1. Introduction Results Objectives Methods Conclusion Funding
Meta analysis of HIV-1 drug resistance for the past 10 years of ART treatment in Uganda
Emmanuel Ndashimye 1, Art P1, Avino M1, Gibson R2,3, Quinones-Mateu2, Kyeyune F1, Nankya I1, Mugyenyi P1, Kityo C1, Salata R2, and Arts E2
Western
Schulich
MEDICINE & DENTISTRY
1Department of Microbiology and Immunology, Schulich School of Medicine & Dentistry University of Western Ontario, London, Ontario, Canada
2Joint Clinical Research Centre, Kampala, Uganda
Introduction
Results
By 2015, there were 36.7 million people living with Human Immunodeficiency Virus (HIV) infection worldwide.
2.1 million new acquired HIV infections diagnosed in the same year.
Much of HIV drug resistance research has been done in HIV subtype B and less in Non-B subtypes which represent more than 90% of HIV-1 epidemic.
Uganda is among one of the countries with highest burden of HIV infections in the world with 7.1% prevalence.
Of 33 million people in Uganda, 1.5 million have HIV infection and only 57% of patients are on ART
In Uganda the majority of HIV infections are caused by subtype A and D
Figure 4. HIV-1 subtype distribution in patients failing on first and second line therapy
Overall, 4806 sequences were analyzed and 2045 (42%) genotypes were subtype-A, 1535 (32%) subtype D, 125 (2.5%) subtype-C, 354 (7.4%) recombinant AD, and 747 (15%) had other CRFs.
No evidence of significant differences between first line and second line HIV subtype distribution in this population
Fig 1. Major drug resistance mutations in RT region
In first line failures, as expected the majority of patients had M184V/I (28%), T215Y/F (10%), K70R (7.1%) and 5.1% of patients had M41L.
In NNRTIs, the most frequent mutations were K103N/S (15%), G190A/S (9.2%) and Y181C/I/V (9.3%). The high frequent use of NVP and EFV could explain high frequency of K103N/S and G190A/S mutations, however high numbers of Y181C/I/V are worrying since ETR and RVP are commonly used as salvage therapies.
Objectives
To assess HIV drug resistance trends in Uganda population over the 10 year period
Identify the most prevalent drug resistance mutations against Reverse transcriptase inhibitors and Protease inhibitors.
Look at the impact of HIV subtype on viral suppression and general ART treatment response .
Fig 5. HIV-1 subtype in patients with PR drug resistant mutations
HIV-1 Subtype D was highly associated with treatment failure and drug resistance compared to subtype A in this population
Methods
Conclusion
This was a retrospective study which analyzed genotypic drug resistance data of HIV-1 infected patients failing on first line and second line regimens receiving treatment at Joint Clinical Research Center, Kampala, Uganda.
Patients had virological failure based on minimum viral load of 1,000 copies/ml
We analyzed reverse transcriptase (RT) and the protease (PR) regions and HIV subtype data of 4806 samples collected from 2006 to 2016.
Standard Sanger genotyping assay was performed at Center for AIDS Research Center (CFAR) laboratory which is WHO and NIH-VQA certified using ABI 3730xl DNA analyzer using in house-house assay for amplifying RT region (codon ) and PR region (codon 1-99).
HIV-1 Subtype was predicted using Scueal subtype classification algorithm and phylogenetic trees viewed in Fig tree v Drug resistance mutations (DRMs) were defined using Stanford mutation list and IAS-USA 2015 mutation list. Drug susceptibility was predicted using Stanford algorithm using Stanford HIV database version 8.2
Fig 2. Major drug resistance mutations in PR region
We observe relatively high level of HIV drug resistance in patients failing on first line than in second line regimen.
HIV subtype distribution is more the same in first line and second line failures but with treatment failure mainly associated with subtype D virus.
We show that primary HIV drug resistance in Uganda to be 10%. Even with the roll out of ART, the burden of drug resistance is still a major challenge
There is evidence of association between HIV-1 subtype and viral suppression
In patients failing on second line therapy (Lopinavir/Ritonavir based), the majority of patients had I54L/T/A/M (14.12%), M46I/L (9.82%), and V82A/S/F (9.0%).
Funding
Dr. Eric J Arts NIH-NIAID grant
Fig 3. HIV-1 drug resistance by drug
Acknowledgement
We found 3TC and FTC to be highly associated with drug resistance, most likely because of the predominant M184V mutation.
In NNRTIs, resistance was highly associated with NVP and EFV, and less with ETR and RVP which are used in salvage therapy combination.
TDF which is now a preferred regimen due to its simplification, was lesser associated with resistance compared to other NRTIs
Joint Clinical Research Centre, Kampala, Uganda and Center For AIDS Research (CFAR) Laboratories, Kampala, Uganda
Department of Microbiology and Immunology, Schulich School of Medicine & Dentistry University of Western Ontario, London, Ontario, Canada