IMPAACT Shares Study Results in CROI 2022 Oral Presentations

HIV-1 Remission with CCR5∆32∆32 Haplo-Cord Transplant in a U.S. Woman: IMPAACT P1107 

Study: IMPAACT P1107 

IMPAACT P1107 is an observational study of persons living with HIV in the U.S. who undergo transplantation with CCR5Δ32 cord blood stem cells for treatment of cancer or other illness. The study began in 2015 and has been conducted by the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network, in collaboration with the Center for International Blood and Marrow Transplant Research (CIBMTR), StemCyte, and the AIDS Clinical Trials Group (ACTG). 

The CCR5Δ32 genetic mutation results in T cells that are missing CCR5 co-receptors. HIV uses these co-receptors to infect T cells. T cells are part of the immune system. Scientists theorize that chemotherapy given to people with cancer or other illness, followed by a transplant with stem cells that carry the CCR5Δ32 mutation, can change the immune system to make it resistant to HIV.  

Study Results 

At CROI 2022, the IMPAACT P1107 Protocol Team presented the first known case of a woman with HIV remission following a stem cell transplant for treatment of acute myelogenous leukemia (AML). The transplant consisted of cord blood stem cells with the CCR5Δ32 genetic mutation and haploidentical peripheral blood stem cells from a relative. Since having the stem cell transplant, the participant has been in remission for AML.  

The participant’s HIV infection was well-controlled on antiretroviral therapy (ART) prior to the stem cell transplant and through 37 months post-transplant, at which time she stopped ART. With the exception of transient detection of trace levels of HIV-1 DNA in blood cells 14 weeks after stopping ART, no HIV has been detected for 14 months. Based on these results, the participant has been deemed in HIV remission.  

HIV remission resulting from a stem cell transplant had been previously observed in two cases. The first, known as the “Berlin patient” (a Caucasian male), experienced HIV remission for 12 years and was deemed cured of HIV. He died of leukemia in September 2020. The “London patient” (a Latino male) has been in HIV remission for more than 30 months. This third case, reported from IMPAACT P1107 in a woman of mixed race, suggests that CCR5Δ32 cord stem cell transplantation should be considered to achieve HIV remission for people living with HIV who require such a transplant for another illness. 

Two Year Virologic Outcomes of Very Early ART for Infants in the IMPAACT P1115 Study 

Study: IMPAACT P1115 

IMPAACT P1115 is a Phase I/II, proof-of-concept study evaluating responses to very early intensive antiretroviral therapy (ART) initiated within 48 hours of birth. The study began enrolling in January 2015. Participants have been enrolled at 30 clinical research sites in 11 countries across Africa, Asia, and the Americas. 

Study Results 

Findings presented at CROI 2022 were based on data collected among 54 infants with in utero HIV infection through two years of age. These infants were enrolled in two cohorts and received an ART regimen initially comprised of nevirapine and two non-nucleoside reverse transcriptase inhibitors; lopinavir/ritonavir was added to the regimen when age appropriate, and nevirapine was stopped 12 weeks after confirmed virologic suppression.   

The protocol team summarized that a substantial proportion of infants who maintained virologic suppression through two years of age achieved low reservoir size, potentially enabling ART-free remission. Further detailed findings can be found in the team’s oral and poster presentations, available here and here.

Growth of Breastfed Infants Exposed in Utero to Maternal DTG vs EFV and TDF vs TAF 

Study: IMPAACT 2010 

IMPAACT 2010/VESTED was a Phase III, three-arm, randomized, open-label study of pregnant women with HIV initiating either a dolutegravir (DTG)-containing antiretroviral regimen or an efavirenz (EFV)-containing antiretroviral therapy regimen at 14-28 weeks' gestation. Women and their infants were followed for one year following delivery or pregnancy outcome. Primary study results were presented and published previously. The results of several secondary and exploratory analyses were presented at CROI 2022, as described below.

Study Results: 

Lynda Stranix-Chibanda reported on infant growth in the first year of life, following in utero exposure to DTG+FTC/TAF, DTG+FTC/TDF, or EFV/FTC/TDF. Most infants were breastfed. Infants born to mothers randomized to the EFV arm were significantly smaller than infants born to mothers randomized to either of the DTG arms. Rates of severe stunting were high across all arms, but highest in the EFV arm (1 in 5 compared to 1 in 7 for the DTG arms). 

The following key results were also provided in poster presentations: 

• A desirability of outcome ranking analysis identified DTG+FTC/TAF as providing the best and clearest risk-benefit trade-off for mothers and infants. 
• Among women with virologic failure, resistance at baseline was common. Women in the DTG arms had significantly lower rates of virologic failure and ARV drug resistance compared to women in the EFV arm.  
• There were no significant differences in HbA1c (an early marker of diabetes) and random glucose levels among women by randomized arm. 
• Among 19 women who became pregnant again while on study, adverse pregnancy outcomes were very common. At least one adverse pregnancy outcome occurred in 58% of these pregnancies, and adverse outcomes were more frequent for women on EFV versus DTG at conception.