Viro-Immunological Response of Drug-Naive HIV-1-Infected Patients Starting a First-Line Regimen with Viraemia &gt;500,000 Copies/ml in Clinical Practice

Santoro, Maria Mercedes; Carlo, Domenico Di; Armenia, Daniele; Zaccarelli, Mauro; Pinnetti, Carmela; Colafigli, Manuela; Prati, Francesca; Boschi, Andrea; Antoni, Anna Maria Degli; Lagi, Filippo; Sighinolfi, Laura; Gervasoni, Cristina; Andreoni, Massimo; Antinori, Andrea; Mussini, Cristina; Perno, Carlo Federico; Borghi, Vanni; Sterrantino, Gaetana

doi:10.3851/imp3197

Cited by 11 publications

(11 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results suggested that for patients with very high baseline HIV-RNA levels, more potent initial regimens are needed. A recent study in treatment-naïve patients with similar HIV-RNA levels demonstrated that the overall probability of viral success by 48 weeks was 80.1% on intensified regimen of 2NRTIs+PI+ INSTI, higher than other groups receiving 2NRTIs+NNRTI or 2NNRIs+PI [23]. Therefore, more potent initial treatment such as four-drug combination for patients with very high baseline HIV-RNA levels, for the purpose of achieving virologic suppression as soon as possible, should be considered.…”

Section: Discussionmentioning

confidence: 99%

Very High Baseline HIV viremia impairs efficacy of NNRTI-based ART: A long-term observation in treatment-naïve patients

Chen

Han

Song

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: High baseline HIV-RNA level (≥100,000 copies/ml) has been proved to be related with weaker virological response to antiretroviral therapy (ART). However, it was not completely clear whether a very high pre-therapy viral load (≥500,000 copies/ml) can further impair the virological response, especially in the long run. Methods: A retrospective study based on data from multicenter cohorts in China was performed. We enlisted untreated HIV infected adults recruited between18 and 65 years old, who received China’s first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. All patients had baseline HIV-RNA levels over 500 copies/ml, showed good adherence, and were followed for at least 24 weeks. Virological suppression (VS) was defined as the first HIV-RNA <50 copies/ml which lasted for six months. Virological failure was defined as any of incomplete viral suppression (HIV-RNA ≥200 copies/mL with no recorded VS within 24 weeks of treatment) and viral rebound (confirmed HIV-RNA level ≥50 copies/mL after VS). Chi-square analysis was used to compare rates of VS between different HIV-RNA strata. Kaplan–Meier analysis and Cox regression model were used to compare time to virological suppression. Logistic regression was used to evaluate odds to virological failure. Results: 758 treatment-naïve HIV patients in China were enlisted. Median follow-up time (IQR) was 144 (108-276) weeks. Most patients (68.2%) were given tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) + efavirenz (EFV) regimen. By week 48, rates of VS in three groups (<100,000, 100,000-500,000 and ≥500,000 copies/ml) were 94.1%, 85.0%, and 63.8%, respectively ( p <0.001). Very high baseline HIV viremia over 500,000 copies/ml were found to be independently associated with delayed VS [≥500,000 vs. <100,000, adjusted relative hazard (95% CI), 0.455 (0.32-0.65); p <0.001] as well as incomplete viral suppression [≥500,000 vs. <100,000, adjusted odds ratio (aOR) (95% CI), 6.084 (2.761-13.407); p <0.001] and viral rebound [≥500,000 vs. <100,000, aOR (95% CI), 3.671 (1.009-13.355), p =0.048]. Conclusion: Very high levels of pre-treatment HIV-RNA were significantly related with delayed efficacy of NNRTI-based ART and increased risk of treatment failure. More potent initial regimens should be considered for those with very high baseline viremia.

show abstract

Section: Discussionmentioning

confidence: 99%

Very High Baseline HIV viremia impairs efficacy of NNRTI-based ART: A long-term observation in treatment-naïve patients

Chen

Han

Song

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…This discrepancy might be explained by the fact that only patients with treatments including two NRTIs plus one PI or one INI or efavirenz were included in this French study. Indeed, selection might underestimate the number of patients with very high pre-cART viral load that might receive alternative treatments [10]. For this reason, in our analysis, we decided to include all patients treated with at least three drugs among at least two antiretroviral classes (regardless the recommended first-line regimens) to better represent real settings.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with documented acute infection were excluded. Analyses were performed by stratifying patients in the following pre-cART strata [9][10][11]18]: 100,000, 100,001-500,000, 500,001-1,000,000, and >1,000,000 copies/mL. Reference viremia levels (dummies) were <100,000 and 500,000-1,000,000 copies/mL in order to evaluate the risks of VR in patients with pre-cART viremia ranging 100,000-500,000 and >1,000,000 copies/mL.…”

Section: Study Populationmentioning

confidence: 99%

“…Despite the overwhelming success of the combined antiretroviral therapy (cART) [1][2][3][4], in some patients starting their first treatment, the effectiveness of cART is still not sufficient, with consequent residual viral replication and virological failure [5][6][7][8]. Studies underlined that high pre-cART plasma viral load significantly contributes to reduce the chances of HIV-1 suppression after first-line therapy [9][10][11][12]. Initial studies indicated that subjects with plasma viral load >100,000 copies/mL at cART initiation had a reduced chance of responding to treatment [13].…”

Section: Introductionmentioning

confidence: 99%

“…In fact, recent evidences highlighted that higher levels of pre-cART viral load (such as >500,000 copies/mL) are associated with a prolonged time and a lower probability of achieving VS Patients with very high pre-cART viral load induce uncertainty in clinicians' decision because treatment recommendation for this problematic category of patients are still missing [15,16]. In this context, treatments including integrase inhibitors (INIs) or even four-drugs based strategies together with ritonavir/cobicistat boosted protease inhibitors (PIbs), seem to perform better that the classical 3drug regimens based on PIs or non-nucleoside reverse transcriptase inhibitors (NNRTIs) [10,12].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Very High Pre-Therapy Viral Load is a Predictor of Virological Rebound in HIV-1-Infected Patients Starting a Modern First-Line Regimen

et al. 2018

Self Cite

View full text Add to dashboard Cite

Background: Pre-cART (combined antiretroviral therapy) plasma viral load >500,000 copies/mL has been associated with a lower probability of achieving virological suppression, while few data about its role on maintenance of virological suppression are available. In this study we aimed to clarify whether high levels of pre-cART viremia are associated with virological rebound (VR) after virological suppression.Methods: HIV-infected individuals who achieved virological suppression after first-line cART were included. VR was defined as the first of two consecutive viremia >50 copies/mL (VR50) or, in an alternative analysis, >200 copies/mL (VR200). The impact of pre-cART viremia on the risk of VR was evaluated by survival analyses.

show abstract

HIV-1 persistent viremia is frequently followed by episodes of low-level viremia

Widera

Dirks

Bleekmann

et al. 2017

Med Microbiol Immunol

View full text Add to dashboard Cite

After the start of antiretroviral therapy (ART), plasma HIV-RNA levels should fall below the limit of detection (LOD) within 24 weeks. Hence, the prolonged decline of HIV-RNA after ART initiation is defined as persistent viremia (PV). In this retrospective study, we analyzed factors associated with PV. Next-generation sequencing of viral RNA/DNA was performed to study viral evolution and the emergence of drug-resistance mutations in HIV-infected patients with PV (n = 20). In addition, HIV-DNA species, immunological parameters, and clinical data of the patients were analyzed. We found that the possible causes for PV were divers, and both virologic and host parameters of this particular cohort were heterogeneous. We identified viruses with therapy-associated DRMs in six patients (30%); two of these were detected as minority variants. Five patients had sub-optimal drug levels (25%) and the baseline plasma viral loads were relatively high. Strikingly, we observed that >40% of the PV patients finally reaching HIV levels below the LOD later on showed up with episodes of low-level viremia (LLV). However, the amount of PBMC derived HIV-DNA species was not correlated with the likelihood of LLV after PV. According to our data, we conclude that drug-resistant viruses, sub-optimal drug level, and high baseline viral loads might be probable reasons for the prolonged RNA decline only in a sub-set of patients. In the absence of emerging DRMs and/or compliance issues, the clinical implications of PV remain unclear; however, PV appears to be a risk factor for episodes of LLV.

show abstract

Viro-Immunological Response of Drug-Naive HIV-1-Infected Patients Starting a First-Line Regimen with Viraemia >500,000 Copies/ml in Clinical Practice

Abstract: In this multicentre retrospective study, patients with viraemia >500,000 copies/ml who start a first-line regimen containing PI+INI or NNRTI yield a better VS compared to those receiving a PI-based regimen.

Cited by 11 publications

References 25 publications

Very High Baseline HIV viremia impairs efficacy of NNRTI-based ART: A long-term observation in treatment-naïve patients

Very High Baseline HIV viremia impairs efficacy of NNRTI-based ART: A long-term observation in treatment-naïve patients

Very High Pre-Therapy Viral Load is a Predictor of Virological Rebound in HIV-1-Infected Patients Starting a Modern First-Line Regimen

HIV-1 persistent viremia is frequently followed by episodes of low-level viremia

Contact Info

Product

Resources

About