The use of topical tenofovir gel for HIV PrEP has been shown to reduce the incidence of HSV-2-infection by 51% in women in the Caprisa 004 Study. Oral tenofovir-based PrEP also reduced HSV-2 acquisition by 28% among heterosexual men and women in the Patrners PrEP study. No reduction of HSV-2 incidence was reported in the Iprex study among MSM with daily TDF/FTC but adherence was low. We wished to assess the impact of on demand TDF/FTC for PrEP on HSV-1/2 incidence in the ANRS IPERGAY PrEP trial among MSM.
Stored serum samples from participants enrolled in the blinded phase (TDF/FTC or placebo) of the ANRS Ipergay trial were tested at baseline and at their last visit for HSV-1 and HSV-2 antibodies using serological tests (BioPlex 2200 HSV-1 & HSV-2 IgG, Biorad). We also studied the shedding of HSV-2 in anal swab from HSV-2 seropositive patients. HSV1/HSV2 (HSV1 HSV2 VZV R-gene™ kit Argene) PCR was performed at baseline, M6 and M12.
Of the 400 participants (199 in the TDF/FTC arm and 201 in the placebo arm), 39% were tested HSV-2 sero-positive and 70% HSV-1 sero-positive at baseline. Only 18% were sero-negative for both HSV-1 and HSV-2. Of the 218 HSV-2-seronegative participants with a median follow-up of 10.2 months (IQR: 6.1-23.5), 19 (9%) acquired HSV-2 infection. Overall HSV-2 incidence was 7.6% per 100 person-years; 8.1% (95% CI: 4.0%; 14.5%) in the TDF/FTC arm versus 7.0% (95% CI: 3.0%; 13.7%) in the placebo arm (p=0.75). For HSV-1, 14/108 (13%) seronegative participants acquired HSV-1 infection after a median follow up of 10.2 months. Overal incidence of HSV-1 infection was 11.7% per 100 person-years; 16.2% (95% CI: 7.4%; 30.8%) in the TDF/FTC arm versus 7.8% (95% CI: 2.5%;18.2%) in the placebo arm ( p=0.19). Compared to participants receiving placebo, there was no difference in HSV-2 or HSV-1 sero-incidence among participants using > 15 pills/month of TDF/FTC. HSV-2 shedding was analyzed in 58 participants with available anal samples (28 in the placebo arm and 30 in the TDF/FTC arm), only 3 patients had HSV-2 positive PCR, 1 at baseline (4 900 copies/ml), 1 at M12 (115 500 copies/ml) and 1 at M6 (2 816 000 copies/ml) and M12 (595 000 copies/ml), the 2 latter being in the TDF/FTC arm.
The incidence of HSV-2 and HSV-1 was high in these high risk MSM using PrEP. On demand oral PrEP with TDF/FTC failed to reduce HSV-1/2 incidence in this population.