IAS 2025 Day One Conference Report

Dear Consortium Members and Supporters,

Tuesday, July 15th, 2025

Tuesday, July 15th marked the first full day of the IAS 2025 conference, with numerous significant developments in HIV research and treatment to report.

Opening News: PEPFAR Funding Secured

In encouraging news, the US Senate successfully preserved the Global AIDS program PEPFAR from congressional funding cuts. This development comes as welcome relief following dire predictions of potential deaths if funding reductions had proceeded, as detailed in a recent Lancet article, June 30th 2025,  reviewed yesterday.

Tragically, the first pediatric death in Mozambique was reported on June 25th and discussed at today’s meeting. The child had maintained good health on HIV treatment for over six years but lost access to medications in January when USAID cuts occurred. Without treatment, the child died.

Key Conference Highlights

1. Elite Controllers

Dr. Xu Yu from Harvard Medical School presented groundbreaking research on elite controllers as a pathway to HIV cure development. Viral reservoirs remain the primary barrier to curing HIV, with elite controllers classified into two types:

  • Type I: Complete absence of proviral DNA in elite controllers
  • Type II: Minimal levels of proviral DNA

Viral reservoirs present major obstacles to cure due to their characteristics: extremely small numbers, establishment during acute HIV infection before the virus becomes detectable, resistance to most HIV medications, decades-long persistence, and responsibility for viral rebound requiring lifelong therapy.

Dr. Yu provided updates on two remarkable patients. The San Francisco patient has eliminated HIV without antiretroviral treatment and may have achieved natural cure for 30 years, including the past six years following aggressive chemotherapy for lung cancer. Despite severe immunosuppression from chemotherapy, this patient maintained an undetectable viral load.

The Esperanza patient has been followed for many years without detectable virus. Researchers are studying these elite controllers to develop vaccination strategies that could educate immune systems to control HIV without antiretroviral therapy.

2. Long-Acting Agents: Injectable, Oral, Patch, and Implant Formulations

Dr. Cissy Kityo Mutuluuza from Uganda discussed advances in long-acting agents. While long-acting injectable agents were added to WHO and DHHS guidelines in 2024, Johnson & Johnson will discontinue rilpivirine manufacturing for African patients, leaving no regimen without it. Generic alternatives are expected soon, though this won’t affect US availability.

Key developments include:

  • Cabotegravir/Rilpivirine (Cabenuva©): Extended dosing intervals from every two months to every four months
  • Lenacapavir (Sunlenca©): Oral formulation studies for weekly two-drug regimens, combined with investigational drugs islatravir (ISL) and ulonivirine (ULO)
  • Prevention applications: Lenacapavir approved for six-monthly injection as prevention (Yeztugo©)
  • Future directions: Implants and patches under study for six-month dosing intervals, showing up to 100% efficacy

3. Community Involvement and Stakeholder Engagement

Magda Lopes Queta, Executive Director of ENDA Santé in Senegal, emphasized transforming people living with HIV from beneficiaries to stakeholders and leaders. She highlighted successful innovative sexual and reproductive health programs in challenging social and political contexts, prioritizing local knowledge and community leadership.

4. Monoclonal Antibodies (bNAbs)

Initial reports demonstrate that two subcutaneous broadly neutralizing antibodies (bNAbs) can be used together without mutual neutralization and combined with oral agents. The combination of long acting lenacapavir (LEN) with bNAbs teropavimab (TAB) and zinlirvimab (ZAB) show promise.

While antibodies alone haven’t achieved HIV cure, combination with treatments like LEN offers hope for successful treatment and potential cure. Eron et al. reported promising results with T-cell responses in a 26-week treatment study with 32 participants randomized to different ZAB doses. High-dose treatment achieved suppression in 15/16 participants at week 26, while low-dose treatment suppressed 11/14 participants.

5. Non-Daily PrEP and PEP

Current prevention options include oral PrEP, two-month long-acting injectable cabotegravir, six-monthly long-acting injectable lenacapavir, and dapivirine vaginal rings.

Doxy-PEP (post-exposure prophylaxis): 200mg single dose within 24-72 hours after sexual exposure, with optimal effectiveness within 24 hours. Weekly dosing regimens are under investigation.

Doxy-PrEP (pre-exposure prophylaxis): 100mg daily for individuals engaging in high-risk sexual activity more than 50% of the month. Daily dosing may reduce antibiotic resistance risk (Anne Luekemeyer). Jean Michel Molina’s study of weekly Doxy-PrEP showed reduced chlamydia and syphilis but not gonorrhea, like prior studies with PEP 200mg single dose after sex.

6. New WHO Guidelines

  • Pediatric guidelines: Including abacavir use for neonatal PEP.
  • Lenacapavir recommendation: Twice-yearly pre-exposure prophylaxis, representing a game-changer for resource-limited countries
  • Community involvement: Emphasizing meaningful engagement of people living with HIV

7. Intermittent ART Dosing

In a surprising report that shocked the audience, a meta-analysis of eight studies with 1,346 participants found no significant difference between daily versus 3-5 days weekly standard ART over 24 weeks. This strategy emerged following PEPFAR and USAID cuts in January 2025.Fortunately, on July 15th, 2025, the US House blocked the bill that would have cut PEPFAR and USAID, providing relief for global HIV treatment.

Patient satisfaction favored intermittent dosing: 59% were satisfied with intermittent ART versus 7% with continuous treatment. However, concerns exist about resistance formation, particularly with NNRTIs due to their long half-lives potentially creating functional monotherapy.

Current supply chain disruptions affect 46% of countries with individuals experiencing ART shortages. While results appear promising, longer observation periods beyond 24 weeks are needed to ensure sustained effectiveness.

8. ART-Associated Weight Gain

Excessive weight gain has been associated with integrase inhibitors (INSTI) and tenofovir alafenamide (TAF). ACTG A5391 evaluated switching to doravirine (Pifeltro©) with or without tenofovir disoproxil fumarate (TDF) in people with HIV and obesity on INSTI+TAF regimens.

Unfortunately, switching from INSTI+TAF/FTC to doravirine/FTC with either TAF or TDF did not result in substantial weight change at one year, including among women and Black patients.

A large retrospective study of 10,413 patients from 12 US geographic areas identified weight gain associations with baseline BMI, younger age (18-29), normal baseline BMI, CD4<200, female sex, and Black race. However, weight gain patterns did not differ significantly from the general US population over three years of observation, with no association to specific HIV medications.

9. Anal Dysplasia Treatment Advances

Anal cancer screening with anal Pap smears has demonstrated strong prevention of progression to invasive anal cancer in patients with abnormal results, including LSIL (low-grade dysplasia) or HSIL (high-grade anal dysplasia).

The TECAIN study compares two treatment methods for anal intraepithelial neoplasia (AIN) in people living with HIV: topical trichloroacetic acid (TCA) and local electrocautery ablation (ECA). TCA showed good tolerability and required less local anesthesia but needed more treatment sessions. Additional patients are needed to determine if this less painful procedure provides equivalent prevention to ECT or IRC (infrared coagulation used in the US).

Conclusion

Day 1 of IAS 2025 presented both challenges and significant advances in HIV treatment and prevention, from policy victories preserving global funding to innovative treatment approaches. While funding cuts have had tragic consequences, the restoration of PEPFAR funding provides hope. Scientific advances in long-acting therapies, community engagement, and novel treatment approaches offer promising paths forward in the fight against HIV.

Conference coverage will continue tomorrow (7/16/25) for Day Two.