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AIDS 2022 News Release: Doxycycline Reduced STIs; Functional cure case; Stem Cell Transplant Cure Care; TAF vs TDF for HBV in ART regimen.
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AIDS 2022 spotlights a game-changing tool to prevent sexually transmitted infections and key advances in HIV cure research
Studies highlighted at the 24th International AIDS Conference provide insights on new and existing strategies to help end the HIV epidemic.
27 July 2022 (Montreal, Canada) - New studies presented at AIDS 2022, the 24th International AIDS Conference, hosted by IAS - the International AIDS Society - demonstrate promising advances in the global HIV response.
Speaking at a virtual press conference, authors shared:.
• Successful results from a trial of the antibiotic doxycycline to prevent sexually transmitted infections (STIs)
• Reports of two adults in long-term remission off antiretroviral therapy (ART)
• A new method using microfluidics to define a biomarker of the HIV reservoir
• News of Botswana surpassing global 95-95-95 targets to nearly eradicate the epidemic in the country
• Promising results of a triple-therapy regimen for people living with both HIV and hepatitis B
"A cure remains the Holy Grail of HIV research," Sharon Lewin, IAS President-Elect and Director of The Peter Doherty Institute for Infection and Immunity, said. "We have seen a handful of individual cure cases before, and the two presented today provide continued hope for people living with HIV and inspiration for the scientific community. What's more, we are now seeing an advance in the great challenge of finding a biomarker for the HIV reservoir - a truly exciting development."
Today's scientific press conference highlighted six studies selected from thousands of abstracts being presented over the next week in Montreal and virtually.
Doxycycline significantly reduces risk of STIs after condomless sex by 65%
The DoxyPEP study found that taking 200mg of doxycycline within 72 hours of condomless sex significantly reduces the risk of gonorrhoea, chlamydia and syphilis among men who have sex with men and trans women. Among those randomized to take doxycycline, 65% fewer were diagnosed with an STI each quarter than those not taking doxycycline.
Participants in the study were male sex at birth, living with HIV or taking HIV pre-exposure prophylaxis (PrEP) and had a history of an STI and condomless sex with a male partner within in the past year. They were randomized 2:1 to take open-label doxycycline after condomless sex versus continued standard of care without doxycycline.
Among the 327 participants taking PrEP, there was a 66% reduction in new STIs per quarter (doxycycline 10.7% versus control 31.9%, p<0.001). Of the 174 participants living with HIV, there was a 62% reduction per quarter with doxycycline (11.8% vs 30.5%, p<0.0001).
Participants reported taking doxycycline 87% of the time after condomless sex; 54% reported taking fewer than 10 doses per month, 30% took 10-20 doses per month, and 16% took more than 20 doses per month. No serious or >Grade 2 adverse events were attributed to doxycycline.
Analyses of the impact of intermittent doxycycline on antimicrobial resistance and the gut microbiome are ongoing.
The DoxyPEP study was stopped early in May 2022 when a planned interim analysis showed that those randomized to take doxycycline had substantially fewer STIs.
Co-principal investigator Annie Luetkemeyer, Professor of Medicine at Zuckerberg San Francisco General Hospital at University of California, San Francisco, noted that doxycycline taken after sex is a promising prevention strategy for populations disproportionately impacted by high rates of STIs.
"DoxyPEP represents an important advance in reducing STIs within two vulnerable populations - men who have sex with men and transgender women," Lewin said. "I look forward to learning more about the implementation of this prevention measure and any long-term effects of using antibiotics for STI prevention."
The trial was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, through grant R01AI143439. It was conducted at the HIV clinic at Zuckerberg San Francisco General Hospital and the San Francisco City Clinic, both part of the San Francisco Department of Public Health, and the Madison Clinic and the Sexual Health Clinic at Harborview Medical Center, both at the University of Washington.
Abstract and session: Doxycycline post-exposure prophylaxis for STI prevention among MSM and transgender women on HIV PrEP or living with HIV: high efficacy to reduce incident STI's in a randomized trial, Co-Chairs Choice (13231, Track B)
Stem-cell transplant recipient becomes fourth known adult case of HIV cure
A 66-year-old Caucasian man who received a stem cell transplant is the fourth known person to go into HIV remission. Data presented today by Jana Dickter of City of Hope describes the case of the man, diagnosed with HIV in 1988, who received chemotherapy and an allogeneic hematopoietic stem cell transplant (aHCT) after developing acute myelogenous leukaemia in 2018. Previously, he had an undetectable HIV-1 viral load on ART for many years.
The transplant recipient continued ART for 25 months after aHCT and his ART levels remained undetectable 12 months post-analytic treatment interruption. As of 14 months after stopping treatment and 39 months post-transplantation, there is no evidence of HIV RNA rebound and no detectable HIV DNA.
Declining HIV-1 specific humoral and no detectable HIV-specific cellular immune response was observed. The man's CD8-depleted peripheral blood mononuclear cells remained uninfected after an ex vivo challenge with HIV R5 strains. Immunological studies 37 months after the aHCT and 12 months post-analytic treatment interruption showed a robust response to cytomegalovirus stimulation and no response to HIV CD4 and CD8 T cells.
This case may open up the opportunity for older people living with HIV and blood cancer to receive a stem cell transplant and go into remission for both diseases.
For more information, visit.
Abstract and session: 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)
Late breaker Track B (12508, Track B)
Latest functional cure case sheds new light on post-treatment controllers
A 59-year-old woman with sexually acquired HIV and enrolled in the "Immune-mediated PHI trial" has maintained an undetectable viral load for more than 15 years without ART. Núria Climent, researcher at Hospital Clínic-IDIBAPS/University of Barcelona, presented an analysis of her case.
After receiving antiretroviral and immunomodulatory treatment, including eight weeks of cyclosporine, during primary HIV infection, the woman has maintained undetectable viral load in plasma for more than 15 years without ART. A pronounced and progressive fall of the viral reservoir was observed in total HIV-DNA (from 4,573.50 to 95.33 copies/106 CD4+ T-cells) and integrated proviral DNA (from 85.37 to 5.25 copies/106 CD4+ T-cells).
The authors noted that study results showed that replication-competent HIV-1 could be isolated by qVOA. They also reported that NKG2C+-memory-like NK-cells and Yd+CD8+ T-cells could contribute to the control of viral replication and functional cure observed.
For more information, visit.
Abstract and session: Exceptional post-treatment control associated with strong NK and γɗ cytotoxic T-cells, Responding to the virus: Advance in HIV immunology (5149, Track A)
Advances in the search for a biomarker for the HIV reservoir
Eli Boritz of the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID) presented results from a study using a custom microfluidics process that was developed for gene expression profiling of rare HIV-infected cells, including those cells harbouring latent HIV DNA genomes.
The research team, which included scientists from VRC/NIAID, UCSF and Brigham and Women's Hospital, used a microfluidic droplet-sorting technology termed FIND-Seq (Focused Interrogation of cells by Nucleic acid Detection and Sequencing) to sequence the transcriptomes of HIV DNA+ memory CD4 T cells from the blood of six people living with HIV who received long-term ART initiated during chronic infection. Host cell transcriptomic profiles of HIV DNA+ and uninfected memory CD4 T cells were compared by differential gene expression, co-expression network analyses and gene ontology.
HIV DNA+ memory CD4 T cells showed inhibition of six transcriptomic pathways, including death receptor signalling, necroptosis signalling and Ga12/13 signalling. Gene co-expression network analysis revealed two small gene clusters associated with HIV DNA+ cells. Gene ontology revealed significant enrichment of these clusters for factors related to gene regulation, RNA processing and the regulation of cell activation, proliferation and survival. Individual genes in these clusters included HIV transcriptional activators that were lower in HIV DNA+ cells and HIV silencing factors affecting both transcriptional and post-transcriptional steps in HIV gene expression that were higher in HIV DNA+ cells.
The results presented by Boritz describe HIV-infected memory CD4 T cells as a distinctive cell population with gene expression patterns that can promote HIV persistence through HIV latency, cell survival and cell proliferation.
Abstract and session: Transcriptional programs of HIV silencing and cell survival in HIV-infected memory CD4 T cells under antiretroviral therapy, Co-Chairs choice (12900, Track A)
First-ever comparison of TAF versus TDF in people living with HIV and hepatitis B virus (HBV)
A Phase 3, multi-country ALLIANCE study comparing bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and dolutegravir + tenofovir disoproxil fumarate (DTG+F/TDF) for the treatment of adults with both HIV-1 and HBV found that B/F/TAF resulted in superior HBV DNA suppression and significantly more HBeAg seroconversion despite both B/F/TAF and DTG+F/TDF having high HIV suppression at one year.
Study participants were randomized 1:1 to initiate blinded treatment with B/F/TAF or DTG+F/TDF; primary endpoints were proportion of participants with HIV-1 RNA <50 copies/mL and plasma HBV DNA <29 IU/mL at 48 weeks. Antiretroviral regimens containing tenofovir are currently recommended for most people living with HIV and HBV, but this is the first randomized study evaluating TAF versus TDF in treatment-naive individuals with co-infections.
Those treated with B/F/TAF had numerically higher HBsAg and HBeAg loss, HBeAg seroconversion and ALT normalization. However, both ART regimens achieved HIV-1 RNA <50 copies/mL (95% versus 91%) with mean CD4 gains of 200 and 175 cells/mL, respectively. The most frequent adverse events were upper respiratory tract infection, COVID-19, pyrexia, ALT increase and nasopharyngitis. ALT flares occurred in 11 participants but resolved.
Anchalee Avihingsanon of HIV-NAT, Thai Red Cross AIDS Research Centre, noted that the clinical course of HBV in individuals with HIV is marked by accelerated disease progression, and this study represents an important advancement in successfully treating the many people living with HIV/HBV.
"The ALLIANCE study findings are very exciting given the superior activity of B/F/TAF on hepatitis B markers," Lewin noted. "These findings not only have implications for people living with both HIV and hepatitis B, but also for the many people living with HBV alone."
Abstract and session: 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), Co-Chairs choice (12565, Track B)
Botswana achieves 95-95-95 targets
Botswana has become one of the very few countries to surpass the Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 targets, a population-based survey confirmed. The survey found that 95.1% of people living with HIV in Botswana were aware of their status, nearly all (98%) of those aware of their status were on antiretroviral therapy, and 97.9% of those on ART achieved viral suppression.
Since offering free HIV treatment to all citizens, Botswana has expanded treatment coverage and implemented test-and-treat programmes that provide immediate treatment to people who test positive for HIV.
The rigorous, population-based survey involved visiting thousands of households to offer HIV and viral load testing.
Presenter Madisa Mine of the Botswana Ministry of Health and Wellness noted that the country is well-positioned to end its HIV epidemic by 2030 despite the fact that approximately one in five adults in Botswana are living with HIV.
"The results from this large-scale survey of Botswana's progress are truly breath-taking," Lewin said. "This important milestone demonstrates exactly what evidence-based policies can deliver."
Abstract and session: Botswana achieved the Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 targets: Results from the Fifth Botswana HIV/AIDS Impact Survey (BAIS V), 2021, Poster presentation (12921, Track C)
New UNAIDS report launches today
Also timed with the conference, UNAIDS will launch a new report entitled In Danger: The UNAIDS Global AIDS Update 2022. Noting the impact of recent crises on the global AIDS response, the report will outline the latest changes in access to HIV resources and new data on the number of global acquisitions.
The report will be made available online later today at www.unaids.org
Note: Press summaries are based on abstracts; final data presented at the conference may change.
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