The End of AIDS? The science says not now

Posted on by Laurie Garrett

The End of AIDS? The science says not now

The newfound optimism that imbues this gathering of some 25,000 people in Washington, DC, is based on a few genuinely important breakthroughs. But while these insights offer hope of saving millions of lives and limiting a tidal wave of human suffering, they do not add up to the much-vaunted “end of AIDS.”

 The first breakthrough is in the cost of treatment, which has plummeted thanks to a robust generics industry that now produces more than 95 percent of all first-line therapies for HIV. The low price and high effectiveness of anti-HIV medicines have made it possible to affordably treat 8 million people living in the poorest countries on Earth, and economically feasible to double that number – at least, in terms of pharmaceutical costs.

Years ago scientists showed that very simple drug treatment of mothers and their newborns can block mother-to-child transmission of the virus, and improvements in this strategy promise to completely eliminate in utero, delivery, and breast-milk passage of HIV. Scientifically, and in terms of cost, it is entirely possible today to eliminate all spread of HIV from infected mothers to their children.

Third, there is now ample evidence that some people who receive good and consistent treatment are able to control the HIVs in their bodies so well that no viruses can be detected in their bloodstreams. And when viral levels hit zero-detectable, these individuals rarely pass HIV onto their sexual partners. This finding has spawned the notion that “Treatment = Prevention,” implying that wider access to treatment for HIV+ populations will bring the current 2.5 million new infections per year down to 1 million, or 250,000, or, some dare say, to zero.

And pushing that number down faster might be the fourth source of optimism – PrEP, or Pre-Exposure Prophylaxis – giving the anti-HIV medicines to people that are not now infected, but have sexual partners that are. Some studies show that if such individuals take their PrEP medicines religiously, every single day, they can reduce their chances of contracting HIV infection by 60 to 70 percent --- less protection than is provided by regular use of condoms, but more than any other available prevention strategy short of absolute sexual abstinence.

This package of interventions, combined with promotion of male circumcision, which dramatically reduces men’s risk of infection, has prompted U.S. Secretary of State Hillary Clinton to declare that today’s attainable goal is an “AIDS-Free Generation,” perhaps starting with current schoolchildren not only in rich countries like the United States, but also in poor nations like Swaziland and Malawi, where more than a quarter of the young adults are infected today.

“Let me begin by defining what we mean by an AIDS-free generation,” Clinton extolled. “It is a time when, first of all, virtually no child anywhere will be born with the virus. Secondly, as children and teenagers become adults, they will be at significantly lower risk of ever becoming infected than they would be today no matter where they are living. And third, if someone does acquire HIV, they will have access to treatment that helps prevent them from developing AIDS and passing the virus on to others.

“So yes, HIV may be with us into the future until we finally achieve a cure, a vaccine, but the disease that HIV causes need not be with us.”

Creating an “AIDS Free Generation” will not be as easy as the aspiration implies.

Here in the United States, where nearly all HIV-infected individuals theoretically have access to free testing, treatment and care through a mix of Federal and State programs, the new infection rate continues to come in at about 60,000 cases/year, according to the Centers for Disease Control and Prevention, and the fastest-growing sector is African American men who have sex with other African American men – that group now has an annual new-infection incidence that is higher than any West or Central African nation, and is only eclipsed by the most HIV-burdened countries of Eastern and Southern Africa, according to a nationwide survey released here at the International AIDS Conference by Harvard’s Dr. Ken Mayer. Black gay American men make up less than 1 percent of the U.S. population, but represented more than a quarter of new infections in 2011, Mayer said.

A CDC study presented here this week shows that even among men who get HIV tests, seek treatment, and stay in their clinical programs, in a third of the participants, the ARVs fail to knock out the viruses effectively enough to guarantee that they won’t develop AIDS disease or pass infection onto sexual partners. That zero-viral-load target that is the key to the “Treatment = Prevention” mantra is only achieved right now in the United States of America for about 28 percent of men and women on anti-HIV medicines.

Even more troubling, a joint Canadian/Ugandan study of 586 discordant couples living in Uganda’s second largest city of Jinja found no “Treatment = Prevention” benefit at all. In the study one member of each couple was infected with HIV, while the partner was uninfected. For some of the infected couples the infected individual was on antiretroviral treatment, in most cases for 4 years. The other couples did not use the drugs. And the results were exactly the opposite of what was expected. The ARV-using couples, which were also more likely to use condoms, had higher likelihood of passing infection than the untreated couples: New infections occurred in nine of the ARV-using couples, versus eight in the couples that were untreated. In at least this Ugandan case, treatment clearly did not equal prevention.

In Western European countries, where all aspects of HIV testing and treatment are absolutely free and readily accessible, the numbers of new infections continue  to mount, either in a stable toll from year-to-year as seen in Sweden, or in shocking escalation as is now the case among gay men in the United Kingdom. Since the earliest days of the AIDS epidemic researchers have found surges in gonorrhea are a strong harbinger of escalating sexual spread of HIV. So it is deeply worrying that a new form of fully drug-resistant, untreatable gonorrhea emerged last year and has now turned up in several European and Asian countries.

Outside of rich countries extraordinary strides have been made in increasing access to treatment, but serious challenges remain. It is one thing to say 8 million people have started taking daily medicines to control their HIV infections, but how many remain in care two years later? Studies presented at this week’s conference show that the “successful“ programs lose track of about 10 percent of their patients, but some are losing more than 80 percent. A survey by Belgium’s Institute of Tropical Medicine that was released here shows that in Tanzanian, Ugandan, and Zambian clinics between 10 to 50 percent of HIV patients are lost to follow-up within the first year of treatment. In the face of such findings it is disingenuous to claim that little more than resources are needed to scale that current 8 million on treatment up to 15 million over the next three years. There must also be systems in place that track patients, keep them on their drugs, and explain why large numbers are lost to follow-up.

Losing track of HIV patients is obviously risky for the individuals, as they may swiftly progress to AIDS illness when they miss ARV doses. But it is also risk for society, as a whole, because interrupted treatment may promote emergence of drug-resistance forms of HIV that can be passed onto sexual or drug use partners. In such cases the newly infected individual is at greater clinical risk because he is starting treatment with a virus that can outwit some of his potential medication options. Researchers are finding increasing levels of primary infection with drug-resistant forms of HIV.

A rural South African study presented this week found that only about 60 percent of the HIV patients ever achieved the zero-viral-load target in their treatment, possibly because their initial infections were with drug resistant viruses. And after just over three years on ARVs, 86 percent of them were in trouble clinically because of drug resistance. In a third of those cases the viruses had mutated to resist not only cheap first-line therapy, but more expensive second-line drugs, as well. A 50-nation World Health Organization survey, spanning 2004-2009 records, found a major contributor to rising drug resistance in poor and middle-income countries is ARV supply chain problems, both as stock-outs of the drugs and in the form of patients failing to pick up their medicines before running out of previous supplies. At 354 clinics in 21 countries, only 17 percent of patients consistently obtained their medicines on time. Worse, 35 percent of drug deliveries to clinics in these countries were late, or interrupted for extended periods of time, compelling treatment interruptions. This year in South Africa, a massive stock-out of the key HIV drug tenofovir imperiled some 600,000 patients and forced individuals to make weekly visits, rather than monthly, at clinics in search of fresh supplies.

A detailed analysis of the WHO data published before this week’s International AIDS Conference found East Africa has a startling pace of rising drug resistance, soaring at 29 percent growth per year, with an estimated 2011 prevalence of 7.4 percent. In Southern Africa the rate of drug resistance is swelling at 15 percent annually.  In this region the roll-out of ARV treatment has been robust, but results have sometimes been disappointing for the epidemic, especially in Uganda. When President George W. Bush launched his PEPFAR program in 2003 Uganda was the shining star of success, hailed as proof that the so-called ABCs – Abstinence, Be Faithful, and when not, use Condoms – was the best strategy for stopping HIV. But last month the Ugandan government acknowledged that its epidemic has reversed; in 2004 some 6.4 percent of the population – 1.2 million people -- was infected, but that has risen to 7.3 percent, or 2.4 million.

PrEP currently costs $13,500/year, which will limit utility of that prevention approach outside of wealthy countries. It is predicted that Gilead, the U.S. company that manufactures the drug approved by the FDA for PrEP, will now be targeted with demands to lower its price or allow generic manufacture of PrEP formulations of the patented drug. As access to PrEP becomes a wider reality, many worry that HIV-free individuals will not take the medicine every single day, and that supplies will find their ways into the black markets, sold as treatments or “day after” sex pills to unsuspecting customers. This could fuel more drug resistance.

Several studies in various populations around the world – especially within couples where one partner is HIV+ and the other is free of the virus – seem to prove the cynics wrong, showing that discordant couples use PrEP properly, thereby dramatically reducing the chance that the infected individual passes HIV to the PrEP-taking partner. A discordant couples study run by the University of Washington found PrEP very effective in Uganda. According to their presentation this week, couples given the pills were 72 percent less likely to transmit HIV from the HIV+ individual to the uninfected compared to non-PrEP couples. In his speech to the Conference, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases summarized what was known about the effectiveness of PrEP in multiple settings where the reduction of HIV transmission ranged from zero to nearly 50 percent. Fauci said that in the best studies, the effectiveness approached 60 percent.

But this is not always the case – especially when PrEP is used outside of the confines of clear sexual relationships. One study presented this week was especially sobering. In Thailand, a joint Thai/American study tried using PrEP to lower HIV acquisition rates among IV drug users in Bangkok. People who inject drugs often share their needles and narcotic preparation equipment, passing HIV among groups of users. The researchers gave 2,413 drug users PrEP at methadone clinics, along with diary cards in which they wrote down every time they ingested the anti-HIV pills. After 84 days the mean level of tolerable adherence, defined as taking the pills at least 5 days a week, was only 52 percent, and a quarter of the participants hardly took the pills at all. Only 29 percent of the PrEP study participants took their pills properly, every day. This was especially troubling because the Bangkok study involved careful counseling, and all of the participants were individuals motivated to get off of heroin and other drugs they were using – which is why they were in methadone clinics. In a more real world setting, allowing millions of drug users around the world routine access to PrEP, adherence to proper pill-taking would be problematic.

In the 1990s American scientists showed that they could prevent pregnant HIV+ women from passing their viruses onto their fetuses or newborns through very simple, extremely inexpensive use of anti-HIV pills. The easy strategy was so effective in the U.S. that the likelihood of a mom passing her HIV to her child in America dropped from about 30 percent in 1994 to less than 1 percent today. The United Nations declared that among its 2015 Millennium Development Goals is complete worldwide elimination of mom-to-baby HIV spread, and the target seemed reasonable because the entire toolkit necessary to make it so is cheap, well understood, and easy to execute. Global roll-out of this scheme was agonizingly slow until 2009, when UNAIDS pushed it to the top of the HIV agenda. Between 2009-2011 there was a 25 percent reduction in the numbers of babies born with HIV. But that still means 270,000 babies acquired HIV last year. Clearly “easy” isn’t always globally easy.

Finally, Dr. Chris Beyrer of Johns Hopkins Medical School wisely warns that even a thriving, robust HIV treatment and control effort will only put us at, “the beginning of the end of epidemic HIV,” but do little to stop flourishing sub-epidemics among the most disadvantaged and politically isolated populations. At the top of that list are intravenous drug users, particularly in countries that have denied these young people access to sterile syringes and narcotic substitution drugs like methadone and humane healthcare. The fastest growing epidemics in the world today are found in former-Soviet nations, such as the Russian Federation, Ukraine, and Kazakhstan, where HIV+ drug users are far more likely to find themselves imprisoned than treated with anti-HIV medicines. Methadone and other substitution drugs are illegal in nearly all of the former USSR. Not coincidentally, these countries are witnessing explosions of multi-drug resistant tuberculosis, spreading like wildfire through their untreated HIV populations.

If promises are to be made, they must realistically and honestly be for all people infected with the virus, or at high risk of infection. If promises are made they must not be limited to starting individuals on anti-HIV medicines, but to keeping them on the drugs for decades, and to treating the longer term ailments and side effects that we see cropping up with frightening frequency in the HIV+ populations of Europe and North America. If promises are made, they must be funded – not only by American taxpayers, but by the whole world in a shared burden. And if promises are made their achievement must be measured, accountable, and real.

NEXT: The end of AIDS? Who will pay for it?