Maintenance of virologic suppression and improvement in comorbidities after simplification to raltegravir plus boosted darunavir among treatment-experienced HIV-infected patients

Abstract

The use of two potent, well-tolerated, drugs could permit the maintenance of virologic suppression even in heavily pretreated people living with HIV. In this retrospective, multicenter, simplification study (NCT03348449), we included those patients with virologic suppression who switched to raltegravir (RAL) plus boosted darunavir (b/DRV). Overall, 345 patients (75 females, 25%) were included. Patients were largely pretreated (mean, 9.4 regimens), suppressed for a median of 41.1 months. Fifty patients had ≥1 mutation against DRV. At 96 weeks, the efficacy by intention-to-treat analysis (snapshot) was 73% (95%CI, 68.4–77.8%), but 97.1% (95%CI, 95.4–98.9) excluding changes due to non-virologic reasons, and virologic failure was rare (0.9%; 95%CI, 0.1–1.2%). Median CD4/CD8 ratio increased from 0.59 to 0.62 (p < 0.01), CD4+ cell count by +90 cells/µl (p < 0.01), and mean estimated glomerular filtration rate (eGFR) increased from 85.2 to 88.5 ml/min at 96 weeks, greater for patients receiving tenofovir disoproxil fumarate (eGFR, +3.6 ml/min, p = 0.04; serum phosphate +0.33 mg/dl; p < 0.01). There was a continued and significant improvement in the total cholesterol/high-density lipoprotein-cholesterol ratio. In conclusion, the simplification to a dual regimen with the combination of RAL and b/DRV is associated with maintenance of virologic suppression, even in largely pretreated patients, with improvements in CD4+ cell count, CD4/CD8 ratio, and in renal and lipid parameters.

HIV: the changing paradigm

“…It is becoming increasingly clear that, in carefully selected patients, dual therapy is efficacious, with potential to reduce drug toxicity and cost 36 . There is growing evidence to support a switch to dual therapy once viral suppression is maintained on a standard three‐drug regimen 34,37,38 . However, it is important to note that none of the currently available two‐drug regimens has anti‐hepatitis B virus (HBV) activity 39 .…”

“…36 There is growing evidence to support a switch to dual therapy once viral suppression is maintained on a standard three-drug regimen. 34,37,38 However, it is important to note that none of the currently available two-drug regimens has anti-hepatitis B virus (HBV) activity. 39 Thus, only select patients, specifically those without HBV coinfection and no evidence of resistance to either agent, have been included in the major trials of two-drug regimens.…”

Optimizing switching strategies to simplify antiretroviral therapy: the future of second-line from a public health perspective

“…Dual therapies for maintenance in heavily antiretroviral therapy-experienced people with HIV Drug-sparing regimens (a regimen with less than three antiretrovirals or a decrease in the expected number of drug classes) are most often recommended in maintenance treatment (optimization of an ART composition in case of stable therapeutic success) as shown in Table 3. These recommendations are based on studies conducted most often in HICs and sometimes in heavily ARTexperienced PWH (beyond second-line) with a stable undetectable HIV viral load when enrolled [60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76]. The key goals are clinical: avoid long-term toxicity (cardiometabolic, renal and bone adverse event) [67,77,78], optimize the impact on any newly diagnosed comorbidities, and minimize drug-drug interactions.…”

Selection of HIV-1 for Resistance to Fifth Generation Protease Inhibitors Reveals Two Independent Pathways to High-Level Resistance

“…While therapy has not yet moved to single agents, potent two drug therapies are being explored. In this regard, several studies have shown that a PI can be part of a successful two drug therapy regimen (Casado et al, 2020; Di Cristo et al, 2020; Hawkins et al, 2019; Huang et al, 2019; Vizcarra et al, 2020).…”