Early press conference: cure, gay circumcision, PrEP choices, mpox, and COVID-19
1 August 2023. Related: Conference reports, mpox (monkeypox), HIV prevention and transmission, Cure-related research, COVID-19: HIV and COVID-19 coinfection, COVID-19, IAS 2023 Brisbane.
Simon Collins, HIV i-Base
IAS 2023 was one of the most important HIV conferences this year and an early press conference several days before the meeting included a handful of studies selected by the organisers.
Although these early reports in mainstream media might help the profile of the conference, they will usually be based on limited data from abstract summaries and a short informal talk from the lead author.
This is not a good way to present the results from years or research and it undermines the importance of full access to the study details before these have been presented in a peer-reviewed context.
With this caveat, please read these early reports cautiously – including from i-Base.
Our later coverage however will benefit from access to the full data.
A potential HIV cure from a stem cell donor susceptible to HIV
The press conference led with a new potential case of HIV cure presented by Asier Sáez-Cirión from the Pasteur Institute, Paris and Alexandra Calmy from the Institute of Hospitals, Sion, Switzerland, on behalf of the ICISTEM study group.
As with the five previous cases – this will be the sixth – this involved undergoing a complicated and risky allogeneic hematopoietic stem cell transplant (aHSCT) that was needed to treat refractory cancer. This case is notable however for not using a donor with the CCR5 delta-32 deletion which produces a genetic barrier against the most common strain of HIV.
Although the exact mechanism for earlier cure cases is not fully understood, having a donor with the CCR5 delta-32 deletion has up until now been thought to be essential.
In 2018, this person received chemotherapy to treat a biphenotypic sarcoma followed by aHSCT from an unrelated HLA-matched (9/10) wild-type CCR5 donor.
He stopped ART in November 2019 and has now been off-ART for 20 months without detection of rebound viremia or replication-competent HIV. HIV DNA has not been detected in blood or tissue samples, and testing for HIV-specific T-cell responses are also negative. Nevertheless, this is still a relatively short time and further follow-up is needed.
The individual concerned is a man in his fifties who was diagnosed HIV positive in 1990 and he has been on continuous effective ART since 2005. He has chosen to remain anonymous at the moment and is being referred to as the Geneva patient.
He is also case number 34 in the Icistem database. [2]
Further information about the treatment procedures and subsequent follow-up will become available after the case is presented in the main conference.
Early cases of viral suppression off-ART in five infants
Another cure-related study in the press conference included early cases of viral control presented by Gabriela Cromhout from the University of KwaZulu-Natal. The five infants, all male, were part of a longitudinal study from 2015 to 2023 involving 281 mother-child pairs monitored from delivery following in utero HIV transmission.
Intermittent adherence identified by ART drug levels showed periods for viral control off-ART from 3 to 10 months. One child never used ART and has remained undetectable for 19 months. Most of the others are now back on ART. [3]
The results included differences in viral sensitivity to type I interferon (IFN-I) by sex and viral replicative capacity, which was significantly lower in the five cases reported.
As with other studies in the report, further details will be reported during the actual conference presentation.
Targeting the viral reservoir with anticancer drug delays viral rebound in mice
Also cautiously, the press conference reported that the anticancer drug venetoclax has activity in human cells ex vivo and target the viral reservoir in a study in humanised mice.
The impact of daily dosing for six weeks was to significantly delay the time to viral rebound in the treated mice especially when used with a second protein inhibitor S63845. [4]
The investigators, including IAS president Professor Sharon Lewin who chaired the press conference, noted that extensive experience of venetoclax as an approved drug warrants further research in human studies.
Circumcising gay men as HIV prevention
Both observational and interventional studies have reported that circumcision approximately halves the chance that heterosexual men become HIV positive. [5]
The context is that men are having insertive sex with the likely mechanism being due to the inner foreskin being a mucous membrane with a high concentration of HIV target CD4 cells. [6]
As an HIV prevention strategy, the benefits have been seen in settings where HIV prevalence is high. It is also essential that the intervention is voluntary medical circumcision (VMMC) in adult men rather than just circumcision. Although VMMC is still used in some countries as an HIV prevention strategy it is notable that these studies pre-dated PrEP.
Up until now, circumcision has not been reported as effective for gay and bisexual men, largely because of the higher remaining risk from receptive sex and that few men are exclusively active. A positive benefit was reported in an Indian study of MSM at least ten years ago, which was also before PrEP.
Yanxiao Gao from Sun Vat-sen University, Shenzhen, presented results of a very small randomised study of immediate vs delayed circumcision in 247 gay men enrolled in eight Chinese cities who mainly had insertive sex. [7]
After approximately 116 person-years of follow-up in each arm, there were zero vs five HIV seroconversion in the immediate vs deferred groups respectively. This was reported as an HIV incidence rate (IR), per 100 person-years of 0.00 (95% Cl: 0.00 to 3.18) vs 4.27 (95% CI: 1.38 to 9.97) arms.
Adverse events related to VMMC were mild and resolved quickly. The abstract notes that final results are expected by July 2023 and so are likely to be presented at the actual conference.
The short presentation of this study noted that the intervention was designed in China due to the very limited access to PrEP. Also, that although results would need to be confirmed in larger studies, these are unlikely to be run in countries where PrEP is available.
Choice of injectable vs oral PrEP in extension to HPTN-084 study
The HPTN 084 study showed that injectable cabotegravir (CAB) was superior to oral PrEP at preventing HIV infections on cisgender African women due to more difficult adherence associated with daily oral pills.
All participants then had the option to choose PrEP formulations in the open label extension (OLE) to this phase 3 study and results of this choice were presented in the press conference before IAS 2023. Results were presented by lead Delany-Moretlwe from the University of the Witwatersrand, South Africa. [8]
The abstract reports that 2472/3028 women from HPTN-084 enrolled in the OLE study. Of these, 1931/2472 (78%) chose injections and 536 (22%) chose oral PrEP.
Previous experience affected the choice to change formulations. Of those originally using oral PrEP, approximately 67% chose injections and 33% continued on oral treatment. Of those originally using injections, approximately 89% continued injections and 11% switched to oral treatment.
Reasons for choosing injections included preferred injections (77%), being more convenient (11%) and effectiveness (8%).
Choosing oral PrEP was linked to preferring pills (81%), fear of injections (5%), wanted to become pregnant (1%) or efficient benefit of clinic visits (1%).
Most participants (66%) reported their choice was their own, discussions with study staff (20%) or family and friends (11%) were also influential.
Although the majority of participants chose injectable PrEP, a significant majority continued or switched to oral PrEP, showing the importance of choice.
HIV and mpox: WHO review
Ana Hoxha from WHO presented a review of date on mpox collected from January to December 2022 as part of the WHO international case-based surveillance programme. This reported that immunosuppression rather than HIV increases the risk associated with mpox. [9]
In some countries up to 50% of cases were in men living with HIV and this study reported on whether HIV status was related to serious mpox outcomes including hospitalisation, admission to ICU or death.
Of the 80,843 cases reported, HIV status was available for 44%. Of these, approximately half (16,788) were living with HIV.
Although the data was limited, immunosuppression was reported in 5,023 of the cases in people living with HIV, 735 were hospitalised, 20 admitted to ICU, and 23 died. Immunosuppression increased the risk of hospitalisation in cases that were HIV positive (OR: 2.00 (95% Cl: 1.64 to 2.43, p<0.001) and HIV negative (OR: 3.56 (95%CI: 1.80 to 7.01) p<0.001).
Due to the small sample size, no risk factors for ICU admission and death were found.
This study rightly emphasised the need for increased HIV testing in people at higher risk for mpox.
HIV and COVID-19
While the mpox epidemic dramatically declined in most countries by the end of 2022, COVID-19 is still ongoing, albeit with reduced numbers.
A second study from the WHO surveillance team reported on the impact of COVID-19 on the risk of mortality in people living with HIV during the pre-Delta, Delta and Omicron variant waves.
Silvia Bertagnoli from WHO summarised this study at the press conference referring to data from the abstract. [10]
Compared to people without HIV, people living with HIV had a 54% (aHR 1.54, 95%CI: 1.42 to 1.68), 56% (aHR 1.56, 95%CI: 1.4 to -1.74) and 142% (aHR 2.42, 95%CI: 2.11 to 2.78) increased risk of mortality in adjusted analyses, during the pre-Delta, Delta and Omicron variant waves, respectively.
Having a low CD4 count less than 200 cells/mm3 was consistently linked to poorer outcomes and vaccination was consistently linked with lowering this risk.
References
Unless stated otherwise, all references are to the programme and abstracts of the 12th IAS conference 23 to 26 July 2023, Brisbane, Australia. Abstract URLs are initially restricted to delegates and might also change later.
- Sáez-Cirión A et al. Absence of viral rebound for 20 months without antiretrovirals after allogeneic hematopoietic stem cell transplantation with wild-typeCCR5 donor cells to treat a biphenotypic sarcoma. IAS 2023, Brisbane. Oral abstract OALBA0504.
https://programme.ias2023.org/Abstract/Abstract/?abstractid=5819 - International Collaboration to guide and investigate the potential for HIV cure by Stem Cell Transplantation (Icistem).
https://www.icistem.org - Cromhout G et al. Sustained aviraemia in the absence of anti-retroviral therapy in male children following in utero vertical HIV transmission. IAS 2023, Brisbane. Oral abstract OALBX0104.
https://programme.ias2023.org/Abstract/Abstract/?abstractid=5727 - Arandjelovic P et al. Venetoclax, alone and in combination with the BH3-mimetic S63845, depletes HIV-1 latently infected cells and delays rebound in humanized mice. IAS 2023, Brisbane. Oral abstract OALBA0503.
https://programme.ias2023.org/Abstract/Abstract/?abstractid=5735 - Gray RH et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet 2007; 369:657-666.
https://pubmed.ncbi.nlm.nih.gov/17321311/ - Collins S. Male circumcision: new data supporting protective mechanism. HTB (February 2010).
https://i-base.info/htb/7782 - Gai Y et al. Voluntary medical male circumcision and incident HIV acquisition among men who have sex with men: a randomized controlled trial. IAS 2023, Brisbane. Oral abstract MOPEC16.
https://programme.ias2023.org/Abstract/Abstract/?abstractid=1002 - Delany-Moretlwe S et al. Initial PrEP product choice: results from the HPTN 084 open-label extension. IAS 2023, Brisbane. Oral abstract OALBX0203.
https://programme.ias2023.org/Abstract/Abstract/?abstractid=5998 - Hoxha A et al. HIV among mpox cases: clinical characteristics and outcomes in the WHO global surveillance 2022. IAS 2023, Brisbane. Oral abstract OAB0302.
https://programme.ias2023.org/Abstract/Abstract/?abstractid=3953 - Bertagnolio S et al. High in-hospital mortality in SARS-CoV-2 infected patients living with HIV during pre-Delta, Delta and Omicron variant waves: finding from the WHO Global Clinical Platform for COVID-19. IAS 2023, Brisbane. Oral abstract OALBC0604.
https://programme.ias2023.org/Abstract/Abstract/?abstractid=5988
This report was first posted on 20 July 2023.