Tropism test could show which patients would benefit from starting HIV treatment sooner

Antiretroviral-naïve patients infected with X4 or dual/mixed HIV tropisms lose CD4 cells faster than patients with CCR5 stains of HIV, and are also more likely to become ill because of HIV, according to a British study published in the May 15^th edition of Clinical Infectious Diseases. The investigators suggest that this finding could indicate that patients with X4 and dual/mixed tropism might benefit from the earlier initiation of antiretroviral therapy.

However, once antiretroviral therapy was started, patients with X4 or dual/mixed tropism, and patients with CCR5 strains of HIV, experienced comparable increases in CD4 cell count and were just as likely to achieve an undetectable viral load.

HIV uses what is called a coreceptor to bind the surface of CD4 cells. These coreceptors are described as being CCR5, CXCR4 (X4), or dual/mixed. Most patients who acquired HIV through sex initially have CCR5 strains of HIV. X4 virus is associated with a low CD4 cell count, both in patients who are treatment-naïve and treatment-experienced.

Tests called tropism assays have been developed and can accurately show if a patient has CCR5, X4, or dual/mixed virus. Investigators hypothesised that tropism testing could play a role in predicting the rate of HIV disease progression in treatment-naïve patients and help doctors and patients decide when to start antiretroviral therapy.

Doctors at London’s Chelsea and Westminster Hospital therefore looked at the tropism tests results of 402 patients. They checked changes in CD4 cell counts and rates of HIV disease progression before and after antiretroviral therapy was started. Changes in viral load after the initiation of anti-HIV drugs were also monitored.

As expected, most of the patients (326) had CCR5-tropic virus, with 73 having dual/mixed strains and only three X4 virus. The investigators were able to look at the effect of anti-HIV therapy in 229 patients with CCR5 virus and 60 patients with dual/mixed virus.

They found that patients with X4 and dual/mixed virus had significantly lower baseline CD4 cell counts than patients with CCR5 virus (203 cells/mm³ vs. 325 cells/mm³, p < 0.001). Furthermore, in the first twelve months of follow-up before anti-HIV treatment was started, patients with X4 and dual/mixed virus lost significantly more CD4 cells than patients with CCR5 virus (p = 0.026).

Patients with dual/mixed virus were significantly more likely than patients with CCR5 virus to start antiretroviral therapy with a combination that included a protease inhibitor. The investigators think that this is because they started treatment sooner, before prescribing practices changed to favour NNRTIs.

Increases in CD4 cell counts twelve months after starting antiretroviral therapy were comparable between patients with dual/mixed virus and those with CCR5 virus (182 cells/mm³ vs. 185 cells/mm³) and remained so after two years of treatment (247 cells/mm³ vs. 292 cells/mm³).

Patients with dual/mixed tropic virus and CCR5 stains were equally likely to have an undetectable viral load after six, twelve and 24 months of treatment, and the time to virological suppression was also comparable.

But the investigators found that patients with X4 or dual/mixed virus started treatment faster than those with CCR5-tropic virus (33% in first twelve months of follow-up vs. 8%, p < 0.001). Furthermore, 22% of patients with X4 or dual/mixed tropic virus experienced HIV disease progression, developing clinical illness, compared to 7% of those with CCR5-tropic strains, and this difference remained statistically significant even after the investigators had adjusted for baseline CD4 cell count and viral load (p < 0.001).

“In our cohort of treatment-naïve patients, we observed a significantly greater decrease in CD4 cell count over 12 months and significantly more clinical events in those harboring X4 or D/M-tropic HIV, compared to those harboring R5-tropic virus,” comment the investigators. They add that tropism testing “could play a role in contributing to decisions regarding the commencement of therapy.”