The 24th International AIDS Conference (AIDS 2022), which runs from July 28 through August 2, features hundreds of presentations highlighting the latest science on a wide array of HIV-related subjects. Here we share bite-sized summaries of studies selected by our team of editors and correspondents that provide new data related to HIV cure/remission cases, acceptability of long-acting antiretroviral therapy (ART), and the treatment of coinfections in people living with HIV (PLWH).
Latest HIV Remission via Stem-Cell Transplant Features 63-Year-Old Recipient
We may be able to welcome a fourth individual into what remains one of the world’s most exclusive clubs: individuals whose HIV appears to have been driven into antiretroviral therapy (ART)–free remission, thanks to a stem-cell transplant.
An unnamed individual dubbed the “City of Hope patient”—named after the hospital in Southern California where the procedure took place—has remained free of intact, replicating HIV since discontinuing ART in March 2021, roughly two years after receiving an allogenic stem-cell transplant to successfully treat his acute myeloid leukemia (AML). The donor’s CD4 cells possessed a rare genetic mutation, homozygous CCR5 delta 32, that renders them impervious to infection by most strains of HIV. (This approach was also successfully used in the three prior HIV remission cases that have been widely reported to date.)
The recipient’s age appears to set this instance of HIV remission apart from prior cases: Now 66 years old, the City of Hope patient was 63 at the time of his stem-cell transplant, easily making him the oldest member of the small group of people to achieve sustained HIV remission in this manner. (“Berlin patient” Timothy Ray Brown was 40, “London patient” Adam Castillejo was in his mid-30s, and the anonymous “New York patient” has been categorized as middle-aged.) He had been living with HIV for more than 31 years.
The procedure otherwise appears to be of a kind with the allogenic stem-cell transplants that Brown, Castillejo, and the New York patient received. Unlike these individuals, however, the City of Hope patient did not receive standard full-dose chemotherapy and immunosuppressive treatment before his transplant due to concerns around his age and fitness; instead, he received three courses of a reduced-intensity chemotherapy treatment with a minimally immune-suppressive profile.
In addition to achieving AML remission, repeated testing of the patient’s peripheral blood mononuclear cells (PBMCs) and gut cells have revealed no trace of HIV DNA since 27 weeks post-transplant, and no trace of HIV RNA since he ceased ART at 108 weeks post-transplant.
A more in-depth story on this case will be published on TheBodyPro soon.
Study information: Jana Dickter et al, “The ‘City of Hope’ Patient: prolonged HIV-1 remission without antiretrovirals (ART) after allogeneic hematopoietic stem cell transplantation (aHCT) of CCR5-Δ32/Δ32 donor cells for acute myelogenous leukemia (AML).”
New HIV “Functional Cure” Case Yields More Clues, but Few Firm Answers
The curious case of an older woman who has maintained “exceptional post-treatment HIV control” testifies to how much we have learned about this highly uncommon occurrence—and how much we have yet to understand.
This particular mystery centers around an unnamed woman in Spain who was diagnosed with HIV at age 59, started ART with a baseline CD4 count of roughly 800 cells/mm3 and a viral load of approximately 70,000 copies/mL (suggesting acute infection), and then subsequently stopped ART as part of a pilot study exploring the potential viability of immune-based therapy in reducing a person’s viral reservoir.
That trial was not a success. But this particular study volunteer has managed to consistently maintain a viral load below 100 copies/mL throughout the 15 years that have thus far passed since she interrupted ART during the course of the trial.
Researchers are not suggesting that this woman has been cured of HIV. In fact, lab testing of purified CD4 cell samples revealed that they were susceptible to HIV infection, and total HIV DNA remains detectable in CD4 cells (albeit at a 98% lower level from baseline).
That said, susceptibility tests revealed that the woman’s PBMCs appeared to be “highly resistant” to infection. In addition, a co-culture of her CD4 cells with both natural killer (NK) cells and CD8 cells yielded 93% inhibition of HIV replication—a rate much higher than that seen in co-cultures of CD4 cells with only NK cells (75% inhibition) or only CD8 cells (62% inhibition).
Further examination of these NK cells led the research team to discover that memory-like NK cells expressing NKG2C were circulating within the woman’s system at levels nearly twice as high as what’s normally seen in people experiencing typical HIV progression, and that NK cells expressing a CD57 marker appeared to have significant cytotoxicity when exposed to HIV-infected CD4 cells.
Similarly, unusually high levels of gamma-delta CD8 cells expressing NKG2C were discovered in the patient, which the researchers noted had been previously shown to have potent activity against HIV-infected CD4 cells.
That said, the researchers could not point to any traditional genetic factors that are typically associated with people who achieve natural control of HIV replication. They are similarly uncertain whether, or to what extent, the immune-modulating therapy the woman received as a part of the treatment interruption trial may have played a role: She was randomly assigned to the study arm that received cyclosporine A, GM-CSF, and peg-interferon alpha during an initial treatment interruption, then resumed ART along with low-dose interleukin-2 until the study ended.
Study information: Núria Climent et al, “Exceptional post-treatment control associated with strong NK and γδ cytotoxic T cells.”
Survey Suggests Particular Benefits of—and Obstacles to—LA-ART in Select Groups
Specific subsets of people living with HIV (PLWH)—such as people with a daily medication burden or those who have not disclosed their HIV status to people they live with—are likely to find a switch to long-acting injectable antiretroviral therapy (LA-ART) especially appealing, according to the results of a survey conducted in France.
A total of 581 French PLWH (79% of whom were men; median age, 52 years) completed an online questionnaire in 2021; researchers gained additional qualitative data via a 14-person focus group. Overall, 92% of survey respondents expressed at least some level of interest in LA-ART (48% expressed great interest), and 88% felt that LA-ART would improve their quality of life to some degree (with 48% perceiving it would do so by “a lot”).
Respondents expressed significantly more interest in LA-ART if they were living in a location where not everyone knew their HIV status relative to one where everyone knew (P = .003)—a situation reported by 23% of participants. Interest was also much higher among people taking at least one other daily treatment for a non-HIV chronic condition compared with those who were not (P = .006); half of survey respondents fell into this category.
Although participants expressed little fear regarding LA-ART injections, 34% suggested they would be unwilling to continue receiving them if side effects were to appear. In addition, concerns regarding logistical challenges were common, with 44% suggesting that the need to travel to a hospital to receive injections would be at least “somewhat” restrictive.
Study information: Cynthia Lacoux et al, “Interest of people living with HIV in injectable long-acting antiretroviral treatment: results from a flash AIDES survey.”
B/F/TAF Outperforms DTG + F/TDF as HBV Treatment in PLWH
Single-tablet bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, Biktarvy) is superior to a regimen of dolutegravir plus emtricitabine/tenofovir disoproxil fumarate (F/TDF, Truvada) as a treatment for hepatitis B (HBV) coinfection in ART-naive PLWH, according to 48-week results from a randomized trial.
The ALLIANCE study enrolled 243 people across 11 countries, primarily China, Malaysia, and Thailand. All participants were living with both HIV and chronic HBV infection and were naive to both ART and HBV treatment. The cohort was nearly all male (95%) and relatively young (median age 31 to 32, with no participant older than 39).
A substantial portion of study participants had relatively advanced HIV: Median CD4 count ranged from 236 to 245 cells/µL, and median HIV viral load was 4.7 log10 copies/mL. Similarly, HBV progression was notable among many participants: 52% had HBV DNA levels of 8 log10 or higher IU/mL, 78% were HBeAg positive, and 44% had ALT levels above the upper limit of normal.
Nonetheless, through 48 weeks of therapy (in a missing = failure analysis), 63% of participants in the B/F/TAF group had achieved HBV DNA levels below 29 IU/mL, compared with 43% of participants in the DTG plus F/TDF group (P = .0023). B/F/TAF recipients were significantly more likely to experience HBeAg seroconversion relative to DTG plus F/TDF recipients at 48 weeks; normalization of ALT levels and HBsAg and HBeAg loss were also trending in B/F/TAF’s favor at 48 weeks.
Unsurprisingly, HIV suppression rates were similarly high in the two regimens and overall rates of adverse events were similarly low across the study groups—although more individuals in the B/F/TAF group experienced ALT increases (20 vs. 13) and fasting LDL cholesterol increases (8 vs. 2).
Study information: Anchalee Avihingsanon et al, “Week 48 results of a Phase 3 randomized controlled trial of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs dolutegravir + emtricitabine/tenofovir Disoproxil Fumarate (DTG+F/TDF) as initial treatment in HIV/HBV-coinfected adults (ALLIANCE).”