Sotto il Monte Giovanni XXIII, Italy
Sotto il Monte Giovanni XXIII, Italy

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Rossotti R.,ASST GOM Niguarda | Borghi V.,Infectious Diseases Clinics | Callegaro A.P.,Laboratory of Virology and Microbiology | Micheli V.,Luigi Sacco Hospital | And 7 more authors.
Journal of Clinical Virology | Year: 2016

Background PrEP with FTC/TDF has shown great efficacy in preventing new HIV infections but issues remain (low adherence, high costs, toxicity and resistance development). No data are available about the impact of circulating Resistance-Associated Mutations (RAMs) on its efficacy. Objectives describe the prevalence of FTC and/or TDF-related RAMs in Italian HIV-infected population and their potential impact on PrEP efficacy. Study design ARCA is a national database that collects data about RAMs and epidemiological correlates from sites throughout Italy; it was queried about the prevalence of these RAMs in the last decade. PrEP efficacy was adjusted for a dynamic score based on RAMs prevalence. Absolute and relative risk increases (ARI and RRI) and number needed to harm (NNH) were calculated after this score. Results the query retrieved 3579 HAART-naïve and 5781 experienced subjects. Resistance to TDF is low and more common among naïve MSM in the area of Milan (where it topped to 14.3%), without other significant differences. If good adherence is not attained, RRI for receptive anal sex increases by 16% (in naïve) and 93.4% (in experienced MSM). NNH is largely above 10000 except for having receptive anal sex with a HAART-experienced MSM on a failing treatment (970). Conclusions according to this model, PrEP may be introduced in Italy without general concerns, but efficacy may be partly reduced in young MSM having sex in Rome and Milan. © 2016 Elsevier B.V.

Maggiolo F.,ASST Papa Giovanni XXIII | Di Filippo E.,ASST Papa Giovanni XXIII | Valenti D.,ASST Papa Giovanni XXIII | Ortega P.S.,Laboratory of Virology and Microbiology | Callegaro A.,Laboratory of Virology and Microbiology
Journal of Acquired Immune Deficiency Syndromes | Year: 2016

Dual treatments could help clinicians to avoid drawbacks and toxicities due to the nucleosidic backbone, while maintaining the efficacy and convenience of robust combination antiretroviral therapy (cART). We explored the combination of rilpivirine plus boosted darunavir (DRV) as an option when switching from standard cART in patients who are virologically suppressed. In this randomized, openlabel, proof-of-concept, noninferiority trial, we recruited patients aged 18 years or older with chronic HIV-1 infection and on a stable, effective (.6 months) protease inhibitor-based cART including a nucleosidic backbone. The primary endpoint was noninferiority of the virological response between treatment groups, according to FDA snapshot approach. Sixty patients were randomly allocated to dual treatment with rilpivirine plus boosted DRV or to continue their ongoing triple treatment. Noninferiority was shown at the prespecified level of 212% both at 24 and 48 weeks. At week 24, 100% of patients in the dual arm presented a blood HIV-RNA level<50 copies per milliliter compared with 90.1% in the triple drug arm (difference 9.9%, 95% CI: 20.7 to 20.7), whereas, at 48 weeks, the same proportions were 96.7% and 93.4%, respectively (difference 3.3%, 95% CI: 27.15 to 13.5). The mean change in CD4 cell count from baseline was 6.0 cells per microliter (SD, 184) for dual treatment and 16.5 cells per microliter (SD, 142) for triple treatment. A relevant decrement in CD8+38+HLADR+ cells was observed in both arms. The reduction was, however, significantly more pronounced in the dual-therapy arm. At week 48, the CD8+38+HLADR+ cell count was 3.4% (SD, 2.2) in the dual-therapy arm and 5.2% (SD, 3.1) in the triple arm (P = 0.018). None of the patients developed severe adverse events nor had to stop treatment because of adverse events or presented grade 3-4 laboratory abnormalities. A greater reduction of bone stiffness (22.25; SD, 7.1) was observed in patients randomized to continue triple therapy compared with patients switched to dual therapy (20.32; SD, 8.8). Finally, baseline HIV-DNA content directly correlated with pre-cART viral load of patients (P = 0.021), but not with time on cART or time with HIV-RNA below 50 copies per milliliter. Independently of the study arm, patients with a n HIV-RNA level constantly above 3 copies per milliliter or showing viral blips had baseline HIV-DNA levels significantly higher (64,656 copies per 106 cells; SD, 93057) compared with patients who constantly presented a HIV-RNA level below the detection limit of 3 copies per milliliter (14,457 copies per 106 cells; SD, 14098) (P = 0.001). A rilpivirine-boosted plus ritonavirboosted DRV therapy was not inferior over 48 weeks to a standard boosted protease inhibitor-based triple cART. The dual therapy did not negatively affect lipid profile and renal function and was more friendly on bone metabolism. This approach constitutes an alternative for patients experiencing nucleoside reverse transcriptase inhibitor- related toxicities. © Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.

PubMed | AO Papa Giovanni XXIII BergamoBergamo and Laboratory of Virology and Microbiology
Type: Journal Article | Journal: Journal of the International AIDS Society | Year: 2014

The long-term effects of an intensified induction regimen are unknown. In this pilot, randomized, prospective study we evaluate the effect of a short-term four-drugs induction regimen in patients with high baseline viral load.Naive patients with HIV-RNA>100.000 copies/ml receiving TDF+FTC+EFV+RAL (group ER) for 4 months and were then simplified to TDF+FTC+EFV. Two randomized control groups treated ab-initio with TDF+FTC+EFV (E) or TDF+FTC+RAL (R) were used.19 patients with a mean age of 38 years and mean baseline CD4 count of 334 (SD 216) cells/mcL and HIV-RNA of 5.47 log (SD 0.32) copies/mL were enrolled. No baseline significant difference was observed among groups. Early HIV-RNA reduction was significantly higher in ER compared to the other groups from week 1 to week 4 (P from 0.026 to 0.003) (figure 1), thereafter HIV-RNA values were comparable among the groups. At week 96, all patients had an HIV-RNA < 50 copies/mL, however only patients in the ER group had in all cases an HIV-RNA level < 3 copies/mL with a statistically significant difference compared to E (60%; P=0.038) and R (50%; P=0.020). At 96 weeks, CD4 cell median counts were 765 cells/mcL for ER, 600 cells/mcL for E and 771 for R (P=0.16), however patients in the ER group presented a lower proportion of activated CD4+CD38+HLADR+ cells (1.9% versus 3.9 and 3.8%) and CD8+CD38+HLADR+ cells (10.3% versus 16.8 and 16.5%) and a significantly better CD4/CD8 ratio (0.98 versus 0.53 and 0.61; P=0.03).A four-drug regimen in naive patients with high pre-therapy viral load improves early virologic response. A quick drop of HIV-RNA seems to correlate with a sustained virologic response. Although limited in time (four months), the four-drug regimens correlates with an improved immunological response as measured by the CD4/CD8 ratio or the percentage of activated CD4+ and CD8+ cells. The reasons why this happens deserve further studies. This study highlights the importance of a personalised therapy especially in high risk patients.

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