Raltegravir plus lamivudine as ‘maintenance therapy’ in suppressed HIV-1-infected patients in real-life settings

Sir, We read with great interest the article by Gubavu et al.1 on dolutegravir-based monotherapy and dual therapy as maintenance therapy in highly experienced HIV-1-infected patients. They examined 21 patients receiving dolutegravir as monotherapy and 31 patients receiving dolutegravir as dual therapy. At the last follow-up visit, 100% and 97% of patients showed undetectable plasma viral load, respectively, with a median follow-up of 32 and 50 weeks, respectively. They concluded that these regimens are safe and proved effective for immunovirological control. In the literature, there are no data about raltegravir plus lamivudine as maintenance ART. So we would like to report our clinical experience in 14 HIV-1-infected patients who switched to 400 mg of raltegravir every 12 h plus 300 mg of lamivudine every 24 h from other regimens, followed at the Infectious Disease Outpatient Department of G.B. Rossi Hospital in Verona, Italy, and at the Clinic of Infectious Diseases of University of Bologna at S.Orsola-Malpighi Hospital in Bologna, Italy. All these patients had been virologically suppressed for at least 18 months, with a mean of 47.1 months (range 18–190 months), never failed and they had no resistance mutations for lamivudine or raltegravir on the genotypic test; their nadir CD4 count was >200 cells/mm3 (range 202–446 cells/mm3) and they had experienced a maximum of two past therapeutic regimens. The mean age was 48.6 years (range 30–74 years). At baseline the mean CD4 count was 685 cells/mm3 and at the last visit it was 768 cells/mm3 (Table 1). Age, gender, first and second HAART regimens, months of virological suppression pre-switch, months on lamivudine plus raltegravir, HIV RNA at the last visit and CD4 count at baseline and at the last visit 3TC, lamivudine; RAL, raltegravir; TDF, tenofovir disoproxil fumarate; FTC, emtricitabine; ATV/r, atazanavir/ritonavir; EFV, efavirenz; ZDV, zidovudine; ABC, abacavir; FVP/r, fosamprenavir/ritonavir; NVP, nevirapine; LPV/r, lopinavir/ritonavir; FVP, fosamprenavir; DRV/r, darunavir/ritonavir; ND, not detectable. Age, gender, first and second HAART regimens, months of virological suppression pre-switch, months on lamivudine plus raltegravir, HIV RNA at the last visit and CD4 count at baseline and at the last visit 3TC, lamivudine; RAL, raltegravir; TDF, tenofovir disoproxil fumarate; FTC, emtricitabine; ATV/r, atazanavir/ritonavir; EFV, efavirenz; ZDV, zidovudine; ABC, abacavir; FVP/r, fosamprenavir/ritonavir; NVP, nevirapine; LPV/r, lopinavir/ritonavir; FVP, fosamprenavir; DRV/r, darunavir/ritonavir; ND, not detectable. In this retrospective observational study, the primary endpoint was the proportion of patients who maintained virological suppression (HIV RNA <20 copies/mL or not detectable) at the last follow-up visit; then we looked retrospectively if the deintensification had led to improvements in the lipid, renal and liver profiles. The reason for switching was essentially NRTI toxicity – both ongoing and to prevent it (four patients were on abacavir, one patient was on zidovudine and nine patients were on tenofovir disoproxil fumarate). In 10 patients raltegravir was given once daily. In December 2016 all 14 patients maintained virological suppression (HIV RNA <20 copies/mL or not detectable) at the last follow-up visit. The mean follow-up time was 13.8 months (range 6–31 months). No patient interrupted treatment due to intolerance or any laboratory-related adverse event. In particular, the mean values for lipids (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides), ALT, creatine phosphokinase and glycaemia did not significantly change from baseline to the last visit. For statistical analysis, we used Student’s t-test for paired samples to analyse differences in mean values from baseline to both 6 and 12 months after the switch. The mean serum creatinine significantly decreased statistically (P < 0.05) from baseline (mean value 1.05 mg/dL) up to 6 months (mean value 0.98 mg/dL) or 12 months (mean value 0.96 mg/dL) after the switch, most likely due to the removal of tenofovir disoproxil fumarate. Currently, comorbidities are common among HIV-infected patients and increase with age. Furthermore, the increasing number of non-antiretroviral drugs used to treat these comorbidities may also place the patient at higher risk of clinically meaningful interactions. Therefore, in the era of NRTI sparing and boosted-PI-free ART, the class of integrase strand transfer inhibitors has been increasingly recognized not only as the first-line option, but also as the backbone of maintenance lightened regimens. We are waiting for the results of the RALAM study, a pilot 24 week open-label, randomized, controlled clinical trial of dual therapy with raltegravir/lamivudine, replacing standard combination ART. This trial started in January 2015 and the final data collection date for the primary outcome was December 2016. The trial’s aim is to assess the safety, tolerability and efficacy of this dual therapy.2 Our main limitation is the small number of patients involved in this study. However, we believe that dual therapy with raltegravir plus lamivudine as ‘maintenance therapy’ in selected suppressed patients could be safe, well tolerated and a proven effective strategy to reduce the long-term side effects and costs of combination ART. For these reasons, we think that this regimen should be explored in randomized clinical trials. This study was carried out as part of our routine work. None to declare.