AIDS 2016: Significant Progress but Still an Uphill Battle

Faltering prevention efforts and funding questions combine with excitement about cure and vaccine research to paint a complex picture of the AIDS epidemic in its fourth decade.

By Michael Keller

In 2000, when the international AIDS community gathered in Durban, South Africa, no less than Nelson Mandela gave the marching orders. “In the face of the grave threat posed by HIV/AIDS, we have to rise above our differences and combine our efforts to save our people,” he implored the audience. “History will jAIDS2016udge us harshly if we fail to do so now, and right now. Let us not equivocate: a tragedy of unprecedented proportions is unfolding in Africa.”

Nearly two decades later, some 15,000 researchers, advocates, and policymakers flooded into the city’s International Conference Center for AIDS 2016. This meeting, the 21st International AIDS Conference, started, appropriately enough, on the Rainbow Nation’s Nelson Mandela Day. If the great man were present in the halls and exhibition spaces to take in the events that swirled about Durban on July 18-22, he would likely have had mixed feelings. Researchers presented sobering findings about the increase in new infections in several countries, the failure to reach marginalized people at the highest risk of contracting HIV, and the virus’s emerging drug resistance. At the same time, vaccine trials are moving forward and work continues toward developing a cure that eliminates the virus or provides long-term remission. During a time when AIDS must compete with terrorism, other emerging diseases, and turbulent politics for the world’s attention, the week of the AIDS 2016 conference brought the complexities and realities of the global epidemic into relief.

From despair to progress

In the intervening 16 years since Durban last played host, huge strides have been made in treating those infected with HIV. At the time of the 2000 conference, a watershed moment that got the international community working in concert to face the epidemic, a meager 690,000 HIV-infected people were receiving antiretroviral therapy (ART). By 2015, those receiving the lifesaving drugs had jumped to 17 million in a herculean feat of scaling that many thought was impossible. Because of that, the number of people dying from AIDS fell from 2.8 million in 1999 to 1.1 million in 2015. Mother-to-child transmission rates are also falling around the world, with many countries close to stopping it, and others like Thailand and Armenia eliminating it entirely. In South Africa alone, efforts over the last five years have reduced mother-to-child transmission by 84 percent. Because of these and other prevention efforts, 2.1 million people acquired HIV in 2015 compared to 5.4 million in 1999.

“Sixteen years ago, Nelson Mandela addressed the International AIDS Conference here in Durban. He called it, ‘A gathering of human beings concerned about turning around one of the greatest threats humankind has faced,’” said UN Secretary-General Ban Ki-moon. “He called for access to treatment equity and human rights. That was a turning point that led to remarkable global progress. For every one person who received lifesaving treatment back then, there are now 17 who have it today.”

The massive scale-up in access to ART is encouraging, but much more remains to be done. There are still nearly 20 million people around the world in need who aren’t receiving ART. And just getting more and more people on treatment may not be enough to end the epidemic.

Many researchers had hoped that increased access to treatment as early as possible after a person discovers they are HIV infected would be an effective means of prevention. The idea behind this strategy is that the drugs would decrease virus levels enough that HIV would not be transmitted as readily, and therefore new infection rates would decline. A previous study had shown that providing ART to the HIV-infected partner in a discordant couple could reduce virus transmission by 96 percent (Curr. Opin. HIV AIDS 7, 99, 2012). But this treatment as prevention (TasP) approach suffered a major blow in Durban.

Investigators released findings during the conference from the first phase of a large study called ANRS 12249, which was evaluating TasP in South Africa. In this study, researchers used the “test and treat” strategy of universally testing people for HIV and immediately offering ART to those infected (PLOS Med. 2016, doi: 10.1371/journal.pmed.1002107). The work involved almost 13,000 volunteers in a rural part of KwaZulu-Natal province. Randomized communities of participants were broken into two arms—one where all HIV-infected participants were offered immediate access to ART, and a second where only those whose CD4+ T-cell counts fell below 350 (the South African standard for ART initiation) received treatment. All participants were given at-home HIV testing and those who were infected were sent according to their study arm to a TasP clinic within a 45-minute walk from their home.

An initial survey by investigators offered hope that infected people would quickly start on treatment. Ninety-three percent of participants said that they would want to start ART as soon as possible if they learned they had HIV. Those who actually sought treatment once they learned their status, though, fell far from expectations. In fact, easy access to testing and ART did not incentivize the majority to begin treatment. Only 47.5 percent of infected participants sought care within the first six months of learning they had HIV and new infection rates did not go down among this group. The authors said reluctance to start treatment by those who found out they were HIV infected could be the result of at-home testing, which may have identified infection before symptoms occurred. They are also investigating whether stigma could play a role in reluctance to get treatment, since community members know that only those who are HIV-infected go to the clinics.

Prevention efforts failing

So while the number of people accessing ART has increased dramatically, the end goal—made concrete by the Joint United Nations Programme on HIV/AIDS (UNAIDS) objective of ending the epidemic by 2030—hinges on keeping people from getting infected in the first place. And if Mandela were in attendance at AIDS 2016, he would have noted delegate after delegate proclaiming how much work remains to be done to do just that.

“Let me say clearly that I am scared,” said Michel Sidibé, the executive director of UNAIDS. “We are back in Durban in difficult times. The world is facing many competing priorities. Terrorism. Migration. So many issues.”

He continued: “I am seeing for the first time the decline in financing from donor countries—13 out of 14 reduced their contribution to the response... If we continue with this trend, we will not be able to end AIDS by 2030. The risk is that we will have a rebound in this epidemic. We will have resistance. We will lose our investment and we will have to pay more later.”

Indeed, a number of researchers and analysts revealed evidence at conference sessions that substantiated Sidibé’s fears. Perhaps the most troubling came from a new epidemiological study published on July 19 in The Lancet HIV that took a second look at how the rate of new HIV infections is calculated. Whereas statistics on the number of people living with HIV and annual deaths caused by the virus are benchmarks for the success of treatment efforts, the rate of new infections is a major indicator used to measure progress in prevention.

In 2005, 4.9 million people became infected with HIV, a number that began decreasing rapidly because of education and behavioral changes. But in the most recent UNAIDS update that came out before June’s UN High-Level Meeting on Ending AIDS, the organization reported that “declines in new HIV infections among adults have slowed alarmingly in recent years,” with the total number of new infections remaining basically unchanged at around 2.1 million since 2010. Now, according to the new study, the picture is significantly bleaker. More than 1,700 collaborators from 124 countries poured over data from the comprehensive 2015 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Researchers improved the estimation process, they said, by updating and including prevalence rates from national surveys and antenatal care clinics, demographic input on fertility and migration, mortality on and off ART, and background HIV-free mortality. They also improved how UNAIDS’s epidemiological programs are integrated into the analysis to improve estimates of HIV incidence for countries not included in UNAIDS’s process. Their work, which they say are “the most comprehensive and internally consistent assessments of the levels and trends of HIV/AIDS incidence, prevalence, and mortality worldwide so far,” concluded that 74 countries actually had an increased rate of new infections over the last decade. Countries as diverse as Egypt, Mexico, Russia, and the Philippines all had an uptick in infections (Lancet HIV 3, e361, 2016).

Haidong Wang, a University of Washington demographer and lead author of the study, said the findings point to the size of the challenge to meet the UN goal of eradicating AIDS by 2030. “The obvious conclusion is that much still needs to be done,” he said. In fact, he and his colleagues say their findings cast significant doubt on whether the world can even achieve UNAIDS’s 2020 interim goals, collectively known as the 90-90-90 targets: getting 90 percent of all people living with HIV to know their status, 90 percent of all people with diagnosed HIV infection on ART, and 90 percent of all people receiving ART to have their virus successfully suppressed.

In a commentary published alongside Wang’s study, Sorbonne University’s Virginie Supervie and Dominique Costagliola say this new way of tracking incidence is far more than an update that opens a new avenue for understanding the epidemic (Lancet HIV 3, e337, 2016). According to Supervie and Costagliola, the refined model also points to significant blind spots and incongruities with the official UNAIDS data that must be corrected. “The GBD estimates of HIV incidence are significantly lower (two to ten times) than the reported number of newly diagnosed HIV cases for most countries in North America, Europe, Central Asia, and Australia,” they write. “The study reveals that there are still large uncertainties and gaps in knowledge about the HIV incidence in many settings. Without timely and reliable assessment of HIV incidence it will be impossible to end the HIV epidemic.”

Resistance peaks its head  

The unprecedented public health effort to identify HIV-infected individuals and get them on antiretroviral treatment has kept millions alive. But the spread of drug resistant virus, which occurs when the virus develops mutations that make it less susceptible to certain antiretrovirals, is on the rise globally.

A World Health Organization (WHO) technical report released in July found that HIV drug resistance is now being found in more than a fifth of people just starting antiretroviral therapy (ART) in some low- and middle-income countries. In Cuba, drug resistance was observed in 22 percent of treatment-naive patients. And perhaps more alarmingly, drug resistance was found in up to 37 percent of patients who have stopped and then restarted treatment in some countries.

WHO modeling has determined that if drug resistance rises to more than 10 percent of treatment-naive patients in sub-Saharan Africa alone, an additional 420,000 deaths and 300,000 new infections could follow in the ensuing five years. Since those with drug-resistant HIV would continue spreading the virus to others while on first-line treatment and would need to be put on more expensive second- and third-line therapies, the WHO estimates that ART program costs could balloon by nearly US$3 billion.

“These are early warning signals popping up in countries around the world,” said Silvia Bertagnolio, medical officer with the WHO’s HIV Drug Resistance Team. “We can say that, as of 2013-2014, we’ve started seeing alarming levels of drug resistance.” She says the WHO is now recommending countries perform resistance surveys. “The only real answer to stop the spread of HIV drug resistance is a vaccine,” said Bertagnolio. —M.K.


Highest risk communities forgotten

As community advocates took the stage on ensuing days, it became clear that one of the largest hurdles to preventing new infections—absent an effective cure or vaccine—is reaching the most vulnerable communities. Speakers repeatedly called for meaningful access to prevention and treatment programs for men who have sex with men (MSM), young women, the transgender community, sex workers, injection drug users, and prisoners. Reaching these people is key to getting the epidemic under control since 90 percent of new infections in Central Asia, Europe, North America, the Middle East, and North Africa in 2014 occurred in these groups.

Ben Plumley, CEO of Pangaea Global AIDS, said he and many others had been greatly disappointed with the outcome of June’s UN High-Level Meeting. During a pre-conference session, he and others voiced concern that the tone of officials is that the page has been turned on AIDS. “All the governments at the [UN High-Level] meeting said the fight against HIV is over—all that is left is the AIDS benefit concert,” Plumley said. “Yes, we have had some progress in treatment since 2001, but we’ve failed fundamentally in prevention. Yet again, our governments couldn’t bring themselves to speak of the communities that will turn this epidemic around.”

Perhaps the most invisible of the key populations that need access to prevention and treatment are the world’s 10.2 million men, women and children being detained as prisoners. According to a special edition of The Lancet released in time for AIDS 2016, this population is at especially high risk of HIV. Modeling showed that 3.8 percent of the population have HIV, compared with a global prevalence rate of 0.8 percent in 2015 (Lancet 2016, doi:10.1016/S0140-6736(16)30466-4). One reason for this is the drug laws that criminalize intravenous substance abuse, forcing many already HIV-infected individuals to concentrate in prisons.

Also at particularly high risk are girls and young women aged 15 to 24. UNAIDS’s official statistics show that in sub-Saharan Africa, this group now accounts for 25 percent of new HIV infections among adults, and women of all ages make up 56 percent of new infections among adults. The organization says this unequal burden is the result of harmful gender norms, insufficient access to education and sexual and reproductive health services, poverty, food insecurity, and violence. “Fifty-six percent of people with HIV are women. Funders must put their money where the problem is,” said activist Yvette Raphael. “Women are at the center of this and I can say we are nowhere near the end of HIV/AIDS. We are still dealing with some of the same issues we were dealing with 15 years ago when I was diagnosed.”

The plight of girls and women resurfaced throughout AIDS 2016, with experts from different specialties saying that as women go, so too goes the effort to eradicate the disease. “We must think gender,” said Elizabeth Bukusi, co-director of the Kenya Medical Research Institute-University of California, San Francisco Training Program. “Gender matters for prevention. Gender matters for treatment. The goals we’ve set for 2020 are off-track. A reason for that is our inattention to gender.”

Realizing the need, many projects are taking a more aggressive approach to controlling HIV in these at-risk populations. Some start organically, like a Kenyan advocacy group securing ART for its community that began as a group where ostracized women with AIDS took care of others as they died. Vancouver, meanwhile, is now one of dozens of cities around the world offering injection drug users supervised injection sites, safe fix rooms that give them access to clean needles and healthcare services. San Francisco and other US cities are now considering launching their own. Meanwhile, Thailand has launched an online program that offers supervised HIV self-testing, counseling, and registration at treatment clinics. The program hopes to reach more MSM and transgender women where they already network in the digital space.

Improving prevention

Leaders in the research and advocacy communities agreed that at-risk people, especially those comprising the now globally recognized key populations, need access to every prevention tool currently available: clean needles for injection drug users, condoms, pre-exposure prophylaxis (PrEP), and voluntary adult male circumcision. But having the tools, getting them into the hands of those who need them most, and then seeing they are used effectively and consistently are three very different things.

Nduku Kilonzo, the director of Kenya’s National AIDS Control Council, lamented how her country has not yet effectively gotten the message out about using protection during sex. “We invest a lot in the new kid on the block and remove money from older things we know work well like condoms,” she said. “In Kenya, every single young person knows where to go to get more airtime for their mobile phones. What have we done wrong that they don’t know where to get a condom?”

New evidence also reinforced that social changes can themselves act as protective measures. One recent study looked at whether increasing schooling in Botswana had any effect on new infection rates (Lancet Glob. Health 3, e470, 2015). Researchers found that each additional year of schooling reduced the risk of infection by 8.1 percent in study participants. Women benefitted more than men, seeing a risk in reduction from the country’s baseline prevalence by almost 12 percent.

Researchers also discussed a new way to use PrEP, which they say increases the options for those who might not want to take a pill every day. Early studies showed that administering the antiretroviral Truvada (a combination of tenofovir disoproxil fumarate and emtricitabine) one, three, or seven days before and two hours after rectal exposure to a simian immunodeficiency virus (SIV)/HIV hybrid (SHIV) protected rhesus macaques as well as a daily dose (Sci. Transl. Med. 2(14), 14ra4, 2010). Another study found that pigtail macaques given a Truvada dose a day before and two hours after vaginal virus exposure were all protected from infection, whereas all controls were infected (PLoS ONE 7(12), e50632, 2012).

Then last year, the ISHEGAY study involving 400 MSM showed that when participants took Truvada before and after sex, there was an 86 percent relative reduction in the incidence of HIV acquisition (N. Engl. J. Med. 373, 2237, 2015). Specifically, volunteers were told to take two pills two to 24 hours before sex, another pill a day after taking the first two, and a fourth pill a day after that. Jean-Michel Molina at the University of Paris Diderot, who led the ISHEGAY research team, said the availability of on-demand PrEP isn’t for everyone since it requires premeditation and planning in advance of sexual encounters. Robert Grant, an investigator at the University of California, San Francisco School of Medicine, said that while sexual event-driven dosing is complicated, it might find a receptive audience among those who have “seasons of risk,” where higher-risk behavior happens infrequently. “There are some who do very well with on-demand, particularly older gay men,” Grant said. “If you’re having risky sex once a month or less, there’s really no call to take a pill every day.”

Hope in the vaccine research community

Even if all existing HIV prevention options are implemented well, at least a dozen speakers at AIDS 2016 said an effective vaccine would be humanity’s best chance to end AIDS. “The only way we’ll eliminate HIV in the next 100 years is with a vaccine. There’s no other way,” said Paul Stoffels, the executive vice president and chief scientific officer of Johnson & Johnson.

The energy propelling the scientific search for a vaccine has ebbed and flowed over more than three decades of cyclic excitement followed by dashed hopes. One period of heightened enthusiasm was driven by the unexpected efficacy seen in 2003’s now well-known RV144 trial of a prime-boost genetically engineered viral vector and protein, which lowered the rate of infection by a modest 31 percent in participants over the three-and-a-half year study. These results offered the first evidence of vaccine-induced protection against HIV.

Now, interim results announced in Durban from HVTN 100, a small ongoing study of 252 people in South Africa that was designed to test a modified RV144 vaccine regimen in a high-risk population, has green lighted the next step. Later this year, researchers will start enrolling participants in South Africa in the HVTN 702 study, a Phase III randomized controlled trial of 5,400 adults aimed at preparing the experimental vaccine for licensing in South Africa (see In Brief, this issue). “All the criteria were met unequivocally and, in many instances, the HVTN 100 outcomes exceeded both our own criteria and the immune responses seen in RV144,” said Linda-Gail Bekker, chair of the HVTN 100 protocol and deputy director of the Desmond Tutu HIV Center. Results of HVTN 702 are expected in 2020.

Another area of vaccine research generating buzz is the recently started large-scale trial involving passive administration of broadly neutralizing antibodies to uninfected individuals in the hope of preventing HIV infection. Antibody-mediated prevention (AMP) turns the idea of vaccination on its head—instead of the normal method of presenting the body with an immunogen so that it starts making antibodies, it arms participants with the antibody itself. The research community has shown that introducing antibodies into nonhuman primates can confer protection against the monkey equivalent of HIV, but there has not yet been enough human data to support the idea that it also works in people. One such broadly neutralizing antibody, VRC01, prevented infection in animal models, and was found to be safe and well tolerated during three Phase I trials with 140 human participants. This antibody is now being tested in Phase IIb clinical trials. During the project, called the AMP Study, 2,700 MSM and transgender participants in the Americas (HVTN 704/HPTN 085) and 1,500 heterosexual women in sub-Saharan Africa (HVTN 703/HPTN 081) will receive the VRC01 antibody. As of the conference’s start, 19 of 24 sites in the Americas had been activated and 249 participants were enrolled. In Africa, five of 15 sites had been activated and 29 women were enrolled. During the double-blinded, randomized study, patients will receive either a low- or high-dose of the antibody or a placebo. In the studies, participants will receive a total of 10 antibody infusions, one every eight weeks, with a follow-up 20 weeks after the last infusion. Final results are not expected until 2022.

Another approach undergoing clinical testing involves a different viral vector/protein prime-boost combination than that being studied in HVTN 702. One study published last year showed that using an adenovirus serotype 26 (Ad26) vector prime loaded with clade B HIV Gag, Pol, and Env viral protein sequences followed by a purified HIV clade B HIV Env gp140 boost, protected half of inoculated rhesus monkeys against multiple rectal SIV challenges (Science 349 (6245), 320, 2015). An ongoing Phase I/IIa trial called APPROACH is assessing this regimen’s safety, tolerability, and immunogenicity with the addition of a modified vaccinia Ankara (MVA) poxvirus vector carrying HIV Env, Gag, and Pol proteins (see The Confidence Booster, IAVI Report, Vol. 20, No. 2, 2016).

At the conference, Hanneke Schuitemaker, the head of viral vaccine discovery and translational medicine at Janssen Pharmaceuticals, said all 400 participants in the APPROACH study were recently given their third vaccination at the trial’s six-month mark. A fourth booster injection that includes combinations of Ad26, MVA, and gp140 will be given at the 48-week mark, with a 12-month follow-up. She said another Phase I/IIa study, called TRAVERSE, enrolled its first volunteer in July. This trial will test a candidate that does not include MVA, and adds a clade C Env insert into the Ad26 prime and boost. A third trial, called ASCENT, is expected to begin in the fourth quarter of 2016 and will test a clade B mosaic gp140 insert in the boost. Mosaic HIV immunogens are computationally derived proteins designed to maximize coverage of the many circulating strains of HIV. The collaboration running these trials hopes to find, among all the different combinations, a regimen that elicits a balanced immune response against HIV variants in clades A, B, and C.

Yet one more strategy is using replicating vectors to induce sustained immune response against HIV. Nicole Frahm of the Fred Hutchinson Cancer Research Center said a few different designs centered on replicating vesicular stomatitis virus (VSV) vectors, including one created at IAVI, are in, or will soon be moving into, clinical trials after showing efficacy in animal studies.

Even with all of this, many speakers modulated their enthusiasm about the current state of vaccine research in acknowledgement of the long road still ahead and the formidable challenge presented by the rapidly mutating and diverse virus. “If our efforts in developing an HIV vaccine are successful, this feat will represent the most creative, elegant, and complex approach toward vaccine development in scientific history,” said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

And getting there will require serious funding, a state of affairs that is not a given.

A long road to a cure  

News from AIDS 2016 on the search for a cure didn’t leave much hope for a breakthrough anytime soon, though there was no shortage of discussion, with two full days devoted to the topic the weekend before the official conference began.

Perhaps the largest obstacle researchers face in curing HIV is a phenomenon called viral latency, where HIV hides in certain tissues and other reservoirs in the host’s body to evade immune system attack. During a presentation on measuring the HIV reservoir, Asier Sáez-Cirión, a virologist at the Institut Pasteur in France, said the state of the art assays only identify infected cells where the virus is actively replicating. Researchers must still identify a marker for cells infected with latent virus that remain suppressed during treatment, but quickly starts replicating after treatment stops. Differentiating between cells with latent infection and those that are uninfected is challenging, but new work shown by Sáez-Cirión using single molecule assays that are much better at quantifying p24, a protein that comprises most of the viral capsid, has offered a nearly 3-log boost in sensitivity (Passaes et al., submitted). Finding cells where the latent virus is hiding is key to identifying and eventually destroying HIV reservoirs.

In pediatric cases, antiretroviral therapy (ART) itself might hold the key to long-term remission from HIV infection. Deborah Persaud at Johns Hopkins Medicine has been studying the case of a Mississippi baby who was administered a three-drug ART regimen starting 30 hours after birth (NEJM 369, 1828, 2013), after HIV DNA and RNA were detected in blood samples. The child remained on ART for 18 months, during which time doctors found that HIV RNA, proviral DNA, and HIV-specific antibodies all reached undetectable levels. Over the course of more than two years with no treatment, the virus remained in remission until it unexpectedly returned. “We failed to detect any HIV in the child. No trace of infection,” Persaud said. “And yet, HIV resurfaced 27 months later. We could identify no events that triggered the rebound.”

Studies have pointed to an infant’s gastrointestinal tract, specifically CD4+ CCR5+ T cells in the gut mucosa, as a productive place for HIV to replicate and start establishing reservoirs after mother-to-child transmission. Subsequent review made Persaud and her team believe that very early ART delayed viral rebound by significantly reducing these reservoirs in the Mississippi baby’s body (Curr. Opin. HIV AIDS 10(1), 4, 2015). She and her colleagues now believe the road to a pediatric cure starts with combining early diagnosis and very early ART treatment. In her talk, Persaud said she is also excited about therapies harnessing the power of broadly neutralizing antibodies that can act against a wide variety of HIV strains.

Sáez-Cirión and his team are also investigating a class of very rare infected adults whose systems can spontaneously control viremia (J. Virol. 90(13), 6148, 2016). They believe these so-called HIV controllers could hold the secret to initiating long-term remission by their innate ability to limit the formation or maintenance of HIV reservoirs in their bodies.

Increased funding for cure research is helping fuel much of this work. The International AIDS Society and the HIV prevention advocacy organization AVAC reported funding for cure-related research has more than doubled since 2012 to over US$200 million in 2015. “An HIV cure is not happening tomorrow morning, but is it a Mission: Impossible? I think not,” said Olivier Lambotte, a doctor who works at the intersection of cancer and HIV. —M.K.


Funding the tools

Advocates and authorities sounded an alarm that decades of advances against the disease could be reversed without countering mounting indifference among donors, governments, and the public. A major report released by the Kaiser Family Foundation and UNAIDS just ahead of Durban found that donor government funding for HIV programs in low- and middle-income countries fell by more than a billion dollars in 2015, the first decline in five years. The analysis found that funding from 13 of 14 donor governments fell or remained the same last year. The US continued to provide the vast majority of funding for the global AIDS fight, contributing $5 billion last year, or 66.4 percent of the global total.

Meanwhile, the investment in global HIV prevention research has also been declining from a 2012 high of $1.31 billion to $1.18 billion in 2015. “We’ve heard a lot of talk about the end of HIV during this conference,” said Thomas Fagan, a health financing and policy analyst at Palladium. “I think we need to temper that a little and find the donors and find the funding to move us forward.”

During a time of tightening purse strings, many low- and middle-income countries will need to find more money domestically to maintain funding levels for AIDS programs. But a major obstacle to increasing a country’s domestic contribution to health programs or any other services, especially in Africa, is the rampant corruption that sees billions of dollars diverted every year. “We have the money. Our people are suffering not because we are poor, but because we are mismanaging our resources,” said Ruth Labode, a member of Zimbabwe’s parliament. “We have corruption. Zimbabwe is not poor. Kenya is not poor. But the national budget in Zimbabwe is $5 billion and $15 billion walked out of the country.”

The international and domestic funding situation is just one obstacle to contend with. The messages coming out of Durban were clear: to achieve the UN target of eradicating AIDS by 2030, access to treatment must expand, prevention efforts must improve, key populations must be reached, and new infection rates must come down. “We are not going to end AIDS with the tools we have,” said David Wilson, the World Bank’s global AIDS program director. “What an extraordinary success we’ve already had in treating the infected. But it’s also increasingly clear that in the real world tablets are not going to stop this epidemic. We have to reinvigorate R&D. We’ve never stopped a disease without a vaccine or a cure.”

Michael Keller reports from the frontiers of science, technology, and international affairs. His writing has appeared online and in newspapers, magazines, and books, including the graphic novel Charles Darwin’s On the Origin of Species.