Developing new treatment regimens for HIV

Since the HIV epidemic began in the early 1980s, more than 85 million people have been diagnosed worldwide and about 40 million have died as a result of complications from the virus.¹ Now, four decades later, 39 million people around the world are living with HIV, primarily due to advances in treatment.¹ With continued innovation on the horizon in terms of prevention and treatment methods, what was once a wishful hope of ending the epidemic has become a conceivable goal.

HIV treatment and prevention are at an inflection point after years of continuously improving the standard of care of once-daily oral medicines. Our industry is on the cusp of the next wave of medicines that will guide the coming decade of HIV care, making HIV a smaller part of people’s lives. In just the past three years, we have seen a shift of focus to longer-acting options. Future innovation will be defined by ultra-long-acting options, self‑administration and, hopefully, concrete steps toward a cure.

Reducing HIV treatment burden and stigma

Decades of pharmaceutical advances and an array of treatment and prevention options mean that many people living with HIV can expect to live longer and fuller lives. In fact, a study published in 2023 in The Lancet HIV revealed that women and men with HIV at age 40 had an average of 39 and 37 years of life left, respectively – only a few years less than that of the general population – if they started antiretroviral therapy (ART) after 2015.²

However, despite industry advances in treatment and prevention, HIV continues to be marked by intense social stigma, rooted in fear and misconceptions that persist from the epidemic’s early days. Self-stigma is also prevalent and hinders individuals from getting tested, starting pre‑exposure prophylaxis (PrEP) (if they’re HIV negative), seeking the lifesaving treatments they need (if they’re HIV positive), and can lead to isolation and depression.³ While gone are the days when an HIV diagnosis necessitated taking so many pills that patients had to set multiple alarm clocks, self-stigma and concerns of external stigma still exist. They often arise when taking daily pills, causing fear of HIV status disclosure, stress and anxiety about staying adherent, and the constant reminder that the individual is living with HIV.³

But that paradigm is rapidly changing. Through research and development, there is potential for options that reduce the number of times maintenance medicines need to be taken to suppress HIV as well as reduce the number medicines taken over an individual’s lifetime. These steps can help lessen the impact of HIV stigma by allowing many people to have a choice in treatment options.

Where we are going

While longer acting regimens have transformed the HIV treatment landscape for many people living with the virus, our work to end the epidemic will not stop. Achieving an undetectable viral load should be the starting point for an HIV treatment. For individuals living with HIV, feeling like their life is not dictated by the disease is what the industry is working towards. Through direct engagement and collaboration with the HIV community – people who live with HIV, their providers and those who support them, along with people who want to prevent acquiring HIV – we know more is needed. Individuals with HIV who adhere to their ART regimens can successfully achieve undetectable levels of the virus in their blood and eliminate the risk of disease transmission; however, they must remain on treatment to maintain suppression of HIV.

Analysis reveals “superior efficacy” of long-acting injectable HIV treatment

These insights are leading to further, meaningful innovation, currently underway in the form of ‘ultra long-acting’ treatment and prevention options, along with at-home self-administration treatment options. In the coming years, the goal is for HIV medicines to be taken in intervals that allow at least three or four months between doses, as well as the ability to take them in the privacy of home as opposed to a health clinic. Beyond the potential to provide disease suppression on par with current regimens, many people living with HIV say this would also help reduce the emotional toll and reminder of their HIV status that can come from taking a daily treatment.

Having clinical trial designs focused on diversity is important.

Innovation will also extend beyond treatment duration and encompass the targets we attack to fight the HIV lifecycle in the human body. For more than 15 years, integrase strand transfer inhibitors (INSTIs) have served as the foundation of ART regimens in HIV treatment guidelines around the world and our present portfolio is built on them. While our research for next-generation long-acting regimens has INSTIs at their core, research will also look at other novel mechanisms of action that can attack various targets across the HIV replication cycle.

For example, broadly neutralising antibodies (bNAbs), capsid inhibitors and maturation inhibitors all might play a role in fighting HIV from the initial binding and fusion of HIV into immune cells, to where it integrates into the cell, out to its assembly and maturation.

We know that developing more treatment and prevention options are essential to tackling the still pervasive HIV epidemic. But that in itself is not enough when considering the spectrum of populations that require these medicines. Having a strong focus on recruiting diverse clinical trial participants along with additional implementation science studies can help industry bridge the gap between research findings and delivery of these different options. Having clinical trial designs focused on diversity – including a deep understanding of the demographics where HIV has the greatest impact – is critical to reduce biases, promote social justice and health equity and produce more innovative science. Most importantly, this will allow us to better identify what works best, why it works, and how findings can continuously be applied to improve the lives of anyone with HIV, regardless of race, ethnicity and socioeconomic status, among other variables.

Finally, advances in therapies that reduce viral load and ease the treatment burden for patients are exciting, but they will not distract us from our end game – a cure for HIV. What was once seen as a hopeful dream decades ago, now promises to be a realistic opportunity for people living with HIV. The core of our cure strategy is focused on identifying dormant HIV that may be hiding in human cells undetected by the immune system or HIV treatment. Once identified, the idea is to drive this virus out of hiding with medication so that it can be eliminated and then harness the body’s own immune responses against rebounding virus. As the only company completely focused on HIV, we are well aware that every resource we invest in researching a cure for HIV is an investment in putting our company out of business. It’s emblematic of our commitment to be here until HIV and AIDS are not.

The decade ahead

As we move through the decade, we anticipate driving a fundamental shift in how HIV is treated and prevented with ultra long-acting options. This will signal a major market shift from the past, which has been dominated by daily regimens, to a landscape that offers a variety of longer acting options that can be taken less frequently and delivered in new ways. We view this shift as being key to meeting the evolving needs of people living with HIV and those who may have reasons for HIV prevention, who expect new options to make HIV a smaller part of their lives.

As we advance these ultra long-acting options through clinical research and regulatory approval, we will not lose sight of our promise to leave no person living with HIV behind. 

References

1. World Health Organization. The Global Health Observatory. HIV. [Internet] 2023. [cited 2024Jan] Available from: https://www.who.int/data/gho/data/themes/hiv-aids
2. Trickey A, Sabin CA, Burkholder G, et al. Life expectancy after 2015 of adults with HIV on long-term antiretroviral therapy in Europe and North America: a collaborative analysis of cohort studies. Lancet HIV. 2023;10(5):e295-e307.
3. The Positive Perspectives Survey Report. [Internet] 2017. [cited 2024Jan] Available from: https://edgesuite.gskstatic.com/Viiv/viivhealthcare/pdf_files/master/main/positive-perspectives-survey-report-finalcompressed.pdf.