HIV-1 drug resistance in a rural HIV clinic in Coastal Kenya. Amin Hassan KEMRI/Wellcome Trust Research Programme, Kilifi, Kenya 22 nd November 2013

Layout Background Objective Methods Results Summary Acknowledgement 12/06/2014HIV-1 drug resistance in Kenya2

HIV in Kenya Generalized HIV epidemic – Prevalence, 5.6% (Kenya AIDS Indicator Survey 2012) – People living with HIV, 1.6 million in 2011 (AIDS Epidemic Update 2011) Scale up of antiretroviral therapy – (2003) to ~ (2012); 72% coverage (UNAIDS 2012) – Reduction in HIV-related morbidity and mortality – Emergence and transmission of HIVDR 12/06/2014HIV-1 drug resistance in Kenya3

HIVDR in Kenya Transmitted HIVDR: – Initially, low levels of <5% (Hamers R. et al, 2011; Price M. et al, 2011) – Recently, high prevalence: 9/68 (13.2%) (Sigaloff K. et al, 2012) Acquired HIVDR: – Overall prevalence: 14/132 (10.6%) (Steegen K et al, 2009) – Predominant mutations: M184V, K103N Paucity of HIVDR data from rural Kenya 12/06/2014HIV-1 drug resistance in Kenya4

Objective To describe HIV-1 transmitted and acquired drug resistance in a rural HIV clinic in Coastal Kenya. 12/06/2014HIV-1 drug resistance in Kenya5

Study site 12/06/2014HIV-1 drug resistance in Kenya6

Study setting Standardised public health approach – ART eligibility: CD4 count <350 and/or WHO stage III/IV – First line: 2 NRTIs + 1 NNRTI – Second line: 2 NRTIs + boosted PI – Routine monitoring: Clinical and Immunological – Targeted monitoring: Virological and Drug resistance testing 12/06/2014HIV-1 drug resistance in Kenya7

Study design Cross sectional surveys, 2008 – 2011 Eligibility: – Adults (>15 years) – Transmitted HIVDR: ART naïve, enrolling for HIV care – Acquired HIVDR: on 1st line ART, >6 months Use of remnant samples from routine CD4 counts 12/06/2014HIV-1 drug resistance in Kenya8

Laboratory methods Plasma viral load quantification: – In house assay, viremia >400 cpm HIVDR genotyping: – In-house assay (Cane P., 2011) – Amplified and sequenced pol region – Sequences submitted to Stanford HIVDR database – TDR: WHO list for surveillance of TDR 12/06/2014HIV-1 drug resistance in Kenya9

Transmitted HIVDR (N=182) Females: 138 (76%) Mean age: 35 years Transmitted HIVDR: 2/182, 1.1% (95% CI, 0.1 – 3.9) 12/06/2014HIV-1 drug resistance in Kenya10 MutationDrug ClassSubtypeGenderAge (years) T215DNRTIA1Female16.4 M46LPIA1Female22.9

Viremia and Acquired HIVDR (N=232) Median duration on ART: 14 months (IQR: ) HIV-1 Viremia: 25% (95% CI: ) Acquired HIVDR: 13% (95% CI: ) 12/06/2014HIV-1 drug resistance in Kenya11

Acquired HIVDR mutations (N=29) 6/12/2014HIV-1 drug resistance in Kenya12 Dual-class resistance, n= 25 (86%)

Correlates of Viremia, Acquired DR (N=232) CorrelateCategories*Adjusted OR (95% CI)LRT p-value Adherence Satisfactory ( 95%) Unsatisfactory (< 95%) Reference 3.0 (1.5 – 6.5)0.003 Age group (years)15.0 – Reference 0.3 (0.2 – 0.5) /06/2014HIV-1 drug resistance in Kenya13 *Adjusted for gender, marital status, education status, baseline regimen, drug substitution and duration on ART.

Viremia and Acquired HIVDR by age (N=232) 12/06/2014HIV-1 drug resistance in Kenya14

Limitations Generalizability Transmitted HIVDR: – Inability to determine acute HIV infections – Reported ART exposure Acquired HIVDR: – Cross sectional design, one-off plasma viral load 12/06/2014HIV-1 drug resistance in Kenya15

Summary Conclusions – Low levels of transmitted HIVDR; geographic variations – Viremia and Acquired HIVDR comparable to other settings Recommendations – Continued surveillance for transmitted and acquired HIVDR – Prioritize and strengthen adherence support – Youth friendly ART support and initiatives 12/06/2014HIV-1 drug resistance in Kenya16

Acknowledgement KEMRI/Wellcome Trust Research Programme – James Berkley – Eduard Sanders PASER / University of Amsterdam – Tobias F. Rinke de Wit Health Protection Agency, London – Pat Cane – Antiviral unit Patients and staff at the HIV clinic, Kilifi District Hospital 6/12/2014HIV-1 drug resistance in Kenya17