U.M. Parikh * (1), L. Kudrick (1), L. Levy (2), E. Bosek (3), B. Chohan (4,5), N. Ndlovu (6), I. Mahaka (6), A. Hettema (7), S. Mullick (8), K. McCormick (1), C. Wallis (9), L. Wiesner (10), P. Anderson (11), I. Mukui (12), S. Masyuko (13), M. Mugambi (13), O. Mugurungi (14), G. Ncube (14), M. Dunbar (15), N.A. Dlamini (16), S. Matse (16), J. Peterson (2), J. Baeten (4,17), C. Celum (4), B. Richardson (4), D. Castor (18), K. Torjesen (2), J.W Mellors (1), Global Evaluation of Microbicide Sensitivity (GEMS) Project - (1) University of Pittsburgh, Pittsburgh, United States, (2) FHI360, Durham, United States, (3) Consultant, Nairobi, Kenya, (4) University of Washington, Seattle, United States, (5) KEMRI, Nairobi, Kenya, (6) Pangaea Zimbabwe AIDS Trust, Harare, Zimbabwe, (7) Consultant, Mbabane, Eswatini, (8) The Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, (9) BARC-SA/Lancet Laboratories, Johannesburg, South Africa, (10) University of Cape Town, Cape Town, South Africa, (11) University of Colorado, Denver, United States, (12) Ministry of Health, Nairobi, Kenya, (13) National AIDS and STI Control Programme, Nairobi, Kenya, (14) Ministry of Health and Child Care, Harare, Zimbabwe, (15) Consultant, Oakland, United States, (16) Ministry of Health, Mbabane, Eswatini, (17) Gilead Sciences, Foster City, United States, (18) Columbia University, New York, United States
BACKGROUND: The ongoing rollout of oral TDF-based PrEP has the potential to reduce HIV incidence in Sub-Saharan Africa (SSA) but HIV drug resistance (HIVDR) in PrEP breakthrough infections could threaten treatment effectiveness, contribute to spread of resistance, and undermine efforts to control HIV. Accordingly, the Global Evaluation of Microbicide Sensitivity (GEMS) project was established to monitor HIVDR in PrEP rollout programs in SSA.
METHODS: USAID/PEPFAR-supported GEMS implemented resistance monitoring in PrEP users diagnosed with HIV while participating in national PrEP programs in Kenya, Zimbabwe and Eswatini, or rollout projects in South Africa. Blood samples were collected from consenting participants diagnosed with HIV on PrEP. Demographics and self-reported adherence were collected via questionnaire. Tenofovir-diphosphate (TFV-DP) levels were measured by liquid chromatography'mass spectrometry. HIVDR mutations were detected by population genotyping and analyzed using Stanford HIVdb v9.0.
RESULTS: Of 204 reported seroconversions on PrEP, 175 (86%) participants provided a sample, including 72 (41%) from South Africa, 58 (33%) from Kenya, 28 (16%) from Zimbabwe and 17 (10%) from Eswatini. These 175 participants had a median age of 24 years (range 16-67) and 74% were female. Key populations included HIV serodiscordant partnerships (21%), female sex workers (10%), men who have sex with men (9%), and transgender individuals (6%). 26% of infections occurred within 60 days of PrEP initiation. TFV-DP was detectable ('¥31.25 fmol/punch) in 63 of 86 (73%) samples, with 49 of those 63 (78%) self-reporting good/fair adherence. 104 (59%) samples were successfully genotyped; insufficient HIV RNA (35% of all samples) was the predominant reason for no result. At least one major HIVDR mutation was detected in 47 (45%) samples, including 3TC/FTC-associated M184IV (21%), TDF-associated K65R (3%) and K70EN (3%). Transmitted NNRTI mutations unrelated to PrEP included K101E (1%), K103NS (13%), V106IM (5%), Y181C (2%), and G190A (7%).
CONCLUSIONS: The high frequency of HIV drug resistance in HIV-infected individuals on PrEP (21% with M184IV; 3% with K65R) exceeds background levels of transmitted nucleoside/tide resistance in SSA ('¤5%). Improved identification of acute infection before initiating PrEP, and HIVDR monitoring on PrEP is essential for PrEP rollout programs to preserve antiretroviral options for both treatment and prevention.