Differences in HIV Markers between Infected Individuals Treated with Different ART Regimens: Implications for the Persistence of Viral Reservoirs

Darcis, Gilles; Berkhout, Ben; Pasternak, Alexander

doi:10.3390/v12050489

Cited by 12 publications

(13 citation statements)

References 165 publications

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“…On average, CA RNA levels were 1.75-2-fold lower in the NNRTI-treated participants. This confirms numerous reports that measured lower residual plasma viremia in NNRTI-compared to PI-treated individuals [28]. In fact, also in this study low-level plasma HIV RNA was more frequently detectable in PI-treated than in NNRTI-treated participants, despite no difference in therapy adherence by regimen.…”

Section: Discussionsupporting

confidence: 91%

Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell-associated HIV RNA and DNA levels as compared with therapy based on protease inhibitors

Pasternak

Vroom

Kootstra

et al. 2021

Preprint

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BACKGROUND: It remains unclear whether combination antiretroviral therapy (ART) regimens differ in their ability to fully suppress HIV replication. Here, we report the results of two cross-sectional studies that compared levels of cell-associated (CA) HIV markers between individuals receiving suppressive ART containing either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). METHODS: CA HIV unspliced RNA and total HIV DNA were quantified in two cohorts (n=100, n=124) of individuals treated with triple ART regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus either a NNRTI or a PI. To compare CA HIV RNA and DNA levels between the regimens, we built multivariable models adjusting for age, gender, current and nadir CD4+ count, plasma viral load zenith, duration of virological suppression, NRTI backbone composition, low-level plasma HIV RNA detectability, and electronically measured adherence to ART. RESULTS: In both cohorts, levels of CA HIV RNA and DNA strongly correlated (rho=0.70 and rho=0.54) and both markers were lower in NNRTI-treated than in PI-treated individuals. In the multivariable analysis, CA RNA in both cohorts remained significantly reduced in NNRTI-treated individuals (p=0.02 in both cohorts), with a similar but weaker association between the ART regimen and total HIV DNA (p=0.048 and p=0.10). No differences in CA HIV RNA or DNA levels were observed between individual NNRTIs or individual PIs, but CA HIV RNA was lower in individuals treated with either nevirapine or efavirenz, compared to PI-treated individuals. CONCLUSIONS: All current classes of antiretroviral drugs only prevent infection of new cells but do not inhibit HIV RNA transcription in long-lived reservoir cells. Therefore, these differences in CA HIV RNA and DNA levels by treatment regimen suggest that NNRTIs are more potent in suppressing HIV residual replication than PIs, which may result in a smaller viral reservoir size.

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Section: Discussionsupporting

confidence: 91%

Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell-associated HIV RNA and DNA levels as compared with therapy based on protease inhibitors

Pasternak

Vroom

Kootstra

et al. 2021

Preprint

Self Cite

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show abstract

Section: Discussionsupporting

confidence: 91%

“…Consequently, finding such a difference would suggest that some regimens are more potent in suppressing residual replication than others, arguing that virus suppression is less complete with at least some of the regimens. A number of studies reported lower levels of residual viremia in individuals treated with NNRTI-based, compared to PI-based, ART regimens ( [26,27], reviewed in [28]). However, to date, few studies have compared levels of CA HIV reservoir markers between different ART regimens [29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell-associated HIV RNA and DNA levels compared to protease inhibitor-based therapy

Pasternak¹,

Vroom²,

Kootstra³

et al. 2021

eLife

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BACKGROUND: It remains unclear whether combination antiretroviral therapy (ART) regimens differ in their ability to fully suppress HIV replication. Here, we report the results of two cross-sectional studies that compared levels of cell-associated (CA) HIV markers between individuals receiving suppressive ART containing either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI).METHODS: CA HIV unspliced RNA and total HIV DNA were quantified in two cohorts (n=100, n=124) of individuals treated with triple ART regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus either a NNRTI or a PI. To compare CA HIV RNA and DNA levels between the regimens, we built multivariable models adjusting for age, gender, current and nadir CD4+ count, plasma viral load zenith, duration of virological suppression, NRTI backbone composition, low-level plasma HIV RNA detectability, and electronically-measured adherence to ART.RESULTS: In both cohorts, levels of CA HIV RNA and DNA strongly correlated (rho=0.70 and rho=0.54) and both markers were lower in NNRTI-treated than in PI-treated individuals. In the multivariable analysis, CA RNA in both cohorts remained significantly reduced in NNRTI-treated individuals (padj=0.02 in both cohorts), with a similar but weaker association between the ART regimen and total HIV DNA (padj=0.048 and padj=0.10). No differences in CA HIV RNA or DNA levels were observed between individual NNRTIs or individual PIs, but CA HIV RNA was lower in individuals treated with either nevirapine or efavirenz, compared to PI-treated individuals.CONCLUSIONS: All current classes of antiretroviral drugs only prevent infection of new cells but do not inhibit HIV RNA transcription in long-lived reservoir cells. Therefore, these differences in CA HIV RNA and DNA levels by treatment regimen suggest that NNRTIs are more potent in suppressing HIV residual replication than PIs, which may result in a smaller viral reservoir size.

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“…Author details 1 Department of Internal Medicine, Infectious and Tropical Diseases, University Clinics of Kinshasa, Kinshasa, Democratic Republic of the Congo. 2 Biostatistics and Medico-economic Information Department, University Hospital of Liege, Liège, Belgium. 3 Department of Internal Medicine and Infectious Diseases, Liège University Hospital, Liège, Belgium.…”

Section: Fundingmentioning

confidence: 99%

“…Antiretroviral therapy (ART) represents a remarkable success in recent medicine. ART radically decreases the morbidity and mortality of human immunodeficiency virus (HIV)-infected individuals and drastically reduces the risk of HIV transmission [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

Decrease in late presentation for HIV care in Kinshasa, DRC, 2006–2020

et al. 2021

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Introduction Late presentation for HIV care is a well-described issue for the success of ART outcomes and the cause of higher morbidity, mortality and further transmission. Monitoring the level of late presentation and understanding the factors associated with it would help to tailor screening and information strategies for better efficiency. We performed a retrospective cohort study in Kinshasa, the capital of the DRC. The studied population included HIV-positive adults newly enrolled in HIV care between January 2006 and June 2020 at 25 HIV urban care facilities. Patient information collected at presentation for HIV care included age, sex, WHO clinical stage and screening context. We used 2 definitions of late presentation: the WHO definition of advanced HIV disease (WHO stage 3/4 or CD4 cell count < 200 cells/mm3) and a more inclusive definition (WHO stage 3/4 or CD4 cell count < 350 cells/mm3). Results A total of 10,137 HIV-infected individuals were included in the analysis. The median age was 40 years; 68% were female. A total of 45.9% or 47.5% of the patients were late presenters, depending on the definition used. The percentage of patients with late presentation (defined as WHO stage 3/4 or CD4 cell count < 350 cells/mm3) decreased during recent years, from 70.7% in 2013 to 46.5% in 2017 and 23.4% in 2020. Age was associated with a significantly higher risk of LP (p < 0.0001). We did not observe any impact of sex. Conclusions The frequency of late presentation for care is decreasing in Kinshasa, DRC. Efforts have to be continued. In particular, the issue of late diagnosis in older individuals should be addressed.

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Differences in HIV Markers between Infected Individuals Treated with Different ART Regimens: Implications for the Persistence of Viral Reservoirs

Cited by 12 publications

References 165 publications

Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell-associated HIV RNA and DNA levels as compared with therapy based on protease inhibitors

Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell-associated HIV RNA and DNA levels as compared with therapy based on protease inhibitors

Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell-associated HIV RNA and DNA levels compared to protease inhibitor-based therapy

Decrease in late presentation for HIV care in Kinshasa, DRC, 2006–2020

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