IDU study rounds out PrEP picture

Most people assume, perhaps understandably, that HIV-infected injecting drug users (IDUs) are incapable of adhering to the daily grind of oral antiretroviral (ARV) treatment. Yet this assumption appears to be contradicted by the data. More than three dozen studies have shown IDUs are just as compliant as any other high-risk group in taking their antiviral pills every day. 

Still, the notion that HIV-uninfected IDUs might adhere to a daily regimen of ARVs to prevent HIV infection seems like a stretch. But that too appears to be the case, if the results of a recently completed Phase III trial in Thailand are any indication. 

That it was possible to conduct the trial is itself surprising, given how difficult it can be to retain and keep track of this often transient population in lengthy trials, and the legal barriers that IDUs face in accessing preventive services, due to their use of illegal drugs. Syringe exchange programs are, for example, illegal in Thailand.

The findings are also significant in light of the mixed performance of PrEP in other clinical trials. PrEP, short for pre-exposure prophylaxis, involves the administration of antiviral drugs prior to HIV exposure to prevent transmission. Some high-risk populations have benefited from PrEP; others, not so much. In all cases, adherence to preventive drug regimens has turned out to be the overriding—perhaps sole—determinant of success.  

The Bangkok study, conducted by the US Centers for Disease Control and Prevention (CDC), in collaboration with the Thailand Ministry of Public Health and the Bangkok Metropolitan Administration, is the only PrEP trial so far conducted in IDUs. 

It enrolled 2,413 men and women ages 20-60 between 2005 and 2010, who reported injecting illegal drugs in the year prior to joining the study. Methamphetamine was the most common substance participants in the trial reported using prior to enrollment. 

The volunteers were randomized to receive either a daily oral dose of 300 milligrams of the antiviral drug tenofovir (TDF), or a placebo. During the follow-up visits, researchers confirmed 50 HIV infections—17 in the TDF arm and 33 in the placebo arm—indicating about a 50% reduction in HIV incidence. 

The study found efficacy was a high as 74% in individuals with detectable TDF concentrations in their blood, according to the report published June 13 online in The Lancet. Although the trial was not powered to assess efficacy in subgroups, researchers found higher efficacy in women (79%) and in those over age 40 (89%)—two groups that demonstrated high adherence to the prophylactic regimen. 

Based on the findings, the CDC is now recommending that PrEP be considered as one of several prevention options for IDUs in the United States. Thailand is also considering whether to recommend PrEP for IDUs. 

A likely reason for the success of PrEP in this study might have something to do with where the PrEP was administered. Unlike other PrEP studies, volunteers in this trial had the option of choosing directly observed therapy (DOT)—where a health care worker watches participants take their daily dosages—or taking home a 28-day supply of pills that could be replenished at their monthly follow-up visits. About 87% of volunteers chose DOT, said Michael Martin, the principal investigator in the study and a researcher at the CDC. 

DOT has been used effectively in managing the treatment of tuberculosis in high-risk populations or countries where the disease is endemic. While DOT appears to have worked well in the context of the IDU study, it remains to be seen whether this strategy—which requires daily monitoring—can be made practical and feasible in a real-world setting.

Nor is it clear how extensively PrEP will be used in any high-risk population.  Three recent studies found PrEP effective in serodiscordant couples (Partners PrEP), men and transgendered women who have sex with men (iPrEx), and heterosexual men and women (TDF2) (see Treatment Is Prevention, IAVI Report, Jul.-Aug. 2011). But two other studies conducted in high-risk heterosexual women (VOICE and Fem-PrEP) found that none of the oral and topical PrEP regimens provided additional protection against HIV, apparently because too few women used the products consistently (see A Toddler Stole the Show, IAVI Report, Spring 2013). 

Still, Martin said the IDU study at least confirms that PrEP, when used correctly, is effective in all high-risk groups. “We know it works in MSM and we know it works in serodiscordant couples and, in general, in high-risk heterosexual transmission,” he said. “This study (in IDUs) completes the picture.” 

Martin said investigators were also encouraged by the decline in high-risk behaviors observed over the course of their study. A year after enrollment, risk behaviors decreased significantly for injecting drugs (from 62.7% to 22.7%), sharing needles (18.1% to 2.3%), and reporting multiple sexual partners (21.7% to 11%), and these risk behaviors remained below baseline throughout the entire study. Martin said rates were similar in the TDF and placebo groups. 

Nor was the adherence observed in the Bangkok PrEP study unique to this high-risk population. University of Pennsylvania scientist Julie Kraut-Becher, an investigator in the AIDS vaccine trial known as Step, said that data collected from 123 HIV-uninfected females found women adhered remarkably well to trial protocols despite reporting regular use of crack cocaine and frequent unprotected sex upon enrollment. 

In fact, she said, the study found adherence to protocols higher among women who reported using recreational drugs compared to those who didn’t, though retention in this group was less likely after 12 months when compared to women who were not using recreational drugs (Sex. Transm. Infect. 87, Suppl. 1, 2011). 

Among the 123 women in the sub-analysis, 89% adhered to study protocol—in other words, they completed the vaccination schedule. Study retention a year after enrollment was even higher—93.5%. Factors commonly assumed to interfere with trial participation were not associated with adherence to study protocol or retention. 

In the Phase IIb Step study, 3,000 volunteers received three shots of Merck’s adenovirus serotype 5 (Ad5) vaccine candidate. Merck and the US National Institute of Allergy and Infectious Diseases halted immunizations in 2007 after an early analysis of the data found the regimen ineffective in either preventing HIV acquisition or reducing the amount of virus in the blood of those participants who became infected despite receiving the candidate vaccination. 

But Kraut-Becher said their sub-analysis of women who had enrolled through their clinical site in Philadelphia did provide some encouraging insights. “When given the proper support, we found [the women] receptive to following study regimens,” said Kraut-Becher. “And we have a warm and nonjudgmental staff. I think that makes a big difference.” 

Likewise, in the Thai PrEP study, Martin said, clinics operated by the Bangkok Metropolitan Administration provided social services, primary medical care, methadone, condoms, and bleach for cleaning injection equipment all free of charge. While the Thai government prohibits clinics to distribute syringes to IDUs, you can buy needles without a prescription at pharmacies.  

“This is an interesting time for HIV prevention,” he added. “If you think back a decade ago, there was nothing but negative results. Now there are some real tools to be used. We all hope a vaccine is coming. That could really make a difference.”