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HIV: Advances in Treatment

  • Chris Woolston. M.s.
  • Posted March 11, 2013

For all of the progress made against HIV/AIDS over the years, the push for still better treatments is far from over. Until a cure is discovered, doctors and researchers will continue to look for new and more effective ways to control the disease and save lives. While HIV medications can attack the virus and keep the disease in check for several years or more, the side effects can be severe, the medications can be difficult to take, and they don't always work for everyone. Fortunately, some key advances in recent years have made treatments easier, safer, and more effective.

New medications

Patients who aren't getting better despite aggressive treatment have new hope for recovery. Researchers are developing drugs that work in entirely different ways from the first generation of HIV medications. In 2007, the U.S. Food and Drug Administration (FDA) approved maraviroc (Selzentry), a drug known as an "entry inhibitor." Doctors also call it a CCR-5 co-receptor antagonist. Unlike earlier HIV medications that keep the virus from dividing after it enters a white blood cell, maraviroc can stop the virus from entering the cells in the first place. The drug blocks the main entryway into cells. Because different strains of HIV use different entryways, the drug will not work in all cases. Blood tests can show if your particular strain of HIV will respond to this drug.

Studies have found that the drug was able to reduce levels of HIV and boost the immune system of patients who weren't responding to other drugs. Over time, however, it may cause liver damage and raise the risk of heart trouble. Less serious side effects can include cough, fever, colds, rash, abdominal pain, dizziness, and muscle pain.

The year 2007 saw many firsts in HIV treatment. It was the year the FDA approved raltegravir (Isentress), the first drug in a class known as integrase inhibitors. It works by keeping the HIV virus from inserting its genetic material into white blood cells. Like maraviroc, the drug can reduce virus levels and increase immune system cells in patients who aren't responding to other drugs. The most common side effects seen during studies include headache, fever, diarrhea, and nausea.

In addition to creating whole new classes of drugs, researchers continue to improve on old types. In 2007, the FDA approved etravirine (Intelence), a non-nucleoside reverse transcriptase inhibitor that blocks an enzyme the virus needs to copy itself. When used in combination with other HIV drugs, etravirine can reduce levels of HIV in the blood while boosting levels of germ-fighting white blood cells. One major downside to the drug is that it can cause mild to severe skin rashes. The rashes sometimes disappear within a few weeks, but not always. If you're taking this drug, be sure to tell your doctor if you notice any sort of rash. Other common side effects include nausea, nerve pain, diarrhea, stomach pain, vomiting, fatigue, headache, and high blood pressure.

In 2006, the agency simplified treatment for many patients by approving Atripla tablets, which combine three common HIV drugs (efavirenz, emtricitabine, and tenofovir disoproxil fumarate) into one pill. A study lasting just under one year showed that the combination pill reduced the virus and enhanced the immune system of 80 percent of HIV patients. Unfortunately, the pills can also cause mental problems, including suicidal thoughts, confusion, hallucinations, memory loss, aberrant thinking, paranoia, and depression. Patients should also watch out for warning signs that the drug is damaging the liver or the muscles. If you're taking Atripla, tell your doctor about joint pain, muscle pain, shortness of breath, dizziness, stomach pain along with nausea or vomiting, loss of appetite, yellow-colored skin, pale stools, or dark urine.

Faster treatment, better results

New drugs are just one part of the ongoing fight against HIV. Researchers are also continually looking for the best ways to put current drugs to use. A major study published in the New England Journal of Medicine (NEJM) in 2009 may change the approach to treating HIV. The study followed more than 17,500 patients with HIV infections that had not yet caused any symptoms.

Researchers used a measurement called a "CD4+" count to classify each patient based on the strength of his or her immune system. Patients were then divided into two different groups: those with CD4+ counts of 351 to 500, and those with counts higher than 500. Within each of the two groups, patients either began early treatment with antiretroviral drugs or deferred treatment until their CD4+ counts dropped below 350 or 500, respectively. The researchers found that those who received early treatment had a significantly better survival rate.

The study suggests that patients with a CD4+ count between 351 and 500 and even higher should get treatment right away. Compared with patients who got treatment immediately, patients who waited until their count dropped below 350 to start taking medications -- the usual approach -- had a 69 percent greater mortality risk. Patients who received treatment while their CD4+ count was still above 500 fared even better. Compared with these early starters, patients who followed the usual treatment plan had a 94 percent greater mortality risk.

Another study published in January 2008 pointed toward even more potential benefits from early therapy. As reported in the Journal of Acquired Immune Deficiency Syndrome, starting treatment when the CD4+ count is above 350 seems to reduce the risk of anemia and painful nerve damage (neuropathy).

Advances in prevention

The ultimate goal for many HIV researchers is finding a way to stop the infection before it starts. Ever since the early days of the epidemic, doctors have envisioned a vaccine that could make people invincible to the virus. Just as vaccines rid the world of smallpox and nearly erased polio, it was hoped that a simple shot could make HIV a thing of the past.

Researchers continue to pursue a vaccine for HIV, but the goal remains elusive. Vaccines work by preparing a person's natural immune system to fight a particular germ. As noted in a 2008 issue of the NEJM, the search for an HIV vaccine is greatly complicated by the fact that the human immune system has very few defenses against the virus. Still, researchers have recently completed testing a two-vaccine regimen in Thailand. On September 24, 2009, a team of U.S. and Thai researchers announced that their investigational vaccine regimen was safe and 31 percent effective in preventing HIV infection. Although this appears to be a modest result, it was "the first time an investigational vaccine has demonstrated some ability to prevent HIV infection among vaccinated individuals," says Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases. "Additional research is needed," he adds, "to better understand how this vaccine regimen reduced the risk of HIV infection." According to the NEJM report, it may never be possible to completely prevent HIV infection with a vaccine. A successful vaccination may only be able to slow the spread of the virus once it enters the body. Even that, of course, could be a life-saving advance.

Nevertheless, scientists continue to look for new modalities to develop the elusive vaccine. In 2010, at least eight human antibodies were discovered that can stop the HIV virus from infecting cells in a laboratory. Scientists at the National Institute of Allergy and Infectious Diseases discovered that two of these antibodies can block more than 90% of known global strains of the virus. Learning how the structure of the antibody binds to the virus will take the team one step closer to designing a vaccine that could stimulate healthy people to make these antibodies as protection against HIV infection.

Two other milestones emerged in 2010, advancing the hope of effective prevention. While neither milestone falls into the category of a single shot vaccine, both show promise towards controlling the pandemic. One study, published in the November 23, 2010 issue of the NEJM, found that among men having sex with men, a daily dose of an oral antiviral drug reduced the risk of HIV infection by 44%. For those participants who strictly followed the daily regimen, their risk shrunk even further. Close adherence to the daily dosing schedule was 73% effective in reducing the risk of HIV infection.

Lastly, there's new hope that a germ-killing gel could protect women from HIV. In 2010, researchers with the National Institutes of Health reported that a study conducted by the Centre for the AIDS Programme of Research in South Africa (CAPRISA) found that women who regularly used a vaginal microbicide gel made from the antiretroviral drug Tenofovir lowered their risk of contracting HIV through sex by about 40 percent compared with women using a placebo gel. The gel is much less effective than a condom, but not all men are willing to use condoms. Researchers hope that an improved version of the gel could someday give women the chance to put real protection in their own hands.

References

National Institute of Allergy and Infectious Diseases. NIAID Media Availability. Landmark Discoveries Characterize NIH HIV/AIDS Research in 2010. November 29, 2010

Kitahata, M.M. et al. Effect of early vs deferred antiretroviral therapy for HIV on survival. New England Journal of Medicine. April 1, 2009.

U.S. Department of Health and Human Services. Anti-HIV gel shows promise in large-scale study in women. February 9, 2009.

U.S. Food and Drug Administration. FDA approves new HIV drug after priority review. January 2008.

National Institutes of Health. AIDSInfo. U.S. Department of Health and Human Services. Raltegravir.

U.S. Food and Drug Administration. Approval of etravirine for treatment-experienced adult patients.

U.S. Food and Drug Administration. FDA approves the first once-a-day three-drug combination tablet for treatment of HIV-1.

Johnston, M.I. and A.S. Fauci. An HIV vaccine -- challenges and prospects. New England Journal of Medicine. August 28, 2008. 359:888-890.

U.S. Food and Drug Administration. Approval of maraviroc, CCR-5 co-receptor antagonist for treatment of HIV. 2007.

National Institute of Allergy and Infectious Diseases. NIH News, September 24, 2009. HIV vaccine regimen demonstrates modest protective effect in Thailand clinical study.

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