Several major scientific breakthroughs in HIV prevention and treatment in the past 40 years have successfully transformed HIV from a near-certain ‘death sentence’ to a manageable chronic disease where many patients can still enjoy long and largely healthy lives. This, however, is contingent on them having access to the full range of the options available.
A few years after the first AIDS cases in the early 1980s, the first approved treatment for HIV – AZT (Zidovudine) – came in 1987. AZT, a nucleoside reverse transcriptase inhibitor, worked by inhibiting an enzyme crucial for HIV replication. Despite its effectiveness, AZT had severe side effects for patients, including anaemia, and required frequent dosing. Initially, the drug was administered every four hours, around the clock, which meant taking it six times a day; an incredibly burden for patients.
In the 1990s, the introduction of combination therapy, known as HAART (Highly Active Antiretroviral Therapy), revolutionized HIV treatment. By combining multiple drugs, usually three, HAART significantly reduced viral loads and improved life expectancy. The side effects varied depending on the drugs used but included issues like nausea, lipodystrophy, and cardiovascular problems.
Today, almost 30 million people globally are on ART, and José Zuniga of IAPAC describes its advent as “a gamechanger; anyone who has access to ART and maintains optimal adherence can be guaranteed a near normal lifespan.” He adds, “Properly supported to remain engaged in care and adhere to their ART regimens, people living with HIV who achieve an undetectable viral load pose no risk of transmitting HIV, which is an added preventative benefit known as treatment as prevention, or U=U (Undetectable equals Untransmittable).”
The 2000s saw significant advancements with drugs like Truvada (Tenofovir/Emtricitabine), approved in 2004 for both treatment and pre-exposure prophylaxis (PrEP). Truvada, which inhibits reverse transcriptase, was well-tolerated but could cause kidney issues and bone density loss. Another milestone was the approval of integrase inhibitors like Raltegravir in 2007, which blocked the integrase enzyme, preventing viral DNA from integrating into the host genome, with mostly gastrointestinal side effects.
In the 2010s, PrEP with Truvada, approved in 2012, dramatically reduced HIV transmission rates, offering prevention with minor side effects and today forming what AVAC’s Mitchell Warren calls “a cornerstone of the HIV response.” Single-tablet regimens like Atripla combined three antiretrovirals into one daily pill, simplifying treatment and improving adherence, though they sometimes caused vivid dreams and mood changes.
The 2020s saw the introduction of long-acting injectables such as Cabotegravir and Rilpivirine, approved in 2021. These injectables, administered once every one or two months, freed patients from daily pills, with injection site reactions being a common side effect. Dovato (Dolutegravir/Lamivudine), approved in 2019, reduced the number of medications needed, lowering the risk of side effects and drug interactions while maintaining efficacy, with insomnia and headaches being the most noted side effects.
From early treatments requiring strict adherence and having significant side effects, to modern therapies offering simplified regimens and better quality of life, the advancements in HIV treatment and prevention have dramatically improved health outcomes and lifestyle freedom for people living with HIV. As detailed in the ‘Breakthrough Innovation’ article, the bulk of pharma’s HIV R&D efforts are now being directed towards further reducing the burden on PLHIV via an even greater simplification and reduction of the number of pills and injections needed.
Additionally, beyond medicines, several other discoveries have been made, including that consistent condom is associated with an 80% reduction in HIV transmission among couples where one partner is HIV-positive and the other is HIV-negative (2002) and that voluntary male circumcision can reduce the risk of heterosexual men acquiring HIV by approximately 60% (2006).
