Authors: Amrei von Braun (1,2), Alexandra Scherrer (2,3), Christine Sekaggya (1), Joseph Kirangwa (4), Deogratius Ssemwanga (4), Pontiano Kaleebu (4), Huldrych Günthard (2,3), Andrew Kambugu (1), Barbara Castelnuovo (1), Jan Fehr (2)
- Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda
- Division of Infectious Diseases and Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
- MRC/UVRI Uganda Research Unit on AIDS, Entebbe Uganda
Background: Until a recent change in guidelines, HIV-infected patients on antiretroviral therapy (ART) in Uganda were monitored using CD4 cell counts only. So far, little is known about prevalence of drug resistance among HIV-infected patients with virological failure (VF) after immunological treatment monitoring in Uganda.
Methods: From June 4th – September 30th, 2015, viral loads were done in HIV-infected adults (³18 years) on ART for at least 6 months presenting to the IDI in Kampala. In case of VF (>1000 copies/mL), HIV genotyping was requested. Sequencing of partial polymerase gene was conducted using an in-house protocol. All sequences were submitted to the Stanford University HIV Drug Resistance database and the surveillance drug resistance mutations were identified using the 2009 WHO mutations list. HIV-1 subtypes were determined using REGA version 3.0.
Results: Viral load measurements were done in 2511 patients, who had been on ART for a median time of 4.7 years (interquartile range (IQR)2.5-8.7). A total of 199 patients (7.9%) had VF with a median viral load of 4.4 log10 copies/mL (IQR:3.9-4.9). The majority of patients with VF (140,70.4%) were on first-line ART, 138(69.3%) were female, and the median age was 37 years (IQR:30-43). HIV genotyping tests were available in 163(81.9%). HIV-1 subtypes A(46%) and D(34%) were most common. Relevant drug resistance mutations were observed in 135 (82.8%), of which 103(63.2%) had resistance to two drug classes, and 11(6.8%) had resistance to all three drug classes available in Uganda.
Conclusions: With 92% of all patients virologically suppressed, the overall prevalence of VF was low, and is in-line with the third of the 90-90-90 UNAIDS targets. However, the majority of failing patients had developed resistance to more than one drug class, suggesting that failing regimens – not identified as such by CD4 monitoring – had been in place for a prolonged period of time.
Figure: Type and frequency of most prevalent resistance-associated mutations observed
Figure legend: NRTI = Nucleoside/Nucleotide Reverse Transcriptase Inhibitors; TAM = Thymidine analogue mutation; NNRTI = Non- Nucleoside/Nucleotide Reverse Transcriptase Inhibitors; PI = Protease Inhibitors;