Raltegravir, as the first
HIV integrase inhibitor, has been used and prospectively monitored since 2010 in our HIV outpatient centre, where over 1,200 patients are monitored. The aim of our report is to perform an interim assessment of the background, the safety profile and the clinical-laboratory monitoring of all patients treated with a
combination antiretroviral therapy (cART) including
raltegravir, for at least 12 months. In all, 109 pretreated patients started a
raltegravir-containing cART when aged 44.8 plus or minus 19.2 years, with a history of
HIV infection lasting 13.4 plus or minus 9.7 years. All subjects were monitored for at least 12 months (mean 17.2 plus or minus 10.3 months). In the vast majority of cases (93 of 109: 85.3%), multiple (3-16) prior cART changes prompted
raltegravir introduction in advanced-salvage lines: 72 of 109 (66.1%) patients had even developed a concurrent triple-class resistance to anti-HIV compounds. The most frequent companion
antiretroviral agents were:
darunavir/
ritonavir (75 cases),
maraviroc (47 subjects), and
etravirine (38 cases). The most common underlying conditions were:
AIDS (46 patients),
liver cirrhosis (31 cases),
AIDS-related or other
malignancies (23 cases), and major cardio-cerebro-vascular events (18 cases). A chronic HCV and HBV
hepatitis were of concern in 48 and 23 patients, respectively. The adjunct of
raltegravir favourably affected all clinical-laboratory markers of HIV
disease progression, and those of the broad spectrum of comorbidities, except for two patients who failed the
raltegravir-containing cART due to insufficient adherence. Despite the already compromised clinical situation, a minority of subjects experienced mild-transient clinical-laboratory untoward events possibly attributable to
raltegravir, such that no patients discontinued
raltegravir during the observation period. Only three
AIDS-defining conditions became apparent during
raltegravir-based cART;
chemotherapy and/or
radiotherapy cycles were performed as scheduled in patients suffering from
cancer;
chronic hepatitis B and C progressed to
liver cirrhosis and/or hepatocarcinoma in only 2 and 6 patients. Otherwise, treatment with pegylated
interferon-
ribavirin became feasible in 25 patients of 48 with chronic HCV. During
raltegravir-containing cART, neither autoimmune disorders nor novel
malignancies were diagnosed. Only mild-transient
gastrointestinal disorders,
fatigue,
dizziness,
insomnia and cutaneous
rash were reported, although their relationship with the study
drug was difficult to assess due to multiple comorbidities and
polypharmacy. Abnormal liver function testings were observed in 57 patients (52.3%), all suffering from concurrent hepato-biliary disorders. Significant increases in serum
lipids and/or
lipase levels versus baseline values were never registered: serum
lipid levels significantly improved after
raltegravir introduction. Our experience with
raltegravir underlines its excellent efficacy and safety profile, which exploits a novel mechanism of action, and displays no cross-resistance with any other antiretroviral. A progressively extended prescription in naive patients and early cART lines will allow the therapeutic potential of
raltegravir to be exploited.