Treatment with CCR5 antagonists: which patient may have a benefit?
The concept of CCR5 antagonists introduces an additional molecular target. Maraviroc (MVR) is approved by the FDA for use in HIV-1 infected patients for combination antiretroviral treatment of adults infected with only CCR5-tropic HIV-1 who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents. Tropism and treatment history should guide the use of MVR. Data from clinical trials show significant efficacy of MVR for patients with pre-treatment and multiple class failure. Additional clinical data show a CD4 reconstitution that is more pronounced than with comparator in treatment naive and in late stage patients even without CCR5-tropic virus indicating patients in earlier stages and even patients without CCR5 testing will benefit from MVR. MVR is not licensed for treatment naive patients but it has a high potential for further development in this patient group. It shows better immunological reconstitution than efavirenz. Pooled safety data from all available trials shows good short term tolerability. Caution is needed in hepatitis co-infection with pre-existing liver damage and in patients with heart failure. Isolates from different geographic regions differ in coreceptor usage. Summarizing knowledge on HIV-1 subtypes and CCR5 tropism shows that in principle all subtypes are susceptible to MVR. However, in subtypes A and D dualtropic and alternative coreceptor use were found. Clinical efficacy in patients from regions with A and D predominance should be studied in future trials. In conclusion, MVR will be of benefit for patients in various treatment situations and regions.
Mueller
M C
MC
Department of Infectious Diseases, Med. Poliklinik, University Hospital of Munich, Campus Innenstadt, Pettenkoferstr. 8a, 80336 Munich, Germany.
Bogner
J R
JR
D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D000077592:Maraviroc; D018579:Patient Selection; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D044966:Anti-Retroviral Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc