TRANSMITTED HIV DRUG RESISTANCE SURVEY IN TWO PROVINCES IN PAPUA NEW GUINEAEvelyn Lavu1, Nick Dala2, Anup Gurung3, Ellan Kave1, Euodia Mosoro1, Jessica Markby4, Eman Aleksic4, Janet Gare4,5, Imogen Elsum2, Gideon Nano6, Mark Myatt7, Petronia Kaima8, Suzanne Crowe4, Silvia Bertagnolio9, Anna Hearps4*, Michael R. Jordan10*

1Central Public Health Laboratory, Port Moresby, Papua New Guinea (PNG), 2National Department of Health, Port Moresby, PNG, 3WHO, Port Moresby, PNG, 4Burnet Institute, Melbourne, Australia, 5Institute for Medical Research, Goroka, PNG, 6Port Moresby, PNG, 7Brixton Health, Wales, United Kingdom, 8Mt Hagen Hospital, PNG, 9HIV Department, WHO, Geneva, Switzerland, 10Tufts University School of Medicine, Boston, USA *Denotes co-senior authorship

Survey design:

• Surveillance of transmitted HIV drug resistance (TDR) in individuals recently infected with HIV was performed following WHO-suggested methods in two regions between May 2013-April 2014

Recruitment areas:

Genotyping methods:

Recruitment criteria:

Data analysis:

BACKGROUND

METHODS

• Papua New Guinea (PNG) is a pacific island nation of 7.3 million people and has an estimated HIV prevalence of 0.65%

• The HIV epidemic in PNG is predominantly heterosexual, with females representing approximately 62% of HIV cases

• Females are diagnosed with HIV at a younger age than males

• 20% of HIV-infected women are aged 15-24 years

• Antiretroviral therapy (ART) became available in PNG in 2004; 80.3 % of people in need were receiving it as of 2015

• Clinical monitoring of HIV-infected individuals is limited in PNG, with inconsistent availability of CD4+ T cell testing

• Viral load and HIV drug resistance testing are not routinely available

• First-line ART in PNG consists of the nucleoside reverse transcriptase inhibitors (NRTIs) Zidovudine or Tenofovir + Lamivudine and one of the non-nucleoside reverse transcriptase inhibitors (NNRTIs) Efavirenz or Nevirapine

• Protease inhibitors (PI) are used as second-line drugs

• The prevalence of transmitted HIV drug resistance (TDR) in recently infected antiretroviral drug naïve individuals in PNG has not been fully characterised

• Port Moresby, National Capital District

• Heduru HIV/STI clinic

• Anglicare Clinic

• Mt Hagen, Western Highlands Province

• Tininga Clinic, Mt Hagen Hospital

• Rebiamul Hospital VCT centre

• Dried Blood Spots (DBS) prepared from venous blood

• Drug resistance detected using an in-house genotyping assay

• Testing performed at the WHO-designated HIV Drug Resistance Laboratory at the Burnet Institute (Melbourne, Australia)

• HIV+ , ART naïve, Aged ≤30

• First pregnancy or never pregnant , if female

• Resistance mutations were defined using the WHO 2009 SDRM list

• Point prevalence with 95% CI were calculated

• Classification of TDR prevalence

• To analyse all available specimens rather than N≤47 per the WHO TDR survey method (Bennett and Myatt, AVT 2007); Lot Quality Assurance sampling with floor and ceiling decision rules modelled to return probabilities of classification similar to those of the original method were used (adapted from Myatt M, FHI 360/FANTA-III, 2012)

CONCLUSIONS

RESULTS

• NNRTI drug resistance (16.1%) in ARV drug naïve individuals in Port Moresby is amongst the highest reported globally to date

• Observed levels of TDR threaten to limit the on-going effective use of NNRTIs as a component of first-line ART

• NNRTI resistance is less common in Mt Hagen but is detected with a point prevalence of 8.2%

• Improved monitoring and correction of ART programme factors associated with emergence and transmission of drug resistant HIV is essential

• Nationally representative surveillance of HIVDR among first-line ART initiators should be urgently implemented to support choice of nationally recommended first-line ART

Figure 1: Map of PNG showing location of survey sites

Poster number: MOPED723

Mount Hagen

Port Moresby

• 70 individuals were recruited from each region

• The number of specimens successfully genotyped was:

• 62/70 (88.6%) for Port Moresby

• 61/70 (87.1%) for Mt Hagen

• Demographic details of participants with successfully genotyped specimens are shown in Table 1

• Consistent with previous publications, the median age of female participants was younger than males

• 22.0 years for females vs. 27.0 years for males, (Table 1)

Survey population

• Drug resistance mutations were detected in 11/62 individuals (Table 2 and Figure 2)

• NNRTI resistance mutations detected in 10 individuals

• Point prevalence = 16.1% (95% CI 9.0%-27.2%)

• NRTI resistance mutations detected in 2 individuals

• Point prevalence = 3.2% (0.08%-11.0%)

• No PI resistance mutations were detected

• Resistance classification:

• NNRTI resistance: Moderate

• NRTI resistance: Low

• PI resistance: Low

• Drug resistance mutations detected in 5/61 individuals (Table 3 and Figure 3)

• NNRTI resistance mutations detected in 5 individuals

• Point prevalence = 8.2% (95% CI 3.5%-17.8%)

• NRTI resistance mutations detected in 2 individuals

• Point prevalence = 3.2% (0.09%-11.0%)

• No PI resistance mutations were detected

• Resistance classification:

• NNRTI resistance: Low

• NRTI resistance: Low

• PI resistance: Low

Drug resistance levels - Port Moresby Drug resistance levels - Mt Hagen

Table 1: Demographic details of survey population*Port Moresby Mt Hagen Combined cohort

Sample number 62 61 123

Female, n (%) 31 (50%) 41( 67%) 72 (58.5%)

Age, median (IQR)

Entire cohort 25.0 (21.0-28.0) 25.0 (21.0-28.0) 25.0 (21.0-28.0)

Females 22.0 (20.0-28.0) 22.0 (20.0-27.5) 22.0 (20.0-26.0)

Males 27.5 (22.5-29.8) 27.5 (22.5-29.8) 27.0 (23.0-29.0)

Table 2: Drug resistence mutations detected - Port MoresbyPort Moresby Mt Hagen

1 K103N

2 M41L, T215Y K103N

3 G190A

4 K103N, V106MV

5 Y181IV

6 K70E

7 K103N

8 Y181C

9 Y181CY

10 K101E, G190A

11 V106IV, Y181CY, Y188CY

Table 3: Drug resistence mutations detected - Mt HagenPatient NRTI SDRM NNRTI SDRM

1 K219KN Y181C, G190A

2 K103N

3 G190A

4 D67N, K70E, M184V Y181C,G190A

5 Y181CY

#Only includes specimens which were successfully genotyped and passed quality assurance

SDRM = Surveillance drug resistance mutations (2009 list)

Figure 2: Neighbour-joining tree of sequences from Port Moresby Sequences with one of more NNRTI SDRM denoted by red squares and sequences with one or more NNRTI and NRTI SDRM are denoted by yellow squares. WHO reference sequences also included

Figure 3: Neighbour-joining tree of sequences from Mt Hagen Sequences with one of more NNRTI SDRM denoted by red squares and sequences with one or more NNRTI and NRTI SDRM are denoted by yellow squares. WHO references sequences also include

DR00

39

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0063

DR0

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DR01

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0050

DR01

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0119

DR0041

DR0079

DR0002

DR0117

DR0092

DR0099

DR0026

DR0122

DR0040

DR0114

DR0111

DR0065DR0066

DR0124DR0008DR0091DR0042

DR0022DR0055

DR0118

DR0020DR0064DR0125

DR0080

DR0087

DR0069

DR0105

DR0096

DR

0030

DR0088

DR

0089D

R0084DR0090DR00127DR

0107DR

0130

DR0053

DR0094

DR0081DR0073DR0104

DR0077DR0035DR0047DR0086

DR0060

DR0103DR0095

DR0129

DR0052

DR0093

DR0074

DR0003

DR0004

AF067155 IN C

U88824 UG D

AF193276 RU 03 AB

K03455 FR B

DR0062AF005494 BR F1

AB253429 UG A1U54771 TH 01 AE

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WHP0072

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WHP0005WHP0064WHP0080WHP0021

WHP0079WHP0034

WHP0046WHP0032

WHP0028WHP0001

WHP0044

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WHP0077WHP0024WHP0015WHP0078AF067155 IN CWHP0027

WHP0068WHP0010

WHP0063

WHP0083

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WHP0081

WHP0003

WHP0029

WHP0041

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