Intact Human Immunodeficiency Virus (HIV) Reservoir Estimated by the Intact Proviral DNA Assay Correlates With Levels of Total and Integrated DNA in the Blood During Suppressive Antiretroviral Therapy.

Accurate characterization of the human immunodeficiency virus (HIV) reservoir is imperative to develop an effective cure. HIV was measured in antiretroviral therapy-suppressed individuals using the intact proviral DNA assay (IPDA), along with assays for total or integrated HIV DNA, and inducible HIV RNA or p24. Intact provirus correlated with total and integrated HIV.

Pegylated Interferon alfa-2a monotherapy results in suppression of HIV type 1 replication and decreased cell-associated HIV DNA integration.

BACKGROUND: Antiretroviral therapy (ART)-mediated immune reconstitution fails to restore the capacity of the immune system to spontaneously control human immunodeficiency virus (HIV) replication. METHODS: A total of 23 HIV type 1 (HIV-1)-infected, virologically suppressed subjects receiving ART (CD4(+) T-cell count, >450 cells/µL) were randomly assigned to have 180 µg/week (for arm A) or 90 µg/week (for arm B) of pegylated (Peg) interferon alfa-2a added to their current ART regimen. After 5 weeks, ART was interrupted, and Peg-interferon alfa-2a was continued for up to 12 weeks (the primary end point), with an option to continue to 24 weeks. End points included virologic failure (viral load, ≥ 400 copies/mL) and adverse events. Residual viral load and HIV-1 DNA integration were also assessed. RESULTS: At week 12 of Peg-interferon alfa-2a monotherapy, viral suppression was observed in 9 of 20 subjects (45%), a significantly greater proportion than expected (arm A, P = .0088; arm B, P = .0010; combined arms, P < .0001). Over 24 weeks, both arms had lower proportions of subjects who had viral load, compared with the proportion of subjects in a historical control group (arm A, P = .0046; arm B, P = .0011). Subjects who had a sustained viral load of <400 copies/mL had decreased levels of integrated HIV DNA (P = .0313) but increased residual viral loads (P = .0078), compared with subjects who experienced end-point failure. CONCLUSIONS: Peg-interferon alfa-2a immunotherapy resulted in control of HIV replication and decreased HIV-1 integration, supporting a role for immunomediated approaches in HIV suppression and/or eradication. CLINICAL TRIALS REGISTRATION: NCT00594880.

Preliminary Acceptability of a Home-Based Peripheral Blood Collection Device for Viral Load Testing in the Context of Analytical Treatment Interruptions in HIV Cure Trials: Results from a Nationwide Survey in the United States.

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.

"We are looking at the future right now": community acceptability of a home-based viral load test device in the context of HIV cure-related research with analytical treatment interruptions in the United States.

BACKGROUND: People with HIV (PWH) and community members have advocated for the development of a home-based viral load test device that could make analytical treatment interruptions (ATIs) less burdensome. OBJECTIVE: We assessed community acceptability of a novel home-based viral load test device. METHODS: In 2021, we conducted 15 interviews and 3 virtual focus groups with PWH involved in HIV cure research. We used conventional thematic analysis to analyze the data. RESULTS: PWH viewed the home-based viral load test device as a critical adjunct in ongoing HIV cure trials with ATIs. The ability to test for viral load at home on demand would alleviate anxiety around being off ART. Participants drew parallels with glucometers used for diabetes. A preference was expressed for the home-based test to clearly indicate whether one was detectable or undetectable for HIV to mitigate risk of HIV transmission to partners. Perceived advantages of the device included convenience, sense of control, and no puncturing of veins. Perceived concerns were possible physical marks, user errors and navigating the logistics of mailing samples to a laboratory and receiving test results. Participants expressed mixed effects on stigma, such as helping normalize HIV, but increased potential for inadvertent disclosure of HIV status or ATI participation. Increasing pluri-potency of the device beyond viral load testing (e.g., CD4+ count test) would increase its utility. Participants suggested pairing the device with telemedicine and mobile health technologies. CONCLUSIONS: If proven effective, the home-based viral load test device will become a critical adjunct in HIV cure research and HIV care.

Participant experiences using novel home-based blood collection device for viral load testing in HIV cure trials with analytical treatment interruptions

Background: HIV cure-directed clinical trials using analytical treatment interruptions (ATIs) require participants to adhere to frequent monitoring visits for viral load tests. Novel viral load monitoring strategies are needed to decrease participant burden during ATIs.Objective: To examine acceptability of a novel home-based blood collection device for viral load testing in the context of two ongoing ATI trials in Philadelphia, PA, United States.Methods: From January 2021 to February 2022, participants completed three in-depth interviews via teleconference during their participation in an ATI: (1) within two weeks of enrollment in the device study, (2) approximately four weeks after beginning to use the device, and (3) within two weeks of the end of the ATI when ART was re-initiated. We used conventional content analysis to analyze the data.Results: We recruited 17 participants: 15 were cisgender males, 1 cisgender female, and 1 transgender woman. We observed an overall 87% success rate in drawing blood with the device from home collection and found overall high acceptance of the device. A mean of 91.5 devices per participant were used for home-based blood collection. Most PWH viewed the device as relatively convenient, painless, easy to use, and a simple solution to frequent blood draws. The main challenge encountered was the inability to completely fill up devices with blood in some cases. Most participants reported positive experiences with mailing blood samples and could see themselves using the device on a regular basis outside of ATIs.Conclusions: Our study showed participant valued the novel home-based peripheral blood collection for viral load testing in the context of ATI trials. More research will be necessary to optimize implementation of the device and to assess whether blood collected can reliably measure viral loads in the context of ATI trials.

Hepatitis C virus modulates IgG glycosylation in HIV co-infected antiretroviral therapy suppressed individuals.

OBJECTIVE: Glycosylation plays a critical role in mediating several antibody (mainly immunoglobulin G; IgG) immunological functions, including antibody-dependent cell-mediated cytotoxicity (ADCC), and anti-inflammatory activities. We investigated whether IgG glycosylation and immune profile patterns are differentially modulated in mono and dual infection using samples from untreated hepatitis C virus (HCV)-infected individuals with and without co-infection with antiretroviral therapy (ART)-suppressed HIV. DESIGN: IgG glycosylation, immune subsets, natural killer cell function, and liver enzymes were assessed in 14 HCV mono-infected and 27 ART-suppressed HIV/HCV co-infected participants naïve to HCV treatment. Historic IgG glycosylation data from 23 ART-suppressed chronically HIV-infected individuals were also used for comparisons. METHODS: Plasma IgG glycosylation was assessed using capillary electrophoresis. Whole blood was used for immune subset characterization by flow cytometry. Peripheral blood mononuclear cells were used to measure constitutive and interferon-α-induced K562 target cell lysis. Statistical analysis was performed using R (3.5.0). RESULTS: HIV/HCV had lower levels of pro-ADCC-associated nonfucosylated glycans when compared with HIV [e.g. di-sialylated A2 percentage (%): P = 0.04], and higher levels of T and myeloid cell activation/exhaustion when compared with HCV (e.g. CD3CD8CD38 %: P < 0.001). Finally, in HCV high levels of the anti-inflammatory galactosylated and sialylated glycans were associated with low plasma levels of aspartate aminotransferase (AST), low CD8 T-cell activation, and high CD8 T-cell exhaustion. CONCLUSION: HCV modulates IgG glycosylation profile in HIV co-infected individuals on suppressive ART. These results could inform on the modulation of IgG glycans in other mono and dual infections.