Times Live Blog: Promising results in blocking HIV during first days of infection: M2010
Vaginal gel shows promise in monkeys
By Henry Neondo (ASNS) 23 May 2010: Researchers testing a vaginal microbicide based on a new type of anti-HIV drug found it provided monkeys significant protection against simian/human immunodeficiency virus (SHIV) – a combination of HIV and a related monkey virus, a virus similar to HIV, according to a study reported at the International Microbicides Conference in Pittsburgh, Sunday.
The study is the first of a gel with an integrase inhibitor, one of the latest additions to the arsenal of drugs for the treatment of HIV but just one of the many compounds or drug combinations that researchers are hoping will be a stronghold for HIV prevention.
Charles Dobard, Ph.D., and Walid Heneine, Ph.D., of the U.S. Centers for Disease Control and Prevention said the study is the first of a gel with an integrase inhibitor, and these results support further evaluation of integrase inhibitors to examine whether they can be used to prevent transmission of HIV in uninfected individuals, in addition to their current use as treatment for HIV-infected individuals.
These include different types of antiretrovirals (ARVs) than those
currently being evaluated in clinical trials of ARV-based microbicides
or oral pre-exposure prophylaxis (PrEP).
Integrase inhibitors, the latest weapon in the HIV treatment
armamentarium, stop HIV from incorporating its genetic information into
the DNA of an infected T cell, essentially heading off HIV’s master
plan to hijack all future generations of cells.
They are intended to be used in combination with other ARVs that target different steps in the HIV life cycle.
Studies have found that integrase inhibitors can suppress virus that is resistant to some of these other ARVs, including those in a class called nucleoside/nucleotide reverse transcriptase inhibitors.
Microbicides are substances designed to prevent the sexual
transmission of HIV when applied topically on the inside of the rectum
or vagina, whereas oral PrEP is an approach involving the use of ARVs
drugs by HIV-negative people to reduce their risk of acquiring
HIV.
PrEP trials are focused on two drugs, tenofovir and Truvada ,® from a
class of ARVs called nucleoside/nucleotide reverse transcriptase
inhibitors (NRTIs).
The roster of ongoing microbicide trials are of gels that containing tenofovir, dapivirine or UC781. Dapivirine and UC781 are non-nucleoside reverse transcriptase inhibitors, a close cousin to the NRTI class of ARVs.
The researchers tested the ability of the compound L-870812 to protect against infection with SHIV.
The gel was applied vaginally to three pigtailed macaques twice a week for seven weeks. Thirty minutes after each gel application, the animals were exposed to SHIV, for a total of 14 “challenges.” A fourth animal received a placebo gel in the same manner.
Two of the three macaques receiving the active gel remained uninfected after seven weeks of being exposed to SHIV.
The third macaque became infected after seven challenges, while the macaque that received a placebo gel became infected after the third exposure. Importantly, the animal that became infected while using the active gel had no evidence of drug resistant virus even after continuing the gel regimen for an additional 15 weeks.
This is significant because one of the concerns with ARV-containing gels is that the inadvertent use of these gels in someone who is HIV-infected could allow the virus to become resistant and limit treatment options in the future.
While the results are promising, additional studies will be needed before deciding whether to advance this particular vaginal gel to trials in humans.