A switch to maraviroc due to poor tolerance of other antiretroviral drugs can be accomplished after carrying out a tropism test on pre-treatment stored blood samples, British researchers have suggested.
The research team, lead by Dr Laura Waters at London’s Chelsea and Westminster Hospital, found that few patients experience a change in their HIV co-receptor tropism once they have achieved an undetectable viral load.
Their findings are reported in the March 1st edition of Clinical Infectious Diseases.
“Trofile testing of stored samples, in combination with clinical history, can reliably predict tropism in patients receiving suppressive HAART [highly active antiretroviral therapy],” comment the investigators.
Side-effects are one of the main reasons why patients change antiretroviral therapy. An attractive option for patients who need to switch treatment is maraviroc (Celsentri). It has a mild side-effect profile and results from clinical trials show that the drug can be effective in patients starting HIV therapy for the first time, as well as in those who have previous experience of anti-HIV drugs.
However, maraviroc only works in patients whose HIV uses the CCR5 co-receptor on CD4 cells. Outcomes of maraviroc therapy are poor in patients with the CXCR4 co-receptor, which is generally confined to individuals with more advanced HIV disease or extensive experience of antiretroviral treatment.
Tropism tests are used to determine which co-receptor a patient’s HIV uses. However, these tests can only be used if a patient has a detectable viral load, and are therefore of limited use for individuals who need to change HIV therapy because of side-effects when their viral load is undetectable.
The investigators at the Chelsea and Westminster Hospital hypothesised that tropism would rarely change if a patient was taking a combination of antiretrovirals that suppressed viral load to undetectable levels. They therefore believed that analysing stored blood samples taken before a patient started HIV therapy would accurately show which co-receptor was used by an individual’s HIV.
To test this hypothesis they designed a study involving 37 patients who interrupted HIV therapy. Most of these patients took a treatment break because of side-effects. The co-receptor used before the initiation of suppressive HIV therapy was compared to that used by the virus after viral load had risen to detectable levels during the treatment break.
Most of the patients were men, and the mean duration of suppressive therapy prior to the interruption was 862 days.
Tropism tests were successful for 26 patients. The investigators were concerned that amplification failed for 26% of patients, and acknowledge that this high rate of failure was a limitation of their study.
A total of 18 patients had CCR5-tropic virus prior to the initiation of suppressive therapy.
These patients had higher baseline and nadir CD4 cell counts than individuals whose virus used the CXCR4 co-receptor.
As expected, patients with baseline CCR5 virus had less experience of HIV therapy than those with CXCR4 virus (median number of combination 1 vs. 5) and fewer virological failures (median 0 vs. 2).
The results of tropism tests performed during the treatment interruption showed that only two patients experienced a change in co-receptor during suppressive therapy.
One patient switched from CCR5 to CXCR4 virus, and the other individual experienced a change from CXCR4 to CCR5 virus.
“Tropism change is uncommon during period of viral suppression,” conclude the researchers.
Waters L et al. The evolution of coreceptor tropism in HIV-infected patients interrupting suppressive antiretroviral therapy. Clin Infect Dis 52: 671-74, 2011 (click here for the free abstract).