BACKGROUND. We performed a Phase I clinical trial that infused CCR5 gene edited CD4 T cells to determine how these T cells can better enable HIV cure strategies. METHODS. The trial addressed the method of zinc finger nuclease (ZFN) ex vivo delivery, whether CCR5 Δ32 heterozygotes preferentially benefit, the effect of CCR5 gene edited CD4 T cells on the HIV-specific T cell response, and the ability of infused CCR5 gene edited T cells to delay viral rebound during analytical treatment interruption. We enrolled 14 people living with HIV whose viral load was well controlled by antiretroviral therapy (ART). We measured time to viral rebound after ART withdrawal, persistence of CCR5-edited CD4 T cells, and whether infusion of 10 billion CCR5-edited CD4 T cells augmented the HIV-specific immune response. RESULTS. Infusion of the CD4 T cells was well tolerated with no serious adverse events. Modest delay to the time of viral rebound was observed relative to historical controls; however, three of 14 individuals of which two were CCR5 Δ32 heterozygotes appeared to regain control of viremia before ultimately rebounding. Interestingly, only these individuals had substantial restoration of HIV-specific CD8 T cell responses. Immune escape to one of these re-invigorated responses was observed at viral recrudescence, illustrating a direct link between viral control and enhanced CD8 T cell responses. CONCLUSION. These findings demonstrate how CCR5 gene edited CD4 T cell infusion could aid HIV cure strategies by augmenting pre-existing HIV-specific immune responses.

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Frequent viral load testing is necessary during analytical treatment interruptions (ATIs) in HIV cure-directed clinical trials, though such may be burdensome and inconvenient to trial participants. We implemented a national, cross-sectional survey in the United States to examine the acceptability of a novel home-based peripheral blood collection device for HIV viral load testing. Between June and August 2021, we distributed an online survey to people with HIV (PWH) and community members, biomedical HIV cure researchers and HIV care providers. We performed descriptive analyses to summarize the results. We received 73 survey responses, with 51 from community members, 12 from biomedical HIV cure researchers and 10 from HIV care providers. Of those, 51 (70%) were cisgender men and 50 (68%) reported living with HIV. Most (>80% overall) indicated that the device would be helpful during ATI trials and they would feel comfortable using it themselves or recommending it to their patients/participants. Of the 50 PWH, 42 (84%) indicated they would use the device if they were participating in an ATI trial and 27 (54%) also expressed a willingness to use the device outside of HIV cure studies. Increasing sensitivity of viral load tests and pluri-potency of the device (CD4 count, chemistries) would augment acceptability. Survey findings provide evidence that viral load home testing would be an important adjunct to ongoing HIV cure-directed trials involving ATIs. Survey findings may help inform successful implementation and uptake of the device in the context of personalized HIV care.

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