Project Lead(s): Julie Lajoie
Issue
Globally, HIV is most commonly transmitted through heterosexual sex, and women bear the brunt of the pandemic as, in Africa, two-thirds of new infections are among women.
Female sex workers are considered a highly vulnerable group and, despite prevention efforts, HIV incidence remains very high.
Despite being intensely exposed to HIV, studies have described a small group of sex workers in Kenya who remain HIV uninfected and are called HIV-exposed seronegative (HESN).
Their immune system has a special phenotype called Immune Quiescence, characterized by fewer HIV target cells in the female genital tract.
Solution
The project was built on work the project team has done over several years to better understand this natural protection to HIV infection.
Earlier research showed that, in HESN individuals, the basal level of activation of their immune system is lower than in relevant control groups.
As HIV target cells are highly activated, they migrate from the blood into the genital tract using an inflammatory process.
This project was undertaken to test whether preventing HIV target cells from moving into the genital tract would help reduce the likelihood of infection.
The hypothesis was that it is possible to induce the immune quiescence phenotype and prevent HIV infection.
The team wanted to determine if oral administration of inexpensive and safe anti-inflammatory drugs, such as hydroxychloroquine and acetylsalicylic acid, could induce this phenotype and potentially reduce the risk of acquiring HIV infection.
A total of 106 HIV-negative, low-risk women from Kenya were recruited and enrolled in the study for a duration of three months.
They were then given oral daily acetylsalicylic acid (ASA) (81mg/day) or hydroxychloroquine (HCQ) (200mg/day) for two months.
The study compared their level of immune activation at visit one prior to starting taking the drug (baseline) to two subsequent visits while on the drug regimen.
Outcome
This is the first study ever to show that oral administration of anti-inflammatory drugs can decrease the number of HIV target cells in the blood and the female genital tract, potentially reducing the risk of HIV infection.
Preliminary results indicate that, in both the acetylsalicylic acid (ASA) and hydroxychloroquine (HCQ) arms, a one-month oral drug administration significantly reduces the density of the HIV coreceptors (CCR5) on CD4+ T cells in the blood.
Furthermore, ASA significantly decreases the number of HIV target cells (CD4+CCR5+T cells) in the female genital tract by 35%.
The findings support the hypothesis that the T cell Immune Quiescence can be induced using anti-inflammatory drugs and that ASA may be useful to help HIV prevention.
The ability to modulate lymphocyte activation in the genital tract could be an important avenue in developing a novel anti-HIV intervention.
The team wants to apply for Phase II Transition To Scale funding to initiate a full clinical trial to confirm these earlier findings.