CLINICAL MATTERS
Every year on December 1 is World AIDS day, during which people from around the world come together to raise awareness about HIV and AIDS and demonstrate international solidarity against this deadly disease. It has been 40 years since the virus that causes Acquired Immune Deficiency Syndrome (AIDS) was identified and isolated. In that timespan, the remarkable advances in the prevention, treatment, and control of HIV have been nothing short of lifesaving. Prior to the discovery of effective antiretroviral treatment, a diagnosis of HIV was akin to a death sentence. It takes eight to 10 years from infection to develop full-blown AIDS. Once the symptoms of opportunistic infections start to manifest, however, most people die within a year. Prior to the discovery of effective treatment, millions of young people were cut down by HIV in the prime of their lives. In parts of the African continent, entire villages lost their young adult populations, resulting in grandmothers and grandfathers taking care of their grandchildren, some of whom were infected with HIV from their mothers.
The horror of the early days of the AIDS pandemic is slowly fading into memory. For those who lived through it, these were no less frightening than the early days of the COVID-19 pandemic. In the United States, young men in San Francisco were dying from rare pneumonias and cancers from what was then misguidedly termed GRID or gay related immunodeficiency disease. This awful terminology foreshadowed the extreme stigma attached to this infection. The race was on to find the cause of the malady. Eventually, researchers at the Pasteur Institute in France were able to isolate a new virus that eventually became known as HIV. It took more than ten years to finally develop effective treatment, then termed highly active antiretroviral therapy (HAART, or ART for short). Consisting of a combination of three drugs, ART revolutionized the treatment of HIV and kept those infected with HIV alive for years. As more potent agents with less side effects were discovered, early treatment with ART nearly normalized life expectancy, leading to the more appropriate term “people living with HIV (PLHIV)” to refer to people infected with the virus.
Early in the 2000s, the use of ART for all PLHIV regardless of stage of disease was still being debated. Given the cost and the side effects of the available drugs at that time, many doctors felt that HIV had to be sufficiently advanced to justify the drawbacks of lifelong medication. As more data was gathered and ART regimens became better tolerated, it became apparent that starting ART on all PLHIV was the correct thing to do. Recognizing the value of adherence in ensuring the successful treatment of HIV, three-in-one once a day pills were developed which greatly simplified ART treatment. Unfortunately, the virus was still able to mutate and develop resistance in those who weren’t adherent to treatment and these drug-resistant viruses were transmitted. With very limited capacity to test for drug resistance in many parts of the world, drug-resistant HIV quickly spread. This has resulted in resistance rates of more than 20% to first line drugs such as efavirenz in treatment-naïve individuals in some countries.
Recognizing this concerning increase in HIV drug resistance, the World Health Organization decided to update its recommended antiretroviral agents with newer, more durable drugs. Dolutegravir, an integrase strand transfer inhibitor (INSTI), was used to replace efavirenz as the recommended first-line treatment in combination with two other nucleoside reverse transcriptase inhibitors (NRTIs). Through negotiations with the manufacturers of these drugs, the price for these medications in resource-constrained settings was drastically lowered and made available to those who could not otherwise afford them. In the Philippines, dolutegravir-based regimens are now the standard of care and are expected to be more durable than efavirenz-based regimens with fewer side effects.
This shift to better first-line medication is timely as research from the University of the Philippines National Institutes of Health has shown that the rate of HIV drug resistance in newly diagnosed PLHIV in the Philippines is high at 11.7 percent. New regimens incorporating long-acting injectable ARVs such as monthly and bimonthly cabotegravir and rilpivirine combinations have successfully completed clinical trials and have further simplified the treatment of HIV. We hope that these long-acting regimens, along with additional durable second-line drugs such as darunavir can be made available to our Filipino PLHIVs as part of our nationwide HIV and AIDS response.
ART, when taken correctly and in the absence of resistance, decreases the amount of virus in the blood of PLHIV to undetectable levels. Subsequent research has shown that those who achieve viral suppression are no longer able to transmit the virus to others. This incredible finding is behind the U=U campaign, which stands for undetectable equals untransmittable.
This means that a PLHIV who is on ART and has a viral load of less than 200 copies/mL can safely have children the natural way without risk of infecting his or her partner and child. This also means that a doctor living with HIV can safely operate on patients without risk of infecting them. Most importantly, U=U means that if we can find and successfully treat every single PLHIV, then we can realistically aim for zero new infections.
Another recent innovation is pre-exposure prophylaxis, also known as PrEP. This is typically two ART drugs, usually a combination of tenofovir and emtricitabine, taken either daily or in an event-driven manner for those who are at high risk for HIV infection. Properly used, PrEP decreases the risk of HIV infection by up to 99 percent. Recently, following the success of long-acting ART, long-acting injectable PrEP given every 60 days has been approved in some countries. This consists of a single drug, cabotegravir, and WHO has recommended its use as an additional option for PrEP.
The quest for a practical HIV cure remains elusive. While five people seem to have achieved a true sterilizing cure for HIV, these cures were achieved as a result of bone marrow transplants to treat cancer. It is too risky to routinely use bone marrow transplants to cure HIV, and there is no guarantee it will work as only a handful of PLHIV with cancer who underwent this procedure achieved cure. However, the fact that a cure is possible has galvanized researchers and the search goes on.
On the local front, Filipino scientists continue to work on studying our local HIV epidemic and looking for solutions to improve care. Molecular epidemiology work from our laboratory at the UP-NIH has shown that the unprecedented increase in HIV cases is at least driven by a shift in subtype from B to a more aggressive and transmissible CRF01_AE. Our portable HIV drug resistance test funded by the Department of Science and Technology won innovation of the year in a prestigious international competition and is slated to begin clinical trials next year.
The innovations of the last 40 years have transformed HIV from a fatal disease to a manageable and treatable one. Even without an effective vaccine or a practical cure, the means currently exist to eliminate HIV and usher in an AIDS-free generation. Achieving these goals is only possible if we all come together as a nation to combat stigma, educate our people, and use all our innovative tools to stop HIV in its tracks.