The Human Immunodeficiency Virus (HIV) is a global pandemic, with 39 million cases worldwide, and over 1 million new infections each year. While it rose to epidemic and then pandemic levels in the 1980s, the first case goes back to 1959. HIV is a retrovirus that inserts its genetic material into the DNA of host cells, and targets the immune system as a “preemptive strike”, leaving those infected susceptible to opportunistic infections and cancers.
It has also been the target of a global effort to treat and prevent new infections, with fairly steady success over the last four decades. HIV is now manageable as a chronic illness, and effective treatments have lead the WHO to declare a goal to reduce new infections to zero by 2030. At the same time HIV has been the target of considerable pseudoscience, including denial that it exists and causes AIDS, that it was manufactured as a government conspiracy, and that there are numerous “alternative” treatments for HIV.
HIV has therefore been an interesting microcosm of the struggle between science and pseudoscience in tackling serious disease. It is helpful to look back over the history of this struggle – because there has been a clear victor. The proclamations and predictions of the deniers, alternative medicine gurus, conspiracy theorists, and pseudoscientists have all come to nothing. Meanwhile scientists have dissected HIV down to its core and devised numerous effective treatments.
We can now add one more victory for science against HIV – a preventive treatment that shows an astounding 100% efficacy in a phase III clinical trial. The treatment, lenacapavir, is a new PrEP strategy (pre-exposure prophylaxis) trialed in women in South Africa and Uganda. The treatment was compared to existing PrEP treatments, and was deemed so effective the trial was stopped early so that participants could choose to go on the new treatment.
Existing PrEP pills include:
- Truvada® (emtricitabine/tenofovir disoproxil fumarate) is for all people at risk for HIV through sex or injection drug use. Generic versions are also available.
- Descovy® (emtricitabine/tenofovir alafenamide) is for sexually active men and transgender women at risk of getting HIV. Descovy® is not for people assigned female at birth who are at risk for HIV through receptive vaginal sex.
There is also Apretude® (cabotegravir), an every other month injection.
These treatments are about 99% effective in preventing infection, if used correctly. The tenofovir treatments are replication inhibitors. They are incorporated into HIV’s DNA where they stop replication. Cabotegravir binds to the enzyme integrase, which is necessary for the virus’s DNA to integrate into host DNA.
The “if used correctly” caveat is critical. The daily pills must be taken daily, and take between 7 and 21 days to achieve full efficacy. Taking a daily medication without exception can be challenging for many at-risk populations. Preventive strategies are best evaluated by “intention to treat” analyses. It is certainly necessary to demonstrate efficacy – that the treatment actually works. But it is also necessary to demonstrate effectiveness as a prevention strategy. If the drug works but few people take it for whatever reason, it’s not very effective.
The new treatment, lenacapavir, is given as an every six month injection. This is potentially a huge advantage, as one treatment provides six months of protection. The recent clinical trial, Purpose 1, compared lenacapavir to the two tenofovir treatments in a double-blind fashion. They found:
“During the randomised phase of the trial none of the 2,134 women who received lenacapavir contracted HIV. There was 100 percent efficiency.
By comparison, 16 of the 1,068 women (or 1.5%) who took Truvada (F/TDF) and 39 of 2,136 (1.8%) who received Descovy (F/TAF) contracted the HIV virus.”
Zero cases out of 2,134 women is impressive. I tried to find out how long a period this was, but the data is given per 100 person years. This is not helpful when the incidence is zero. But the methods indicates follow up for at least 52 weeks. Further, young women were studied because they are considered a very high risk population in these countries.
The fact that lenacapavir is 100% effective and is convenient, as a twice yearly injection, is significant. The pharmaceutical company, Gilead Science, says they will make the drug available to generic producers, which should keep the price down. This will hopefully make it affordable for countries to then provide the drug for free or at very low cost to their populations. It is certainly cost effective to prevent an HIV infection rather than treat HIV for decades.
In a way science has done its job, now it is up to the WHO and world governments to do their job. The goal of reducing new HIV infections to zero by 2030, while difficult, is not unachievable. It even raises the possibility of eventual elimination. It will be hard to eradicate as there are animal reservoirs, but cross-species infections are likely to be rare.
This is all great news. It is also important to step back and see the big picture. Science has steadily delivered and has given us the tools to fight this virus and possibly eliminate it. Pseudoscience has given us literally nothing, and has only served to delay and confound proper treatment.
