Maraviroc potentially useful if neurological disease is present

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Maraviroc (Celsentri) may be a good option for patients with advanced HIV disease and neurocognitive impairment, a small observation study published in the online edition of AIDS suggests.

Six patients took the CCR5 inhibitor as part of combination antiretroviral treatment, and therapeutic concentrations of the drug were detected in the cerebrospinal fluid of four individuals, and HIV viral load fell in this compartment in all patients. “This is consistent with maraviroc contributing to the inhibition of HIV-1 replication in the CNS [central nervous system]”, comment the investigators.

HIV can penetrate the central nervous system, and replication of the virus in brain is associated with the development of serious illnesses such as AIDS-dementia complex.

Glossary

cerebrospinal fluid (CSF)

The liquid surrounding the brain and spinal cord.

central nervous system (CNS)

The brain and spinal cord. CNS side-effects refer to mood changes, anxiety, dizzyness, sleep disturbance, impact on mental health, etc.

CCR5

A protein on the surface of certain immune system cells, including CD4 cells. CCR5 can act as a co-receptor (a second receptor binding site) for HIV when the virus enters a host cell. A CCR5 inhibitor is an antiretroviral medication that blocks the CCR5 co-receptor and prevents HIV from entering the cell.

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

plasma

The fluid portion of the blood.

Not all anti-HIV drugs are able to cross the blood-brain barrier, and some physicians believe that this means that the virus will be able to replicate in the central nervous system, even when a patient is taking otherwise successful antiretroviral therapy.

Most of the HIV isolated from the cerebrospinal fluids uses the CCR5 co-receptor to gain entry to cells, and this is blocked by maraviroc.

Investigators wished to evaluate the efficacy of maraviroc as part of combination antiretroviral therapy in six patients with symptoms of central nervous system disease.

These individuals had a median age of 44, and the median nadir CD4 cell count was 59 cells/mm3.

At the onset of neurological symptoms, two patients were antiretroviral-naïve, their median plasma viral load being 4.8 log10 copies/ml. The remaining four patients were taking HIV treatment, but had a detectable viral load, the median value being 2.4 log10 copies/ml.

All the patients had detectable HIV in their cerebrospinal fluid, median viral load being 3.6 log10 copies/ml.

Tropism testing revealed that five patients had virus with the CCR5 co-receptor, and all six patients added ritonavir-boosted maraviroc to their HIV treatment combination.

After one month of therapy, clinical improvements were observed in five patients. Viral load in all six individuals declined significantly in both plasma (p = 0.03) and cerebrospinal fluid (p = 0.005).

The median plasma concentration of maraviroc was 347 ng/ml. However, although two patients had good concentrations of the drug in their blood, it could not be detected in their cerebrospinal fluid. No correlation was apparent between levels of maraviroc in the blood and concentrations in cerebrospinal fluid.

“We report the effects of maraviroc-containing cART [combination antiretroviral therapy] regimens on CSF viral load in six patients with neurological symptoms. In all cases, both the HIV-1 viral load and cell count in the CSF were significantly reduced within 1 month of treatment”, write the investigators.

However, the investigators note that “all patients were receiving treatment with antiretroviral drugs other than maraviroc, including abacavir, lamivudine, and zidovudine, which are known to cross the BBB [blood brain barrier].”

Nevertheless, the investigators conclude “maraviroc should be considered in cART regimens for advanced stage AIDS patients suffering neurological disease.”

References

Melica GM et al. Maraviroc-containing regimen suppresses HIV replication in the cerebrospinal fluid of patients with neurological symptoms. AIDS, online edition, DOI: 10. 1097/QAD.0b013e32833c9353, 2010.