#4355 THE INFLUENCE OF ANTIRETROVIRAL DRUGS AND HIV RESISTANCE MUTATIONS ON THE SHEDDING OF HIV-1 INTO PERITONEAL DIALYSIS EFFLUENT
Teboho Mooko, Busiswa Bisiwe, Perpetual Chikobvu, Daniel Morobadi, Martin Nyaga, Phillip Bester, Gabre Kemp, Dominique Goedhals, Thabiso Mofokeng, Kwazi Ndlovu- Transplantation
- Nephrology
Abstract
Background and Aims
Antiretroviral therapy (ART) is effective HIV management even in HIV-positive patients with end-stage kidney failure (ESKF). However, drug resistance mutations are important determinants of therapeutic effects. The study aimed to determine the prevalence of HIV resistance mutations and ART drug penetration in the peritoneal compartment and their effect on the shedding of HIV-1 into continuous ambulatory peritoneal dialysis (CAPD) effluents.
Method
This prospective cross-sectional study of HIV-positive ESKF patients managed with ART and CAPD at Universitas Academic Hospital collected enrolled patients' background information and clinical and laboratory data. HIV-1 was detected using quantitative polymerase chain reaction (qPCR) and sequenced by the Sanger method, while ART levels were quantified using LC-MS/MS.
Results
There were 38 patients recruited with a median age of 41.8 (IQR, 36.15–48.0) years and were predominantly on abacavir (89.5%), lamivudine (100%) and efavirenz (76.3%) for a median duration of 8 (IQR, 6–11) years. Among participants with detectable HIV in CAPD effluents, the prevalence of ARV-drug resistance mutations was 71.4% (5/7) compared to 12.9% (4/31) among those with undetectable HIV-1 (p = 0.004) with NNRTI resistance mutations predominating. Participants with detectable HIV-1 had lower abacavir (0.00182 vs 5.68 ng/µl; p = 0.021), lamivudine (0.0152 vs 1.09 ng/µl; p = 0.001) and efavirenz (3,605 vs. 57,8 ng/µl; p = 0.004) plasma levels compared to those with undetectable HIV-1. Measured lamivudine (0.455 vs 0.342 ng/µl; p = 0.007) and efavirenz (46.5 vs 2.34 ng/µl; p<0.001) drug levels are significantly higher in plasma than CAPD effluents.
Conclusion
ART resistance mutations, lower drug levels and poor compartment penetration are suggested significant factors for HIV-1 shedding into CAPD effluents.