Is the focus on HIV treatment distracting from the search for a cure?
The introduction of combination anti-retroviral therapy (ART) in 1996 dramatically reduced the severity and high mortality rate associated with HIV infection and yielded the added benefit of reducing mother-to-child transmission during pregnancy. Each “class” of antiretroviral drugs in the cocktail targets a different step of the virus’s replication cycle. So, in much the same manner as defeating an enemy by attacking on multiple fronts, using a combination of anti-HIV drugs proved to be highly effective at blocking HIV from spreading within the body.
Within the last 10 years, two new classes of anti-retroviral drugs that target additional stages of the virus’s life cycle have been approved, bringing the total arsenal of antiretroviral drugs against HIV to 30 different compounds. But while ART has been wildly successful in the developed world, it was not until 2003 that programs were put in place by the World Health Organization (WHO) to subsidize and distribute ART to people in low- to middle-income countries. Through these programs, free ART was made available to patients who were categorized under WHO guidelines as having immune deficiency, which meant that only those patients with advanced stages of the disease qualified for ART — and, consequentially, infection rates continued to rise.
The number of people receiving therapy has however risen from 400,000 in 2003 to an estimated 6.6 million people by the end of 2011. This accounts for the 42% of people in developing countries who qualify for ART, but is still far from the “universal access for all” ideal proposed by the WHO. The proposal stemmed from a new awareness about the importance of and urgency for universal access after a recent nine-nation study, which demonstrated that HIV transmission to uninfected partners was reduced by 96% when HIV+ individuals are immediately started on ART and adhere to their drug regimens.
In a press conference last Friday, United Nations AIDS agency executive director Michael Sidibe announced his intention to push universal access to the top of the agency’s agenda. He stressed that access to ART is critical to halting the spread of HIV: “Anti-retroviral therapy is a bigger game-changer than ever before- it not only stops people from dying, but also prevents transmission of HIV to women, men and children.” The UNAIDS agency estimated that $22-24 billion would be needed to fund their goal of “zero new infections, zero stigma and zero AIDS-related deaths.”
While we should embrace the initiative to give universal access to ART, we should be cautious in believing this will halt the spread of, let alone eradicate, the HIV/AIDS epidemic. Other than the high cost of universal access, which will inevitably amount to more than the estimated $24 billion, other obstacles exist that may impede the goal of reducing transmission rates. Chief among these is failure of patients to comply with their drug regimens. The side effects of ART can be quite severe and include metabolic disorders, cardiovascular complications, and organ dysfunction. Total compliance with drug therapy has been shown to reduce the rate of HIV transmission by more than 90%. But when confronted with unpleasant side effects, some patients skip doses or discontinue treatment altogether. Worse yet, non-compliance on a large scale could give rise to drug-resistant strains of HIV, which would render current treatment strategies obsolete.
And while ART reduces viral loads to almost undetectable levels in the blood of HIV patients, if the therapy is halted, the virus quickly rebounds to the levels seen prior to the initiation of therapy. This has led researchers to believe that HIV continues to replicate in reservoirs deep within the body — which may explain why even people on ART can eventually develop AIDS.
This brings up a couple of critical points that temper enthusiasm for a program that focuses all but exclusively on the widespread distribution of ART. First, though ART has allowed people to live longer without developing AIDS, it still in some cases only delays immunodeficiency, with additional complications arising from therapy itself. Second, the most cost effective measure to halt the spread of HIV/AIDS would be the development of an effective vaccine or curative therapy. While the access-for-all-initiative will likely improve quality of life for people living with HIV and decrease transmission rates, we should also take note of its potential limitations and high cost. But we must not lose sight of the continuing urgency to develop an effective vaccine or curative therapy — or at least therapies with fewer detrimental side effects.
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