HIV-1 drug resistance in a rural HIV

clinic in Coastal Kenya.

Amin Hassan

KEMRI/Wellcome Trust Research Programme, Kilifi, Kenya

22nd November 2013

Layout

• Background

• Objective

• Methods

• Results

• Summary

• Acknowledgement

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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– 10000 (2003) to ~500000 (2012); 72% coverage (UNAIDS 2012)

– Reduction in HIV-related morbidity and mortality

– Emergence and transmission of HIVDR11/04/23 HIV-1 drug resistance in Kenya 3

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

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Objective

• To describe HIV-1 transmitted and acquired drug

resistance in a rural HIV clinic in Coastal Kenya.

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Study site

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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

testing11/04/23 HIV-1 drug resistance in Kenya 7

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

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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

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Transmitted HIVDR (N=182)

• Females: 138 (76%)

• Mean age: 35 years

• Transmitted HIVDR: 2/182, 1.1% (95% CI, 0.1 – 3.9)

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Mutation Drug Class Subtype Gender Age (years)

T215D NRTI A1 Female 16.4

M46L PI A1 Female 22.9

Viremia and Acquired HIVDR (N=232)

• Median duration on ART:

14 months (IQR: 10 - 18)

• HIV-1 Viremia:

25% (95% CI: 19 - 31)

• Acquired HIVDR:

13% (95% CI: 9 - 18 )

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Acquired HIVDR mutations (N=29)

4

23

2 2 21 1 1 1

13

86

32 2 2

1 1 1 1

TAM

s

M18

4

D67

K219

T215 L7

4

M41 K7

0

T69

K103

Y181

G19

0

V106

K101

K238

M23

0

Y318

F227

V108

Y188

NRTI mutations NNRTI mutations

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Dual-class resistance, n= 25 (86%)

Correlates of Viremia, Acquired DR (N=232)

Correlate Categories *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 – 34.9

≥ 35.0

Reference

0.3 (0.2 – 0.5)0.002

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*Adjusted for gender, marital status, education status, baseline regimen, drug substitution and duration on ART.

Viremia and Acquired HIVDR by age (N=232)

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Limitations

• Generalizability

• Transmitted HIVDR:

– Inability to determine acute HIV infections

– Reported ART exposure

• Acquired HIVDR:

– Cross sectional design, one-off plasma viral load

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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

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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

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