Fostemsavir improves virologic efficacy, immunologic response in HIV-1
The use of the investigational first-in-class attachment inhibitor fostemsavir led to improved baseline viral and CD4+ T-cell counts in patients with HIV-1 infection who had limited treatment options and were failing their current antiretroviral regimen, according to the subgroup analysis results of the BRIGHTE* study presented at AIDS 2018.
Researchers evaluated the randomized cohort of the study population comprising 272 heavily treatment-experienced participants (67 percent treated for >15 years, 75 percent exposed to ≥5 antiretroviral regimens, median age 48 years, 74 percent male) with confirmed viral load of HIV-1 RNA ≥400 copies/mL who were unable to establish a viable antiretroviral background regimen. Participants received either fostemsavir 600 mg twice/day or placebo (n=203 and 69, respectively) for 8 days on top of their failing regimen. After which, all participants received open-label fostemsavir plus optimized background therapy until week 24. [AIDS 2018, abstract THPEB045]
After the first week of treatment, fostemsavir demonstrated superior efficacy over placebo, generating a clinically significant reduction in viral load (adjusted mean log10 HIV-1 RNA, -0.79 vs -0.17 log10 copies/mL, treatment difference, -0.63, 95 percent confidence interval, -0.81 to -0.44; p<0.0001), which was similar across demographic (ie, age, gender, race, geographic region) and baseline disease subgroups (viral load and CD4+ count).
Fostemsavir use also resulted in a median decline in HIV-1 RNA of 1 log10 copies/mL among patients with baseline HIV-1 RNA >1,000 copies/mL at day 8.
Achieving a meaningful reduction in viral load in a span of one week is a promising outcome, noted the researchers, considering the participants’ limited treatment options and drug resistance.
At week 24, more than half of fostemsavir recipients (54 percent) achieved virologic suppression (HIV-1 RNA <40 copies/mL), with similar virologic response rates across all subgroups. However, lower response rates were observed among those who had a high baseline viral load and low baseline CD4+ count (38 percent with ≥100,000 copies/mL and 37 percent with <50 cells/µL, respectively) as opposed to those with low baseline viral load and high baseline CD4+ count (60 percent with <100,000 copies/mL and 63 percent with 50 cells/µL, respectively).
Regarding CD4+ T-cell count, mean increase was similar across all subgroups at week 24, ranging from 74 to 119 cells/µL (mean, 90 cells/µL), except for those with a baseline CD4+ T-cell count of <1,000 cells/µL (mean, 22 cells/µL).
Participants with a low baseline CD4+ count (<20 cells/µL) had an average increase of 97 cells/µL which, according to the researchers, is comparable in magnitude to the mean change in all other baseline CD4+ categories.
Establishing a regimen that could reduce viral load to undetectable levels and improve CD4+ count is important, as high baseline viral load and low CD4+ count increase the risk of developing comorbidities and HIV progression and transmission. [CD4, viral load, and other tests, www.aidsmap.com, accessed 6 August 2018]
These findings underscore the potential of fostemsavir in addressing the issue of antiviral resistance, which remains an unmet need in heavily treatment-experienced patients with HIV. [J Pharm Sci 2013;102:1742-1751; Infect Disord Drug Targets 2011;11:124-133]