Authors: Amrei von Braun (1,2), Christine Sekaggya (1), Alexandra Scherrer (2,3), Brian Magambo (4), Deogratius Ssemwanga (4), Pontiano Kaleebu (4), Huldrych Günthard (2,3), Andrew Kambugu (1), Jan Fehr (2), Barbara Castelnuovo (1)

Affiliations:

  1. Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda
  2. Division of Infectious Diseases and Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
  3. Institute of Medical Virology, University of Zurich, Zurich, Switzerland
  4. MRC/UVRI Uganda Research Unit on AIDS, Entebbe Uganda

Background: Previous studies on pre-treatment drug resistance from sub-Saharan Africa have shown the highest prevalence in Uganda, particularly in Kampala, with a prevalence of 12.3%. Antiretroviral therapy (ART) has been publicly available in Uganda since 2000, with initial use – although limited – of mono/dual thymidine analogues.  This study aims to describe type and frequency of pre-treatment resistance in HIV-infected Ugandan adults seeking care at one of the largest public-sector providers in Kampala, Uganda.

Methods: From June 4th – September 30th, 2015, ART-naïve adults (³18 years) presenting to the Infectious Diseases Institute (IDI) in Kampala and willing to participate in this study, were asked to give a plasma sample for pre-treatment HIV genotyping. 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.

Results: Pre-treatment drug resistance testing was available from 152 ART-naïve HIV-infected adults, of which 96 (63.2%) were female with a median age of 33 years (interquartile range (IQR) 26-41), and a median CD4 cell count of 511 cells/uL (IQR 284-713). Mutations associated with HIV drug resistance were found in 9/152 (5.9%) patients. Five patients (5/152, 3.3%) harbored NRTI mutations, and 8/152 (5.3%) had NNRTI mutations. Five (3.3%) patients had one class mutations, and 4 (2.6%) showed double class resistance. Protease Inhibitor mutations were not observed (for specific mutations see table).

Conclusions: Contrary to previous reports we found a low prevalence of pre-treatment drug resistance among Ugandan adults in Kampala. We hypothesize that the use of mono/dual thymidine analogues in the past contributed to a higher circulation of TAMs, as observed in developed settings. The subsequent swift scale-up of triple ART in the region may have reduced pre-treatment resistance over time.

Table: Observed transmitted drug resistance mutations

Drug class / mutations Total N = 152, (%)
Any NRTI mutation

K65R

M184V

Other (M41L, T215I)

 5 (3.3)

1 (0.7)

2 (1.3)

2 (1.3)
Any NNRTI mutation

K101E

Y181C

K103N

Other (M230L, G190A/S, Y188L)

 8 (5.3)

3 (2.0)

2 (1.3)

2 (1.3)

4 (2.6)