HIV Infections
Conditions
Brief summary
The primary objective was to determine the mean change in HIV viral load from baseline to Week 4 compared with placebo after 4 weeks of treatment in highly experienced HIV-infected patients. Secondary objectives were to determine (1) the tolerability, hematologic and hepatic safety of different doses of alovudine and (2) the effect of baseline nucleoside genotypic susceptibility on virologic response after 4 weeks of alovudine administration
Interventions
DRUGAlovudine - low
DRUGAlovudine - medium
DRUGAlovudine - high
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent before any trial procedure * HIV-1 infected males or females ≥18 years of age * Screening genotypic resistance report indicating two or more of the following nucleoside reverse transcriptase inhibitors (NRTI) resistance mutations: 41, 67, 70, 210 and 215 * Stable NRTI regimen without stavudine and zidovudine for at least 6 weeks before screening and stable antiretroviral (ARV) background treatment for 3 months before screening * HIV-1 viral load ≥1000 copies/mL and \<75,000 copies/mL at screening * Change in viral load between previous test within 3 months before screening, using local laboratory for routine tests, and screening test was \<1.0 log10 copies/mL * Acceptable medical history, as assessed by the investigator * Current stable ARV medication regimen between screening (Visit 1) and Visit 2
Exclusion criteria
* ARV medication naïve * Patients on recent drug holiday, defined as off ARV medications for at least 7 consecutive days within the previous 3 months * Female patients of child-bearing potential who : * have a positive serum pregnancy test * are breast feeding, * are planning to become pregnant, or * are not willing to use a barrier method of contraception * Prior alovudine use * Use of investigational medications within 30 days before study entry or during the trial * Use of immunomodulatory drugs within 3 months before study entry or during the trial (e.g. interferon, cyclosporine, hydroxyurea, interleukin-2) * Current use of rifampin, rifabutine, isoniazid, pyrazinamide, stavudine, zidovudine, ganciclovir, chronic use of hepatotoxic drugs, anti-tumour therapy or probenecid * Laboratory values: * Neutrophils of Grade 2 or greater abnormality * Hemoglobin of Grade 2 or greater abnormality * Platelets: Grade 2 or greater abnormality * Creatinine of ≥1.25 Upper limit of the normal (ULN) * Lipase of Grade 1 or greater abnormality * Alanine aminotransaminase (ALT) or Aspartate aminotransaminase (AST) of Grade 2 or greater abnormality * Direct bilirubin of Grade 1 or greater abnormality * CD4 ≤50 cells/mm3 * Hepatitis B (+HBsAg or +HBcAB) or C +Hepatitis C virus (+HCV AB ) co-infection, chronic hepatitis, on-going hepatitis or pancreatitis * Any new or active AIDS-defining event within 30 days before study entry * Inability to adhere to the requirements of the protocol, including active substance abuse as assessed by the investigator * In the opinion of the investigator, likely survival of less than 6 months because of underlying disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean change in HIV viral load measured from plasma samples | Up to 4 weeks after drug administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of virologic responders per treatment arm | Up to 4 weeks after drug administration | — |
| Proportion of patients experiencing a change of viral load | Up to 4 weeks after drug administration | viral load of ≥1 log10 from baseline to Week 4 |
| Mean change in CD4+ cell count | Up to 4 weeks after drug administration | — |
| Percentage of 0.5 virologic responders per treatment arm | Up to 4 weeks after drug administration | — |
| Percentage of load responders per treatment arm | Up to 4 weeks after drug administration | — |
| Number of patients with abnormal changes in laboratory parameters | Up to 4 weeks after drug administration | — |
| Number of patients with adverse events | Up to 4 weeks after drug administration | — |
| Number of patients with laboratory test abnormalities and with respect to Division of AIDS (DAIDS) grading | Up to 4 weeks after drug administration | — |
| Number of patients with serious adverse events | Up to 4 weeks after drug administration | — |
| Number of patients who discontinued due to adverse event | Up to 4 weeks after drug administration | — |
| Mean change in CD8+ cell count | Up to 4 weeks after drug administration | — |
| Percentage of 0.7 to 0.9 virologic responders per treatment arm | Up to 4 weeks after drug administration | — |
Outcome results
None listed