番茄社区

Remdesivir (Veklury) was originally developed as a treatment for Ebola virus infection and, despite having failed in an earlier trial, may now have found its niche there.

In a phase II study conducted in West Africa, the drug reduced Ebola viral matter in the semen of male survivors, according to Dehkontee Gayedyu-Dennis, MD, of the Partnership for Research on Vaccines and Infectious Diseases in Paynesville, Liberia, speaking at the .

Persistence of Ebola virus in survivors' semen remains a significant problem in West Africa, where their sexual partners face continuing risk of infection. Ebola cases arising in this way began appearing shortly after the major 2013-2014 outbreak was declared over, and have continued to crop up since. It will most likely be a problem in the Democratic Republic of the Congo as well, which with the disease.

Studies in Ebola survivors have found viral RNA in semen for as long as 40 months after resolution of clinical illness, Gayedyu-Dennis explained. (And not only in semen, but also in other "immune privileged" tissues such as the eyes and central nervous system.)

A previous ended in disappointment (two monoclonal antibody cocktails proved superior), but a small primate study indicated that drug concentrations were particularly high in the testes and epididymis -- greater than in general circulation, in fact, Gayedyu-Dennis said. With the drug appearing reasonably safe, a clinical trial to determine whether it would reduce viral loads in semen appeared reasonable.

Results in this trial, with a total of , indicated that the drug was at least modestly effective.

Participants' semen was increasingly negative for Ebola RNA, as evaluated with a measure called "assay negativity rate" (ANR) 2 to 6 months after treatment. ANR is the ratio of negative semen samples to all samples tested, thus ranging from 0 (all samples positive) to 1 (all samples negative).

Mean ANR values during the 2-6 month follow-up were 0.96 among the 20 participants receiving remdesivir, versus 0.81 in 18 men assigned to placebo (P=0.041).

In the early phase following treatment (days 3-28 after the last infusion), remdesivir showed a nonsignificant trend toward better efficacy, with mean ANR of 0.85 versus 0.76 for placebo.

Remdesivir's efficacy was clearest in the subset of seven participants whose two baseline samples were positive for Ebola: all four assigned to remdesivir had no positive samples during the 2-6 month follow-up, whereas the mean ANR among the three participants receiving placebo was 0.33, indicating most samples remained positive (P=0.028).

In contrast, there was no difference in ANR values between treatment arms at any time point for participants who had one positive and one negative sample at baseline -- perhaps reflecting lower viral loads.

Gayedyu-Dennis said this difference in efficacy according to baseline positivity "makes sense, given that remdesivir acts by inhibiting viral replication."

Overall, she said, the results justify a larger trial to confirm clinical efficacy and pave the way for wider use in Ebola survivors.

Comment