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AIDSmeds in Mexico: Notes From the XVII International AIDS Conference
by Tim Horn
The largest gathering of AIDS experts concluded August 8 with a number of new findings that will undoubtedly impact HIV prevention and treatment, both here and abroad, for years to come. We present highlights from our coverage of the XVII International AIDS Conference in Mexico City.
It bills itself as the largest and most diverse gathering of researchers, health care providers, policy experts, government leaders, activists and people living with HIV/AIDS. And you won’t likely get an argument from the 25,000 delegates who attended the XVII International AIDS Conference (IAC) to see, hear and discuss more than 7,800 abstracts selected for presentation. Held in the massive lecture halls of the Centro Banamex Convention Center in Mexico City, the event lasted August 3 to 8.
This year’s conference theme, “Universal Action Now,” emphasized continued urgency in the worldwide response to the HIV pandemic. Those of us from AIDSmeds and POZ fortunate enough to attend the conference met with and learned from the international roster of experts—ranging the rural health care providers in Malawi and Brazil to researchers in Mexico and Botswana and activists in Peru and Thailand. We attained a deep respect for the intricate meshwork of science and policy that’s required to achieve universal access to best-possible HIV prevention, treatment and care.
This web exclusive reviews highlights from this year’s conference. An even more complete list of our IAC reports—articles and video interviews are still being added—can be accessed via our official coverage page.
Starting and Switching Treatment
Clinical trials and other studies—along with improvements in the medications used to battle HIV—continue to shape answers to the big treatment questions, including when to start, what to start with, when to switch and what to switch to. New data presented at IAC underscore the fact that the art of HIV treatment truly is a work in progress:
Sustiva—compared with Kaletra (lopinavir/ritonavir)—may be the best option for those starting therapy with very low CD4s, according to a study conducted in Mexico, where many people living with HIV don’t find out they’re infected until late in the disease process. CD4s at the start of the 189-patient study averaged 60 cells. After 48 weeks of treatment with Sustiva and Combivir (zidovudine/lamivudine), 70 percent had undetectable viral loads, compared with 53 percent of those receiving Kaletra plus Combivir. While the study’s single-country focus prevents far-reaching conclusions, the authors say that the data are strong enough to help guide treatment decisions for patients with advanced HIV infection.
Some confusion surrounds the effectiveness of Epzicom as a regimen component for those with high viral loads (VLs) and just starting treatment. In the 1,600-patient ACTG 5202 study, volunteers with VLs above 100,000 copies who began treatment with regimens containing Epzicom had a more difficult time keeping their VLs undetectable and were more likely to experience moderate-to-severe side effects, compared with those taking regimens that included Truvada. However, an analysis of six clinical trials reported at the conference by GlaxoSmithKline, Epzicom’s manufacturer, indicates similar safety and efficacy among patients with viral loads both above and below 100,000 copies. GSK says it’s working closely with the ACTG to understand why these two analyses found conflicting results.
Isentress (raltegravir) may be approved only for treatment-experienced patients, but new long-term data suggests that it works just as well as Sustiva—potentially with fewer side effects—in those starting therapy for the first time. The FDA will soon review Merck’s twice-daily integrase inhibitor for treatment newbies.
Phenomenal responses to treatment were reported in a small French study evaluating combos containing Isentress, Intelence (etravirine) and Norvir-boosted Prezista (darunavir) in heavily treatment experienced patients. Roughly 90 percent of the 103 study volunteers, averaging 13 years of prior antiretroviral (ARV) use, had viral loads below 50 copies after 24 weeks—a better success rate than found in many studies involving first-time treatment takers!
For ARV treatment to work, people need to feel comfortable using it—and a survey reported at the conference suggests that many fear side effects to the point that they avoid or stop therapy. An International Association of Physicians in AIDS Care survey of nearly 3,000 people living with HIV in 18 countries found that 26 percent elected not to seek treatment because of perceived toxicities. Thirty-four percent of treatment-experienced respondents discontinued their meds because of side effects.
Promises in the Pipeline
Pharmaceutical and biotechnology researchers are currently testing more than 90 drugs for HIV/AIDS, according to the Pharmaceutical Research and Manufacturers of America (PhRMA). Video interviews with Andrew Carr, MD, of the University of New South Wales in Sydney, and Sharon Walmsley, MD, of the University of Toronto, along with the following news stories, report on the latest in experimental ARVs discussed at IAC.
Tibotec’s experimental non-nuke rilpivirine (TMC-278) appears to work just as well as Sustiva in a 96-week study, with fewer side effects. While researchers want to learn more about abnormal heart rhythm measurements seen in some patients taking different doses of the drug, that issue was less of a concern in those taking once-daily 25 mg rilpivirine—the dose being studied in Phase III clinical trials.
Ardea Bioscience’s RDEA806 and Idenix Pharmaceutical’s IDX899, two non-nukes with activity against HIV resistant to approved members of this drug class, both showed promise in two seven-day studies. Next up: Phase II clinical trials in both treatment-naïve and treatment-experienced patients.
A tablet version of Norvir (ritonavir), often used to boost blood levels of other PIs, is on the way. While it’s not clear whether it will have fewer side effects than the current capsule formulation, its heat-stable structure means no refrigeration required—good news in low- and middle-income countries. Look for it in 2009.
Complications of HIV and Its Treatment
AIDS-related problems may not be as frequent thanks to the availability and proper use of HIV treatment, but life with HIV is not without other health concerns—including ARV side effects. But researchers continue to make headway in figuring out what causes them, who is at greatest risk and what can be done about them.
A second study is suggesting a possible link between the nucleoside analogue abacavir—found in Ziagen, Epzicom and Trizivir—and heart attacks in people living with HIV, notably those with several other risk factors for cardiovascular disease (e.g., smoking, high blood pressure, diabetes). The quadrupled risk found in the SMART study echoes findings from the 33,000-patient D:A:D study reported earlier this year. In a separate presentation at IAC, however, an analysis of 54 clinical trials in which abacavir was used failed to find any such increased risk. Both sides agree that much more comprehensive heart data from a large and long-term clinical trial will ultimately be necessary to determine whether abacavir truly is linked with, and a cause of, increased cardiovascular risk.
Tenofovir—found in Viread, Truvada and Atripla—has been linked to kidney toxicity in a small number of people using the drug. New research at IAC has determined factors that may put patients at risk for this side effect, including having high blood pressure, using it with PIs and combining it with other meds known to cause kidney problems. But for those using it with a non-nuke as a component of initial therapy—think Atripla among first-time treatment takers—the risk is actually reduced.
Yet more data shows that tesamorelin, an experimental compound from Theratechnologies in Montreal that sparks the production of natural human growth hormone, can reduce deep belly fat in HIV-positive folks with lipodystrophy. And it doesn’t appear to increase the risk of diabetes—a problem with Serono’s growth hormone product Serostim that failed to pass the FDA’s approval review.
A medicinal compound in milk thistle, a flowering member of the daisy family, may benefit liver function in HIV-positive people with hepatitis C, according to a small but intriguing study out of New York City. The researchers hope for a larger study to further explore its potential.
Transmission and Prevention
The push continues for behavioral and biomedical prevention strategies that are proven to work—and can be implemented in all areas of the world where they are needed most. Notable reports from IAC include:
Thousands of more new HIV cases are occurring in the United States every year than was previously believed, according to startling new data from the U.S. Centers for Disease Control and Prevention (CDC). While in Mexico City, POZ’s Regan Hofmann checked in with the CDC’s Kevin Fenton, MD, PhD, about these new numbers and the possibility of a national prevention plan.
Researchers have not yet been able to develop a safe and effective HIV-neutralizing gel or cream to block sexual transmission of the virus—but an emerging crop of microbicides continues to make headway. In a video interview, Zeda Rosenberg, ScD, of the International Partnership for Microbicides, explains the lessons learned in recent microbicide trials and provides a glimpse at what’s next for this important prevention tool.
Results from the first trials of ARVs being tested in HIV-negative people at risk for infection with the virus—a concept known as pre-exposure prophylaxis (PrEP)—are expected to make their debut in 2009. The AIDS Vaccine Advocacy Coalition (AVAC) released a report in Mexico City suggesting that it’s time to seriously plan for PrEP’s arrival. Ian McGowan, MD, PhD, of the University of Pittsburgh, agrees with the AVAC recommendations and, in a video interview with AIDSmeds, reviews the planning and preparations needed.
For HIV vaccine research to move forward, we must first understand why efforts thus far have failed. Seth Berkley, MD, of the International AIDS Vaccine Initiative, talks with AIDSmeds about the challenges researchers have faced and the important next steps.
New research out of Johns Hopkins University shows that a substantial number of HIV-positive women intend to start, or continue having, children. Many of the women, however, were unaware that ARV therapy, when used during pregnancy and delivery, can profoundly reduce the risk of transmitting HIV to the baby, underscoring the importance of treatment education.
The Global Picture
Efforts to make HIV care available to more people living with HIV in the developing world continue to make progress—but challenges are still very much apparent.
Mother-to-child transmission (PMTCT) programs for pregnant women continue to move forward, as was highlighted in a lecture by Alex Coutinho, MD, of Makere University in Kampala, Uganda. About 33 percent of HIV-positive pregnant women were enrolled in a PMTCT program last year—compared with only 10 percent in 2004—which includes access to ARVs to help prevent transmission of the virus during pregnancy and delivery. Children also continue to benefit: In 2005, only 75,000 children in low-income countries had access to ARV therapy, compared with 200,000 in 2007.
Yet only 31 percent of people who need HIV treatment have access to it, and the majority of people living with HIV in developing countries are still unaware of their HIV status. Coutinho noted that most countries will not achieve universal access to prevention, treatment and care by 2010—the latest goal by the World Health Organization (WHO), The Joint United Nations Programme on HIV/AIDS (UNAIDS) and UNICEF.
Universal access to ARV therapy is feasible even in the most rural areas of low- and middle-income countries by using a simple and standardized approach to care, according to a report out of the rural Thyolo district of Malawi, Africa. However, data from a second Malawian study indicate that high-level drug resistance is a major concern among patients no longer responding to their first ARV regimen and may greatly impede their ability to benefit from subsequent regimens.
Another major obstacle: Médecins Sans Frontières (Doctors Without Borders) is reporting a shortage of health care workers in southern Africa. This, the Nobel prize–winning humanitarian organization reports, profoundly impacts efforts to increase access to treatment and care for people living with HIV.
Last but not least is a video interview with Sofia Guskin, JD, of Harvard University. She illustrates how human rights struggles impact the AIDS epidemic but presents evidence that progress is finally being made.
