TRANSMITTED HIV DRUG RESISTANCE SURVEY IN TWO … · used (adapted from Myatt M, FHI 360/FANTA-III,...
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TRANSMITTED HIV DRUG RESISTANCE SURVEY IN TWO PROVINCES IN PAPUA NEW GUINEA Evelyn Lavu 1 , Nick Dala 2 , Anup Gurung 3 , Ellan Kave 1 , Euodia Mosoro 1 , Jessica Markby 4 , Eman Aleksic 4 , Janet Gare 4,5 , Imogen Elsum 2 , Gideon Nano 6 , Mark Myatt 7 , Petronia Kaima 8 , Suzanne Crowe 4 , Silvia Bertagnolio 9 , Anna Hearps 4* , Michael R. Jordan 10* 1 Central Public Health Laboratory, Port Moresby, Papua New Guinea (PNG), 2 National Department of Health, Port Moresby, PNG, 3 WHO, Port Moresby, PNG, 4 Burnet Institute, Melbourne, Australia, 5 Institute for Medical Research, Goroka, PNG, 6 Port Moresby, PNG, 7 Brixton Health, Wales, United Kingdom, 8 Mt Hagen Hospital, PNG, 9 HIV Department, WHO, Geneva, Switzerland, 10 Tufts 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 Moresby Port 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 Hagen Patient 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 DR0039 DR0063 DR0061 DR0109 DR0050 DR0100 DR0119 DR0041 DR0079 DR0002 DR0117 DR0092 DR0099 DR0026 DR0122 DR0040 DR0114 DR0111 DR0065 DR0066 DR0124 DR0008 DR0091 DR0042 DR0022 DR0055 DR0118 DR0020 DR0064 DR0125 DR0080 DR0087 DR0069 DR0105 DR0096 DR0030 DR0088 DR0089 DR0084 DR0090 DR00127 DR0107 DR0130 DR0053 DR0094 DR0081 DR0073 DR0104 DR0077 DR0035 DR0047 DR0086 DR0060 DR0103 DR0095 DR0129 DR0052 DR0093 DR0074 DR0003 DR0004 AF067155 IN C U88824 UG D AF193276 RU 03 AB K03455 FR B DR0062 AF005494 BR F1 AB253429 UG A1 U54771 TH 01 AE 10 WHP0004 WHP0050 WHP0065 WHP0067 WHP0045 WHP0059 WHP0009 WHP0031 WHP0013 WHP0018 WHP0057 WHP0030 WHP0048 WHP0007 WHP0022 WHP0066 WHP0072 WHP0042 WHP0005 WHP0064 WHP0080 WHP0021 WHP0079 WHP0034 WHP0046 WHP0032 WHP0028 WHP0001 WHP0044 WHP0076 WHP0020 WHP0033 WHP0069 WHP0036 WHP0039 WHP0074 WHP0052 WHP0062 WHP0053 WHP0060 WHP0006 WHP0025 WHP0071 WHP0073 WHP0023 WHP0077 WHP0024 WHP0015 WHP0078 AF067155 IN C WHP0027 WHP0068 WHP0010 WHP0063 WHP0083 WHP0055 WHP0081 WHP0003 WHP0029 WHP0041 WHP0047 WHP0075 AY371158 CM F2 K03455 FR B U88824 UG D GU201516 CM A2 U54771 TH 01 AE AB253429 UG A1 10
Transcript of TRANSMITTED HIV DRUG RESISTANCE SURVEY IN TWO … · used (adapted from Myatt M, FHI 360/FANTA-III,...
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
DR
0063
DR0
061
DR01
09DR
0050
DR01
00DR
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
10 WH
P00
04
WH
P005
0W
HP0
065
WH
P006
7W
HP0
045
WHP
0059
WHP
0009
WHP0
031
WHP00
13
WHP0018
WHP0057
WHP0030
WHP0048
WHP0007
WHP0022
WHP0066
WHP0072
WHP0042
WHP0005WHP0064WHP0080WHP0021
WHP0079WHP0034
WHP0046WHP0032
WHP0028WHP0001
WHP0044
WHP0076W
HP0020
WH
P0033
WH
P0069
WH
P0036
WH
P0039
WH
P007
4
WH
P005
2
WH
P006
2
WH
P005
3
WH
P006
0
WH
P000
6
WHP
0025
WHP
0071
WHP0
073WHP00
23
WHP0077WHP0024WHP0015WHP0078AF067155 IN CWHP0027
WHP0068WHP0010
WHP0063
WHP0083
WHP0055
WHP0081
WHP0003
WHP0029
WHP0041
WHP0047
WHP0075
AY371158 CM F2
K03455 FR B
U88824 UG DG
U201516 CM A2
U54771 TH 01 AE AB253429 UG
A1
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