Immunological and inflammatory changes after simplifying to dual therapy in virologically suppressed HIV-infected patients through week 96 in a randomized trial

Trujillo‐Rodríguez, María; Muñoz-Muela, Esperanza; Serna-Gallego, Ana; Guisado, Yusnelkis Milanés; Praena-Fernández, Juan Manuel; Álvarez-Ríos, Ana Isabel; Herrera‐Hidalgo, Laura; Dominguez, Montserrat; Lozano, Carlos Blanco; Romero-Vazquez, Gloria; Roca, Cristina; Espinosa, Núria; Gutiérrez‐Valencia, Alicia; López‐Cortés, Luis F.

doi:10.1016/j.cmi.2022.02.041

Cited by 11 publications

(4 citation statements)

References 24 publications

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“…Our group has also reported comprehensive studies on this matter without finding differences in activation, proliferation, exhaustion, senescence, and apoptosis in CD4 + and CD8 + T cells, monocyte activation, plasma levels inflammatory markers, and HIV-1-specific T-cell response or the exhaustion phenotype 96 weeks after simplifying to 2DR (DTG or DRVc plus 3TC) compared with continuing an InSTI-based 3DR ( 26 , 27 ). According to Llibre et al., if viremia remains suppressed, other factors could influence cIA/I in PHIV regardless of ART ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Long-term effects on immunological, inflammatory markers, and HIV-1 reservoir after switching to a two-drug versus maintaining a three-drug regimen based on integrase inhibitors

Saborido-Alconchel,

Serna-Gallego,

Trujillo-Rodriguez

et al. 2024

Front. Immunol.

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ObjectiveTo compare the long-term effects on immune parameters, inflammation, and HIV-1 reservoir after switching to a two-drug (2DR) versus maintaining an integrase inhibitor (InSTI)-based three-drug regimen (3DR).MethodsCross-sectional study in which HIV-1 treatment-naïve people started and maintained an InSTI-based 3DR or, at different times, switched to 2DR (dolutegravir or darunavir/cobicistat + lamivudine). CD4+ and CD8+ T-cell activation and exhaustion, plasma concentrations of hs-CRP, D-dimer, P-selectin, IL-1β, IL-6, TNF-α, IFN-γ, IP-10, sTNFR-I/II, MIP-1α/β, I-FABP, LBP, sCD14, sCD163, MCP-1, and cellular-associated HIV-1-DNA and -RNA were quantified by flow cytometry, different immunoassays, and droplet digital PCR, respectively. The U de Mann-Whitney test evaluated differences between 3DR and 2DR. Immune recovery was evaluated using a general linear model for repeated measures adjusted for different co-variables.ResultsFifty participants per group were included. The median time on 3DR was 82 months for the 3DR group and 30 months for the 2DR group, after which it switched to 2DR for a median of 57 months. We did not find differences between both groups in any of the parameters analyzed. Specifically, some values in 3DR and 2DR were hs-CRP, 0.92 mg/L (0.45–2.23) vs. 1.23 (0.61–2.38); D-dimer, 190.0 µg/L (150.0–370.0) vs. 190.0 (150.0–397.5); IL-6, 2.8 pg/mL (1.3–5.3) vs. 3.2 (2.1–4.7); sCD14, 4.5 ng/mL (3.3–6.2) vs. 5.0 (3.6–6.1), respectively, all p ≥ 0.399.ConclusionIn the long term, switching to 2DR does not negatively affect immunologic parameters, inflammatory markers, or HIV-1 reservoir.Clinical trial registrationidentifier NCT04076423.

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Section: Discussionmentioning

confidence: 99%

Long-term effects on immunological, inflammatory markers, and HIV-1 reservoir after switching to a two-drug versus maintaining a three-drug regimen based on integrase inhibitors

Saborido-Alconchel,

Serna-Gallego,

Trujillo-Rodriguez

et al. 2024

Front. Immunol.

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“…Cell-associated HIV-1 RNA quantitation. Cell-associated HIV-1 RNA was quantified from previously extracted RNA by ddPCR with the One-Step RT-ddPCR kit (Bio-Rad) using the BIO-RAD QX200 Droplet Reader, as previously reported (47). The PCR program was run according to the manufacturer's protocol using an annealing temperature of 58°C and the same primers and probes as previously described (see section HIV-1 DNA quantitation).…”

Section: Methodsmentioning

confidence: 99%

The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers

Gasca-Capote,

Lian,

Gao

et al. 2024

Journal of Clinical Investigation

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BACKGROUND. Persistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure. METHODS.The characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using nextgeneration sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq). RESULTS.PCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/ defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs.CONCLUSIONS. These results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.

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“…Antiretroviral treatment (ART) simplification with two-drug regimens (2DRs) is a strategy that may reduce drug-induced toxicity and drug–drug interactions in older patients living with HIV (PLWH) and also prevent drug-related toxicity (pre-emptive switch) in young PLWH [ 1 ]. There is robust evidence regarding the efficacy of 2DRs in maintaining a suppressed HIV viremia [ 2 ], even in terms of residual viremia [ 3 ], whereas it is less clear if 2DRs maintain the same efficacy of triple ART in improving immunological recovery and reducing immune activation [ 4 ]. Altogether, knowledge regarding 2DR treatment is reassuring, and the potential benefits in tolerability, long-term toxicities, drug interactions, cost-effectiveness, patients’ compliance, and quality of life appear to outweigh the potential risks of reducing ART class composition [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Viruses 2024, 16, 348 2 of 15 and reducing immune activation [4]. Altogether, knowledge regarding 2DR treatment is reassuring, and the potential benefits in tolerability, long-term toxicities, drug interactions, cost-effectiveness, patients' compliance, and quality of life appear to outweigh the potential risks of reducing ART class composition [5].…”

Section: Introductionmentioning

confidence: 99%

HBcAb Positivity as a Risk Factor for Missing HIV RNA Undetectability after the 3TC+DTG Switch

Malagnino,

Mulas,

Teti

et al. 2024

Viruses

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Hepatitis B Core antibody (HBcAb) positivity is the surrogate marker of hepatitis B occult infection. This condition is not a contraindication for switching to two-drug (2DR) antiretroviral therapy; however, the removal of tenofovir may contribute to poor control of HBV replication. A multicentre retrospective cohort study investigated the impact of HBcAb positivity on HIV control in patients switching to a 2DR with Lamivudine and Dolutegravir (3TC-DTG). In this study, a comparison analysis was conducted between HBcAb-positive and -negative PLWH regarding HIV-RNA suppression, considering: (1): Target Not Detected (TND) < 20 cp/mL; (2) Target Detected (TD) < 20 cp/mL; and (3) Detectable > 20 cp/mL and <50 cp/mL and >50 copies/mL. A total of 267 patients on 2DR with 3TC-DTG were included. In comparison to HBcAb-negative, HBcAb-positive patients were older (45 years [35–54]) and had a lower CD4+ nadir (248 vs. 349 cells/mmc, p = 0.007). No difference in the maintenance of virological suppression was present in the two groups of patients before the switch. Although no patient had an HIV-RNA > 20 cp/mL after the switch, significantly fewer HBcAb-positive compared with -negative subjects resulted in TND at 12, 24, and 36 months after the switch: 52 [69.3%] versus 164 [85.4%], p = 0.004, 50 [72.5%] versus 143 [89.9%], p = 0.001, and 30 [66.7%] versus 90 [92.8%], p = 0.001, respectively. HBcAb positivity is associated with an increased risk of suboptimal HIV suppression during the 36 months after 3TC/DTG simplification. This finding reinforces the relevance of the OBI condition in PLWH and raises the issue of careful virological monitoring of such cases.

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Immunological and inflammatory changes after simplifying to dual therapy in virologically suppressed HIV-infected patients through week 96 in a randomized trial

Cited by 11 publications

References 24 publications

Long-term effects on immunological, inflammatory markers, and HIV-1 reservoir after switching to a two-drug versus maintaining a three-drug regimen based on integrase inhibitors

Long-term effects on immunological, inflammatory markers, and HIV-1 reservoir after switching to a two-drug versus maintaining a three-drug regimen based on integrase inhibitors

The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers

HBcAb Positivity as a Risk Factor for Missing HIV RNA Undetectability after the 3TC+DTG Switch

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