HIV Update from CROI 2023
Stem-Cell Transplants to Combat HIV & Cancer:
We learned additional, promising details about the stem cell (bone marrow) transplant procedure successfully used on a third of now five patients with both HIV and either leukemia or lymphoma. That procedure involves a bone marrow donor whose immune cells are naturally resistant to HIV. This particular PWH (named Marc) who received this treatment in Dusseldorf, Germany and is now termed the “Dusseldorf Patient” has successfully lived HIV-free for over four years without HIV medications. While he has suffered two relapses of his leukemia and minor sides effects form his treatments, he continues to describe himself as doing well.
Important Information about Immune Cells:
A strong and persistent theme in HIV research continues to be an increasingly clearer understanding of what happens to the virus in persons with HIV (PWH) who have received effective treatment for many years. At this year’s conference, Janet Siliciano, PhD, a remarkable laboratory researcher from Johns Hopkins University Medical School in Baltimore, described the trajectory of HIV within four PWH who had received effective HIV treatment for between 10 and 23 years. What her team found was eye-opening.
In contrast to long-held and scientifically based beliefs that, latent (sleeping), inactive HIV embedded in the immune cells of these PWH progressively decays, in fact, it does not, but remains very steady. But why? The most probable reason was not failure of or resistance to HIV medications, but rather a result of proliferation, which is a naturally occurring function of the immune cells (CD4+ T cells) in which HIV resides. These cells naturally increase in number (proliferation), and as they are doing this, they prevent the inactive HIV from decaying.
While there is no new HIV introduced, the existing HIV simply keeps renewing itself. With this new information, new strategies for detecting and halting this HIV-proliferating process in immune cells can, and already have been, developed. Thus, new opportunities for curing HIV are being explored.
Cabenuva ® Injectable Bi-Monthly HIV Treatment:
We heard results from several promising studies on the recently FDA-approved (January 2021), long-acting, two-drug injectable HIV treatment called Cabenuva® (cabotegravir and rilpivirine).
This treatment, which uses two medications, each injected into each buttock muscle once every two months, has continued to show long-term safety and effectiveness in keeping HIV under control. When PWH were asked about their preference for a daily oral pill or one injection every two months, over 95% consistently preferred the injections. Reasons given for this were: no need to remember to take a daily pill or frequently refill prescriptions, easier travel for work or vacation, no need to carry or store medications at home, and freedom from the daily reminder of being HIV+.
A pilot study potentially expanding the use of Cabenuva® to a more challenging group of PWH, presented by Monica Gandhi, MD from UC-San Francisco, demonstrated that 55 of 57 PWH who did not meet the usual requirement of having fully suppressed HIV on oral medications prior to changing to long-acting injectable medications, also achieved well-suppressed HIV. Most of these PWH had advanced HIV illness (AIDS), and were homeless or had unstable housing; 40% were regularly using methamphetamine, and 35% had mental illness. Thus, this new long-acting injectable method of delivering HIV treatment may be an especially useful option for these PWH.
Cabotegravir (Apretude®) Injectable PrEP:
Cabotegravir given alone (Apretude®) was approved by the FDA in December 2021 for use as pre-exposure prophylaxis or PrEP. PrEP is prescribed to persons who are at-risk for acquiring HIV through sex or injection drug use.
- The U.S. National Institutes of Health (NIH) conducted two large international studies, one among gay men and transgender women, the other among cis-gender women who have sex with men. In both studies, cabotegravir was injected once every two months, and was found to be superior to taking a daily tablet of Truvada (the first medication licensed for PrEP in 2012) in terms of preventing new HIV infections.
- One potential concern for using this type of injectable PrEP are delays in receiving the injections, and this was explored in a study of cis-gender, heterosexual women who delayed injections of cabotegravir for up to 14 weeks. The study showed that even with delays in receiving injections, the women were able to maintain effective blood levels of the drug, which correlates with protection from HIV infection. Based on these results, at least among the cis-gender women studied, the schedule for cabotegravir possibly may be adjusted to every three months instead of every two months.
An Even Longer-Acting HIV Treatment in Development:
On the research horizon, Joe Eron, MD from University of North Carolina-Chapel Hill, presented results of a small phase 1 study using a regimen of three ultra-long-acting anti-HIV treatments (each one is dosed once every six months).
In this 21-person study, roughly half of the PWHs were assigned to treatment with lenacapavir, a newly FDA-approved (December 2022) injectable HIV medication also known as Sunlenca®. Along with lenacapavir, all study participants also received two man-made anti-HIV antibodies (bnAbs) called TAB and ZAB, administered at different doses. After six months following injection of lenacapavir and a single infusion of each antibody, 90% of study participants in each group maintained their previous well-suppressed level of HIV. Minor side effects occurred which did not impede treatment.
Imagine an HIV treatment regimen given just once every six months!
Not-So-Good News on the HIV Vaccine Development Front:
We learned about the unfortunate failure of yet another vaccine strategy used in the MOSAICO study. This large, international study conducted among gay men and transgender persons, primarily living in South and Central America and the U.S., was testing a new vaccine strategy against HIV — one very similar to a successful COVID-19 vaccine.
Regrettably, while the vaccine was safe and well-tolerated among those who received it compared to a placebo-receiving group, it showed no evidence of protection from acquiring HIV. A compelling discussion lead by HIV vaccine expert Larry Corey, MD from University of Washington – Seattle, pointed out the newly-discovered flaws and limitations of the failed vaccine strategy, which will lead to a more informed approach going forward.
STI Reduction Using Doxycycline:
In an attempt to address the steadily rising number of new cases of sexually transmitted infections (STIs) — notably syphilis, chlamydia and gonorrhea, especially among persons taking PrEP for HIV — several studies studied the use of a commonly used, oral antibiotic called doxycycline (200mg) as post-exposure prophylaxis or PEP (“doxyPEP”). This means that one takes the antibiotic within 72 hours of possible exposure to the STI by a condomless sexual encounter.
- Jean-Michelle Molina, MD from Paris reported results from a DoxyPEP/DoxyVAC study of gay and bisexual men, most of whom were also receiving Truvada as PrEP for HIV. Study participants were randomly assigned to take (a) DoxyPEP alone; (b) vaccine alone [(meningitis B vaccine 4CMenB (Bexsero)]; or (c) both DoxyPEP and the vaccine. The two bacteria which cause gonorrhea and meningitis B are closely related; therefore, using the approved vaccine against meningitis B was being studied for its potential protective effects against gonorrhea.The results of the study showed that, compared with no regimen of doxycycline or meningitis B vaccine, DoxyPEP was able to reduce cases of chlamydia by 89%, cases of syphilis by 79%, and cases of gonorrhea by 51%. Interestingly, administration of the meningitis B vaccine led to a 51% reduction in new cases of gonorrhea.
- However, a similar study provided a stark contrast in results. Jenell Stewart, MD of Hennepin Healthcare in Minneapolis, evaluated a Paris study of cisgender women in Kenya taking Truvada for PrEP for HIV. After being administered DoxyPEP, the women (who had similar rates of STIs to Kenyan men) showed no reduction in the occurrence of chlamydia, syphilis or gonorrhea.Possible, but unconfirmed, reasons for this different result may be anatomical differences between male and female genital tracts, pre-existing resistance to doxycycline, and inadequate compliance with the doxycycline regimen.
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All-in-all, CROI 2023 reminded me of this conference’s high value for advancing our knowledge about HIV, improving methods to treat and prevent it, and unearthing new strategies for a potential cure for HIV.