In the early 1980s, as a physician at the University of California Medical Center, researching and treating sexually transmitted viral diseases, I found myself at the epicenter of an emerging crisis that would define an entire era. San Francisco, a city known for its progressive spirit and diversity, became the unwitting battleground against a deadly adversary we would come to know as acquired immunodeficiency syndrome (AIDS).
I was among the first physicians treating AIDS in the city, setting off a chain of events that would forever change the trajectory of healthcare and public health. As people increasingly began to exhibit the symptoms of this new condition, we soon learned the mystery syndrome was caused by the human immunodeficiency virus (HIV) and that we were in the midst of an emerging HIV/AIDS epidemic. The virus attacks CD4 T cells that help the body fight off infections, making people vulnerable to other infections or diseases that our immune system can usually fight off and ultimately leading to AIDS. More than 85 million people have been infected with HIV and about 40 million have died of HIV globally, since the beginning of the epidemic.
Over the next 35 years that followed, we have witnessed the evolution of HIV from the grim days when it was a death sentence to now being a life-long illness. The progress toward improving the day-to-day health of people living with HIV has been nothing short of stunning. This has been a result of collaborative efforts to increase awareness of the disease, how it spreads, testing, treatment, and preventive care initiatives coupled with our understanding of the virus through medical research.
In the early 1990s, highly active antiretroviral therapy (HAART), a combination of multiple antiretroviral treatments (ART), was developed and made available as the first line of treatment. ART fights back the virus and restores immune function enabling people to live with HIV for far longer than when the epidemic began. The morbidity and mortality associated with HIV dropped significantly with ARTs.
The fight against HIV, however, is far from over. People living with HIV are still facing challenges despite the advancement in ART, including poor adherence and failure of first-line ART.
Treatment adherence is critical to managing HIV and preventing further spread of the virus. This entails starting treatment immediately following testing and diagnosis, being consistent in taking the medication exactly as prescribed and keeping all medical appointments. Skipping medication allows for the virus to multiply, increasing the risk of drug resistance and progression.
Today, we find ourselves confronted with a sobering reality and public health risk: in the U.S approximately 45,000 people living with HIV are clinically failing first-line ART treatment, 91,000 patients are non-adherent for hard-to-address reasons, and the ongoing transmission risk is contributing to 35,000 to 40,000 new infections each year.
What is important to note is that people who fail the first line of treatment are more likely to fail again with second-line drugs as well as experience side effects, treatment fatigue, and potentially drug resistance. Early detection of treatment failure is critical to sustaining the effectiveness of the first line of treatment. The development of drug resistance-associated viral mutations continues to pose a threat to the community because once these mutations are transmitted it may be harder to treat new patients with current medications.
One of the most reported barriers to adherence to antiretroviral therapy is stigma. Because of the long history of stigma and discrimination against people living with HIV, patients may hide the fact that they are taking medications which can lead to inconsistent timing of ingestion or altogether forgetting to take their medication.
People living with HIV who have comorbid mental disorders such as substance abuse and depression have also been found to have poor adherence. Historically high pill burden has also been associated with poor adherence.
Innovation in the HIV treatment landscape is playing a role in addressing medication adherence. In recent years, long-acting injectable antiretroviral monthly and bi-monthly treatment options have been approved – a welcome alternative for people living with HIV.
An HIV cure is one of the ultimate long-term goals of research today, as we strive to go beyond ARTs. This could take the form of a “sterilizing cure”/ “eradication” defined as the removal of all replication-competent virus, or a “functional cure”/ “viral control off therapy” defined as undetectable virus off antiretroviral therapy using a standard clinical assay.
We are now on the cusp of it coming full circle from the days when patients took multiple pills a day to potentially a one-and-done single-dose treatment – unlocking the power of cell and gene therapy.
Having devoted my entire career to treating and now searching for a cure for HIV I am both hopeful and exasperated. Hopeful, because tremendous medical progress has been made. But exasperated, because we have fallen behind on one of the vital tools for controlling the epidemic: adherence to HIV treatment.
We may have dealt with significant setbacks in a decades-long effort to control the global HIV epidemic and lost loved ones along the way. However, early clinical trials of gene and cell therapy have shown promising results. That is why I remain optimistic we are closer than ever to finding a cure.
Photo: Khanisorn Chaokla, Getty Images
