An Observational Retrospective Database Analysis to Evaluate Raltegravir Based-regimens, Including NUC-sparing Regimens, in Aged HIV Patients.(RalAge)
An Observational Retrospective Database Analysis to Evaluate Raltegravir Based-regimens, Including NUC-sparing Regimens, in Aged HIV Patients.(RalAge)
This is an observational retrospective cohort in real world to describe RAL data, including
 NUC-sparing regimens, in aged HIV patients. It is a phase IV study.

 90 patients will be enrolled from the Department of Public Health and Infectious Diseases of
 "Sapienza" University of Rome.

 In this retrospective analysis all naïve patients on raltegravir-based regimens and all
 patients switched to raltegravir-based regimens will be considered.
Antiretroviral therapy has changed the natural history of HIV infection. However,
 antiretroviral therapy must be maintained for life. Its potential long-term adverse effects
 may interact synergistically with the ageing process, resulting in a higher incidence of
 comorbidities. The increasing number of non-antiretroviral drugs used to treat comorbidities
 may also place the patient at a higher risk of clinically meaningful interactions. Nowadays,
 efficacy is well demonstrated by all antiretroviral drugs compared with previous times. In
 fact a substantial number of HIV-infected patients from areas where antiretroviral therapy is
 widely available have achieved sustained suppression of plasma HIV replication. In contrast,
 the contributions of antiretroviral therapy to the development and progression of
 comorbidities and to the risk of potentially severe interactions have gained increasing
 importance as HIV-infected patients are getting older. More than half of HIV-infected
 patients aged ≥ 50 years have been reported to suffer from two or more concomitant
 comorbidities. In some of these patients, maintenance of antiretroviral therapy with
 combinations including NRTIs or PIs may be challenging (1). Data on ageing HIV patients under
 antiretroviral therapy are lacking.

 RAL is considered one of the better-tolerated antiretroviral medications, due to limited side
 effects and few long-term safety concerns. Five-year clinical trial outcomes and clinical
 experience have demonstrated durable virologic suppression in both treatment-naïve and
 treatment-experienced patients, including patients with extensive antiretroviral history and
 documented antiretroviral resistance. Studies have also exhibited low adverse effect rates
 and reliable long-term safety lending to improved tolerance. Several trials have evaluated
 the reduction in adverse effects in patients switched from various antiretroviral agents to
 RAL. Treatment-naïve studies have demonstrated a lipid-neutral effect in patients on
 RAL-containing regimens. When transitioning patients from a ritonavir-boosted PI regimen,
 statistically significant decreases in total plasma cholesterol, low-density lipoprotein, and
 triglycerides were demonstrated. Given its negligible interaction with the cytochrome P450
 system, RAL displays minimal drug-drug interactions, making it a good option for ageing
 patients on multiple medications (2).

 Study Design

 This is an observational retrospective cohort in real world to describe RAL data, including
 NUC-sparing regimens, in aged HIV patients. It is a phase IV study. 90 patients will be
 enrolled from the Department of Public Health and Infectious Diseases of "Sapienza"
 University of Rome. More than 4000 HIV patients are followed at this Department of Public
 Health and Infectious Diseases of "Sapienza" University of Rome. More than 50% of these
 patients are ≥ 50 years. From 10 to 12% are treated with a raltegravir based- regimen.

 In this retrospective analysis all naïve patients on raltegravir-based regimens and all
 patients switched to raltegravir-based regimens will be considered. For raltegravir-based
 regimens we mean raltegravir as third agent in a triple regimen with NRTIs and also
 raltegravir-based regimens in NUC-sparing therapies.

 Raltegravir initiation is equivalent to baseline.

 All consecutive patients fulfilling the following inclusion criteria are considered eligible:

 -  HIV-1 infected patients,

 -  aged ≥ 60 years old

 -  naive patients receiving raltegravir based-regimen, including Nuc-sparing regimens,

 -  experienced patients with virological suppression (HIV-1 RNA<50 copies) who had switched
 from any antiretroviral drug to raltegravir-based regimens (including Nuc-sparing
 regimens) because of toxicity, convenience or other reasons.

 Data are collected from medical records. The Time horizon for patient follow-up for outcome
 is at least 12 months.

 The following information will be extracted from the database of the Department:

 -  demographics (age, sex, race)

 -  smoking

 -  risk factors for HIV infection

 -  time from HIV-1 diagnosis (years)

 -  history of AIDS diagnosis

 -  hepatitis C virus (HCV) co-infection

 -  hepatitis B virus (HBV) co-infection

 -  presence of co-morbidities (including diabetes, hypertension, CVD, CKD, cancer, etc)

 -  reasons for switching to raltegravir

 -  time with HIV-1 RNA < 50 copies/mL before switch

 -  BMI

 -  Hematology (Hb, PLT)

 -  Creatinine

 -  eGFR (CKD-EPI formula)

 -  Phosphorus

 -  Calcium

 -  AST

 -  ALT

 -  alkaline phosphatase

 -  total, direct, indirect bilirubin

 -  proteinuria

 -  total, HDL-, LDL-cholesterol

 -  triglycerides

 -  glycemia

 -  HIV-RNA

 -  CD4+, CD8, CD4/CD8 ratio since the start of raltegravir

 -  previous ART regimen and number of previous antiretroviral agents.

 Follow-up will count from the date of start of raltegravir to VF/TF or last available visit,
 whichever first occurred

 AEs were classified as mild/moderate, severe or life threatening, according to DAIDS
 Classification. AEs were considered unrelated to RAL, possibly related or related, according
 to physician criteria.

 Safety data will be descriptive; no comparison data will be analyzed.

 The primary endpoint will be the description of the proportion of participants with an HIV-1
 viral load < 50 copies/mL.

 The secondary endpoints will be:

 -  Change from Baseline in CD4+ T-cell counts, CD8 cell counts, CD4/ CD8 ratio

 -  Proportion of subjects with laboratory alterations

 -  Proportion of patients with adverse events (AE), serious adverse events (SAE), also
 according to their severity
Inclusion Criteria:

 -  signature of informed consent

 -  HIV-1 infected patients,

 -  aged ≥ 60 years old

 -  naive patients receiving raltegravir based-regimen, including Nuc-sparing regimens,

 -  experienced patients with virological suppression (HIV-1 RNA<50 copies) who had
 switched from any antiretroviral drug to raltegravir-based regimens (including
 Nuc-sparing regimens) because of toxicity, convenience or other reasons.

 Exclusion Criteria:

 - pregnancy