse while waiting to see a judge. These types of findings have already spurred action against human rights violations. In the discussion following the session, Amon explained that UNAIDS has strongly criticized forced drug detention centers in Cambodia, Vietnam, China, and other Asian countries, where individuals face abuse and forced labor as a purported strategy for ending drug addiction. Centers in Cambodia were closed in response.

This session also focused on the global HIV burden among sex workers and the obstacles to reducing that burden. Sex workers in U.S. cities report being harassed by police and arrested for attempted solicitation as a result of carrying condoms. Although judges often throw out these charges, the result is that sex workers carry fewer condoms and have more unprotected sex for fear of police abuse, Amon reported.

Police profiling and stop-and-frisk policies lead to sex workers in U.S. cities carrying fewer condoms and having more unprotected sex. (Image courtesy of Joe Amon)

Anna-Louise Crago of the University of Toronto explained the factors that contribute to huge HIV and health risks among sex workers. Criminalization of sex work is becoming more common. Imprisonment often limits SW access to preventive services, care, and ART and is associated with HIV status in many parts of the world. In addition, repression by police often leads to displacement of SW to remote and dangerous areas. Abuse and discrimination by health care workers inhibits SW access to ART, as seen in studies in sub-Saharan Africa and Asia. There is also discrimination at the funding level: Crago reported that only a tiny fraction of global funds go to preventing HIV in sex workers, and some of these funds are directed to detention centers that are not evidence-based. These issues will be the focus of an upcoming special issue of The Lancet.

Missed opportunities for drug users

Daniel Raymond from Harm Reduction Coalition opened his talk with a look at statistics describing people who inject drugs (PWID). Although the United Nations Office on Drugs and Crime (UNODC) estimates there are 14 million PWID globally, prevalence data are poor for many countries in Africa, the Middle East, and South America. Areas where injection drug use has traditionally been high include Eastern Europe and Central and Southeast Asia, but there is also new concern in Southern Africa and South Asia, where heroin trafficking has expanded. An estimated 1.6 million PWID are HIV-positive.

In 2013 the WHO, UNODC, and UNAIDS published a guide featuring nine strategies for preventing HIV in PWID. Raymond's talk focused on three: needle and syringe programs (NSPs), opioid substitution therapy (OST), and ART. Raymond suggested that programs combining these strategies could have the greatest impact on the HIV epidemic in PWID. A recent study in the six countries that contribute half the worldwide PWID population—China, Malaysia, Russia, Ukraine, Vietnam, and the U.S.—reveals that with the exception of Vietnam the countries fall far short of providing the target 200 syringes per PWID per year. According to amfAR data, most clinics in the U.S. providing syringe exchange programs are clustered on the East and West Coasts and in the northern part of the Midwest, and many clinics deliver low volumes of syringes. The study also found that only a small percentage of PWID are receiving OST in the six countries and similarly low rates of HIV-positive PWID are receiving ART.

Scaling up these interventions will require increased funding and legal changes, Raymond noted. Data suggest there is very little funding dedicated to PWID; most funding comes from international donors, but it has not kept pace with need. The Law Enforcement and Harm Reduction Network has created a global coalition of law enforcement agencies and officers aiming to reduce antagonism by police and in legal settings toward key populations. The goal is to help PWID feel less apprehensive about accessing services such as NSPs.

Most of the needle syringe programs in the U.S. are geographically clustered, leaving many regions without access. (Image courtesy of Daniel Raymond)

Highlights

There is a global shift toward prevention with a focus on key populations, as exemplified by South Africa's new HIV strategies.

In Zimbabwe, the establishment of centers offering medical and legal services to sex workers has led to the first trial testing antiretroviral treatment as prevention in sex workers.

Early treatment could reduce the extent of latently infected T cells. New cohort studies of MSM are looking into whether early treatment during acute infection could prevent chronic infection.

The drug GSK744 LA is in phase II studies and could become a new PrEP agent that only requires quarterly injections.

From effective treatment to prevention

The session devoted to new HIV prevention strategies kicked off with a presentation by Fareed Abdullah of the South African National AIDS Council. Abdullah spoke about how the successful expansion of ART treatment programs encouraged the country to adopt prevention as a priority. Of the estimated 6.4 million South Africans living with HIV, there are 1.9 million taking ART, constituting one of the largest treatment groups in the world. South Africa, along with many other countries and organizations including UNAIDS, is now focused on HIV prevention and on key populations. Programs provide early treatment and education and efforts are underway to reduce human rights violations.

Abdullah explained that South Africa is well positioned to reach key populations, based on its progressive politics and generally tolerant culture. Sex workers face a particularly high burden of HIV in South Africa, but the country emphasizes dignity and equality in handling their cases; Abdullah noted it has made a point of addressing legal and human rights abuses, although police harassment and violence still exist.

HIV prevalence is higher among young women than among young men in South Africa, suggesting young women are infected by older men. (Image courtesy of Fareed Abdullah)

The National AIDS Council's National Strategic Plan is creating policies and programs for SW, MSM, and PWID, a smaller key population in South Africa. In one program largely supported by the Global Fund, the National AIDS Council will work with community-based organizations to reach 33 600 sex workers, 100 000 MSM, and 140 000 inmates in all 250 prisons. There are also government-funded programs that provide services to SW, MSM, and for the first time, PWID, across South Africa.

Government-funded programs for SW, MSM, and PWID are distributed across South Africa. (Image courtesy of Fareed Abdullah)

The potential use of ART as a prevention strategy is being investigated in the SAPPH-Ire trial in Zimbabwe, the first trial to look at treatment as prevention in female SW. Frances Cowan of the Centre for Sexual Health and HIV/AIDS Research Zimbabwe described the trial, which grew out of the Sisters with a Voice program begun in 2009 as part of the National AIDS Council of Zimbabwe. Sisters with a Voice provides SW with HIV testing, clinical care, condoms, counseling, and legal advice. Nearly 15 000 women have accessed services at the now 36 sites. The scale of the program prompted stakeholders to realize the opportunity to collect information about SW in Zimbabwe, a population for which data were scarce. A survey published last year covering 3 sites revealed that 50%–70% of women were HIV-positive but only half knew their status and 30%–40% were taking ART. Women reported fear of arrest and humiliation and lack of anonymity as reasons for avoiding health care.

These findings motivated researchers to initiate the SAPPH-Ire trial, conducted at 14 sites assigned to either intervention or control groups. The aim of the intervention is to reduce the number of SW in Zimbabwe with detectable levels of HIV, either by preventing infections or by reducing viral load via ART. The trial compares standard care to the SAPPH-Ire intervention, which includes access to PrEP for women who test HIV-negative and access to ART for women who test HIV-positive. Phone and text messages remind women in the intervention group about appointments and drug therapy. Preliminary baseline data at the trial outset suggest that the number of women accessing HIV services is improving overall. In about 18 months, the researchers will conduct surveys to determine the effectiveness of the intervention.

Survey of female SW at three program sites in Zimbabwe. Between 50% and 70% of women were HIV-positive but only half knew their status. (Image courtesy of Frances Cowan)

Pushing the envelope on prevention

In the first few days after HIV infection, the acute infection stage, it may be possible to clear the virus. A 2007 study associated ART initiation within the first few months of infection, after the acute stage, with a much shorter half-life of latently infected CD4⁺ T cells than is seen when treatment begins during chronic infection, raising the possibility of eradicating virus from these latent viral reservoirs. To study the effects of ART initiation during acute infection, Jerome Kim of Walter Reed Army Institute of Research and colleagues followed key populations that have high rates of new HIV infection. The unanswered question is whether it is possible to initiate treatment early enough to prevent chronic infection.

The first cohort, RV 217, includes female SW in Uganda, Kenya, and Tanzania and MSM and transgender individuals in Thailand. Twice a week, the participants donate a small volume of blood via finger stick for nucleic acid-based HIV testing, to allow researchers to quickly detect new infections; since the trial began in 2009, almost 2000 people have enrolled and 99 have become infected. The second cohort, RV 254, has enrolled 158 acutely infected individuals, mostly MSM, in Bangkok, Thailand. The participants are undergoing invasive tests—including colon, gut, and lymph node biopsy and lumbar puncture to obtain cerebrospinal fluid—so that researchers can identify where reservoirs of HIV-infected cells are established early in infection. Kim said his team is close to beginning studies that will assess whether early treatment to contain the viral reservoir could lead to a functional cure.

In preliminary studies in monkeys, initiating ART 3 days after infection did not prevent HIV from rebounding after a 6-month treatment course. However, early initiation was associated with lower viral load in the lymph nodes, suggesting there could be a shift in reservoirs with early treatment.

Results from a subset of the RV 217 cohort suggest that the peak viral load, and time to peak viral load, contribute to the subsequent course of infection. (Image courtesy of Jerome Kim)

Chasity Andrews of Aaron Diamond AIDS Research Center talked about a new long-acting injectable drug, GSK744 long-acting (GSK744 LA), which entered phase II human safety studies in April 2014. GSK744 LA could provide an alternative to available PrEP therapy, which requires taking a daily pill containing tenofovir and emtricitabine for effective prevention of HIV. GSK744 LA, derived from dolutegravir, an HIV integrase inhibitor recently approved by the FDA, instead can be prepared as an intramuscular injectable nanosuspension that is maintained in the plasma at an effective dose for 16 weeks.

Pharmacokinetic data from a phase I trial of GSK744 LA demonstrated that healthy volunteers maintain effective drug levels in their plasma for 16 weeks after a single intramuscular injection. (Image courtesy of Chasity Andrews)

Andrews presented data published recently in Science on GSK744 LA as prevention in rhesus macaques. At low doses, the drug protected macaques from repeated intrarectal exposure to simian HIV with 100% efficacy. Unpublished experiments by CDC researchers presented at the 2014 CROI meeting suggest GSK744 LA prevents infection in pigtail macaques following vaginal exposure. Discussing the possibility of the development of resistance to GSK744 LA, Andrews reported that none has been observed in her team's animal experiments.

In preclinical animal studies, a single dose of GSK744 LA protected rhesus macaques from 5 to 10 intrarectal challenges of simian HIV. (Image courtesy of Chasity Andrews)

Highlights

A new generation of hepatitis C antivirals has dramatically improved care and could be more effective than current HCV treatments in people coinfected with HIV.

There is growing interest in understanding whether HIV disease and antiretroviral treatment increase the risk of age-related conditions.

HIV and tuberculosis coinfection presents a serious health risk among prisoners.

A harm reduction program in Ukraine has made strides in reaching young people who use drugs but faces serious obstacles.

Treating HIV coinfections and comorbidities

Although HIV infection often complicates the treatment of other diseases, many challenges associated with treating hepatitis C virus (HCV) in the context of HIV could now be in the past. The newest generation of HCV antivirals, simeprevir and sofosbuvir, can cure HCV infections at rates of 90% or higher in 12–48 weeks, compared with older interferon-based strategies that were only 40% effective and entailed months of treatment and difficult side effects. Furthermore, unlike interferon-based strategies, new HCV antivirals appear to work just as well in people coinfected with HIV as in people not coinfected with HIV. "It is an exciting time to be treating people with hepatitis C," said Kristen Marks of Weill Cornell Medical College.

Nevertheless, only a small percentage of people infected with HCV receive adequate care. In the U.S. only 25% of those living with chronic HCV know they are infected and among those diagnosed only 5% receives interferon-based therapy. These numbers could be improving now that less-toxic and more-effective treatments are available, partly because doctors are more willing to treat patients. The low rate of diagnosis could improve with recent recommendations to test baby boomers, who make up 75% of the undiagnosed. There is a high burden of HCV infection in MSM, who account for most new HCV infections. Guidelines suggest offering HCV screening to MSM who are living with HIV, because of the high HCV incidence in this population. Marks suggested that as HCV treatment becomes easier to manage, patients may be able to see a primary care doctor instead of a specialist or receive treatment at needle syringe programs.

The new generation of HCV antivirals appear to be just as effective in people coinfected with HIV. (Image courtesy of Kristen Marks)

Looking more generally at the relationship between HIV and comorbidities, there is mounting interest in whether HIV infection affects the aging process. Steven Deeks of the University of California, San Francisco, explained that tackling this question is less about asking whether HIV leads to higher rates of heart disease and cancer, although there is evidence for both, than it is about measuring how well patients function and, perhaps more importantly as a metric for aging, recover from illness. Studies, including one by Deeks and his colleagues, suggest that changes in function and resilience, collectively known as geriatric syndromes, are associated with HIV infection, even among those on antiretroviral treatment.

Reasons abound to explain why HIV infection and ART could lead to clinical signs of aging: HIV is associated with elevated inflammation due to viral replication and coinfection, which is in turn associated with heart disease; many patients need multiple medications, some toxic to the liver and kidneys; and people living with HIV could feel socially isolated, especially, Deeks pointed out, patients who are survivors of the 1980s HIV epidemic. Early antiretroviral treatment is the most important strategy to mitigate signs of aging; Deeks estimates early ART solves 90% of the problem by reducing inflammation, the major driver of aging. He recommends that his patients improve their support network and diet, exercise frequently, cease smoking, and treat coinfections.

HIV infection could affect many health factors, including inflammation and liver function, which in turn influence aging. (Image courtesy of Steven Deeks)

There is no question that HIV negatively affects tuberculosis infection. A patient with latent TB has a 10% lifetime risk of developing the disease, but the risk jumps to 10% per year with HIV coinfection. As Frederick Altice of Yale School of Medicine explained, there is a high risk of TB and HIV coinfection in prisons and criminal justice systems around the world because of the high prevalence of both diseases (particularly multidrug-resistant TB) and factors such as poor ventilation, crowding, and malnutrition.

Altice discussed the Malaysian prison system as a case study of a high-risk, incubating environment. In this setting, there is mandatory screening for HIV, but not for TB, and TB is the leading cause of prisoner death. An intervention that screened for TB using evidence-based methods such as sputum microscopy or Gene Xpert reduced TB incidence and mortality. However reducing TB transmission in the criminal justice system will require better TB screening, possibly combined with the anti-TB drug isoniazid, along with HIV screening, ART access, and structural changes such as incarceration alternatives, Altice noted.

Screening for TB using sputum microscopy or Gene Xpert can reduce TB mortality in prisons. (Image courtesy of Frederick Altice)

Accessing hard-to-reach drug users in Ukraine

People who use drugs bear a heavy HIV burden in Ukraine, where about 20% of the 310 000 PWID are infected compared with about 1% of the general adult population. Pavlo Smyrnov of the International HIV/AIDS Alliance in Ukraine described a harm reduction program run by the organization. The program has established a national network including street outreach centers providing resources such as needles, syringes, condoms, and information; mobile clinics offering HIV testing and screening; community-based centers providing testing and social and legal support; and health facilities providing substitution therapy, ART, STI and TB testing, and HBV vaccination. Since its inception, the program has reached more than 200 000 PWID, primarily men between 25 and 35 years old.

The alliance is working to connect with younger populations and female PWID, who are particularly hard to reach. The programs now ask clients to invite their injection and sex partners and their friends to come for testing and connect to care. In the past year, the centers have hired case workers to help clients, with the goal of transitioning clients within a month or two from HIV testing to treatment, a step at which many clients are lost. Between 2007 and 2013, the prevalence of HIV among PWID under age 25 dropped from 29% to 6%.

However the program faces serious challenges. Since the recent occupation of Crimea by Russia, the alliance has not been able to bring drug substitution therapy into the region and 800 clients on the therapy could lose access. The situation is likely to affect 5000 clients in the area overall. In addition, the program, primarily supported by the Global Fund since 2004, is implementing a new funding model and will lose half its budget next year. In the discussion period, Smyrnov reported the alliance is considering cost-saving strategies such as employing trained outreach workers to conduct HIV tests in place of doctors and nurses.

The International HIV/AIDS Alliance in Ukraine has reached a growing number of PWID under age 25. There has been a reduction in HIV prevalence in this population since 2007. (Image courtesy of Pavlo Smyrnov)

Extending care

Scientists, policy makers, and community representatives must find ways to reach MSM, PWID, and SW who are left in the dark without HIV care. Moderator Peter Godfrey-Faussett of UNAIDS began the panel discussion by asking Mark Harrington of the Treatment Action Group to reflect on whether MSM have become less engaged in HIV activism and with science than they were at the beginning of the epidemic. Harrington replied that activism is changing and there is still much to be done. In the past three to five years, there has been a resurgence of activism among gay men in the U.S. and possibly elsewhere. Chapters of the AIDS Coalition to Unleash Power (ACT UP) have been revived in New York and San Francisco. In New York State, the Treatment Action Group, Housing Works, and others are negotiating with Governor Cuomo's administration to adopt a plan to end AIDS and expand support programs providing housing, drug treatment, and mental health services, which will need to be built into the Affordable Care Act and Medicaid expansion. Harrington acknowledged that many gay and lesbian organizations have focused on marriage equality in the past 10 years, forming an alliance that in part arose from the AIDS movement.

Godfrey-Faussett then asked Arne Näveke of the International AIDS Vaccine Initiative whether it is reasonable to recruit participants for vaccine studies from high-incidence populations, particularly if these groups could have more limited access than others to vaccines or technologies that become available. Näveke explained that vaccine studies need statistical power to prove safety and efficacy, so research must be conducted in high-incidence populations such as MSM and SW. The same barriers that drive up HIV incidence in these populations also make people reluctant to volunteer for studies, but Näveke and others who work with these groups have opportunities to counteract discrimination and stigma. As to whether these populations could lose access to therapies, Näveke said "certainly not." He believes a vaccine would inherently counteract stigma and discrimination because it is anonymous and private.

Moving on to Ani Shakarishvili of UNAIDS, Godfrey-Faussett asked how implementation science can bring available tools to key populations. Shakarishvili explained there must be demand for implementation science and program science. She pointed to the Zimbabwean SW study as an example of program science, as a study set up to respond to a particular need for data and built on an existing network. Shakarishvili has observed that programs set up by researchers and community members can create demand for implementation science among NGOs and attract scientists. In discussing treatment for key populations, we cannot forget about prevention. As Pavlo Smyrnov's presentation showed, it is critical to link testing and prevention services to care. Strong science and activism in support of HIV treatment is also critical to convince politicians of its efficacy when countries such as Russia present evidence against substitution treatment.

Godfrey-Faussett next asked Mitchell Warren of the AIDS Vaccine Advocacy Coalition (AVAC) why it takes so long to go from drug trial to implementation and how the process could be expedited. Evidence that PrEP can prevent HIV came out three or four years ago, yet few people are using PrEP and few groups recommend it. Warren replied that how to implement PrEP has been the topic of debate for several years. Nonetheless, it is only possible to envision the end of the epidemic because of recent efforts to scale up interventions. Warren reminded the audience that science is hard, but delivery is harder. Programs, policies, and communities, not guidelines, deliver drugs. Although PrEP progress has taken longer than many wanted, the U.S. is hammering out how to deliver these products to scale. The research agenda should be based on the needs of communities and key populations and focused on implementing initiatives to demonstrate PrEP.

Godfrey-Faussett concluded the discussion by asking the panelists to comment on the most important next step to improve outcomes for vulnerable populations. Warren offered his view that the categorization of key populations can be overwhelming and can exclude people; it is also important to define high-incidence regions. Shakarishvili said the most vulnerable and poorest people could be left behind as others use prevention programs, meaning that program scale-up could widen health disparities. Näveke seconded Warren's cautionary note about categories and argued for a two-pronged approach that responds to the needs and constraints of key populations and improves systems to bring existing technologies to these groups. Harrington argued that it is unacceptable to conduct small demo projects with approved drugs that we know can prevent HIV. Considering statistics such as the 12% risk of infection for a young gay black man in Atlanta, we need large, community-based, randomized, phase IV studies in key populations to reduce incidence as quickly as possible.

Closing remarks

Despite scientific and policy advances, there is intensifying resistance in some areas to the human rights, structural, and societal changes needed to reach key populations. Beyrer predicted in his closing remarks that the next phase in eliminating HIV will be the hardest; key populations could be cut off as countries move toward country ownership. The International AIDS Conference in Melbourne, Australia, this July will be an opportunity to bring this discussion to the global level in a country with a record of defending human rights and providing health care access for key populations. Loures emphasized that the focus should be on ending the epidemic. Science has drawn attention to key populations, but we now need to understand where they are located, why they are left behind, and how to bring them tools for HIV prevention and treatment.

What are the best ways for scientists, policy makers, and community leaders to deliver medical interventions to key populations?

How could program-based science and pilot programs attract scientists and NGOs to new research opportunities?

How can HIV care programs continue to provide services in the face of political and funding pressures?

How could the development of viral resistance impact efforts to bring HIV treatment to key populations?

What are the most effective ways for scientists and activists to collaborate?

How can stakeholders engage local spiritual and community leaders to bolster efforts to reduce human rights violations?