Prevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4–8 weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011–12 and 2012–13
Abstract Background South Africa (SA) has expanded efforts to reduce mother-to-child transmission of HIV (MTCT) to less than 2% at six weeks after birth and to less than 5% at 18 months postpartum by 2016. Despite improved antiretroviral regimens and coverage between 2001 and 2016, there is little d...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-09-01
|
| Series: | BMC Infectious Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12879-019-4339-y |
| _version_ | 1818922850203992064 |
|---|---|
| author | Gillian M. Hunt Johanna Ledwaba Anna Salimo Monalisa Kalimashe Thu-Ha Dinh Debra Jackson Gayle Sherman Adrian Puren Nobubelo K. Ngandu Carl Lombard Lynn Morris Ameena Goga |
| author_facet | Gillian M. Hunt Johanna Ledwaba Anna Salimo Monalisa Kalimashe Thu-Ha Dinh Debra Jackson Gayle Sherman Adrian Puren Nobubelo K. Ngandu Carl Lombard Lynn Morris Ameena Goga |
| author_sort | Gillian M. Hunt |
| collection | DOAJ |
| description | Abstract Background South Africa (SA) has expanded efforts to reduce mother-to-child transmission of HIV (MTCT) to less than 2% at six weeks after birth and to less than 5% at 18 months postpartum by 2016. Despite improved antiretroviral regimens and coverage between 2001 and 2016, there is little data on infant HIV drug resistance. This paper tracks the prevalence of HIV drug resistance patterns amongst HIV infected infants from three nationally representative studies that assessed the effectiveness of national programs to prevent MTCT (PMTCT). The first study was conducted in 2010 (under the dual therapy PMTCT policy), the second from 2011 to 12 (PMTCT Option A policy) and the third from 2012 to 13 (PMTCT Option A policy). From 2010 to 2013, infant non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure increased from single dose to daily throughout breastfeeding; maternal nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI exposure increased with initiation of NNRTI-and NRTI- containing triple antiretroviral therapy (ART) earlier in gestation and at higher CD4 cell counts. Methods Three nationally representative surveys were conducted in 2010, 2011–12 and 2012–13. During the surveys, mothers with known, unknown, or no exposure to antiretrovirals for PMTCT and their infants were included, and MTCT was measured. For this paper, infant dried blood spots (iDBS) from HIV PCR positive infants aged 4–8 weeks, with consent for additional iDBS testing, were analysed for HIV drug resistance at the National Institute of Communicable Diseases (NICD), SA, using an in-house assay validated by the Centers for Disease Control and Prevention (CDC). Total viral nucleic acid was extracted from 2 spots and amplified by nested PCR to generate a ~ 1 kb amplicon that was sequenced using Sanger sequencing technologies. Sequence assembly and editing was performed using RECall v3. Results Overall, HIV-1 drug resistance was detected in 51% (95% Confidence interval (CI) [45–58%]) of HIV PCR positive infants, 37% (95% CI [28–47%]) in 2010, 64% (95% CI [53–74%]) in 2011 and 63% (95% CI [47–77%]) in 2012 (p < 0.0001), particularly to the NNRTI drug class. Pooled analyses across all three surveys demonstrated that infants whose mothers received ART showed the highest prevalence of resistance (74%); 26% (21/82) of HIV PCR positive infants with no or undocumented antiretroviral drug (ARV) exposure harboured NNRTI resistance. Conclusions These data demonstrate increasing NNRTI resistance amongst newly-diagnosed infants in a high HIV prevalence setting where maternal ART coverage increased across the years, starting earlier in gestation and at higher CD4 cell counts. This is worrying as lifelong maternal ART coverage for HIV positive pregnant and lactating women is increasing. Also of concern is that resistant virus was detected in HIV positive infants whose mothers were not exposed to ARVs, raising questions about circulating resistant virus. Numbers in this group were too small to assess trends over the three years. |
| first_indexed | 2024-12-20T02:00:05Z |
| format | Article |
| id | doaj.art-04cbce4f51e54be2a64cb5fe2419cafd |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-20T02:00:05Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-04cbce4f51e54be2a64cb5fe2419cafd2022-12-21T19:57:21ZengBMCBMC Infectious Diseases1471-23342019-09-0119S11710.1186/s12879-019-4339-yPrevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4–8 weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011–12 and 2012–13Gillian M. Hunt0Johanna Ledwaba1Anna Salimo2Monalisa Kalimashe3Thu-Ha Dinh4Debra Jackson5Gayle Sherman6Adrian Puren7Nobubelo K. Ngandu8Carl Lombard9Lynn Morris10Ameena Goga11Centre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory ServicesCentre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory ServicesCentre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory ServicesCentre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory ServicesUS Centers for Disease Control and Prevention, Center for Global Health, Division of Global HIV/TBSchool of Public Health, University of the Western CapeCentre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory ServicesCentre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory ServicesHealth Systems Research Unit, South African Medical Research CouncilBiostatistics Unit, South African Medical Research CouncilCentre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory ServicesHealth Systems Research Unit, South African Medical Research CouncilAbstract Background South Africa (SA) has expanded efforts to reduce mother-to-child transmission of HIV (MTCT) to less than 2% at six weeks after birth and to less than 5% at 18 months postpartum by 2016. Despite improved antiretroviral regimens and coverage between 2001 and 2016, there is little data on infant HIV drug resistance. This paper tracks the prevalence of HIV drug resistance patterns amongst HIV infected infants from three nationally representative studies that assessed the effectiveness of national programs to prevent MTCT (PMTCT). The first study was conducted in 2010 (under the dual therapy PMTCT policy), the second from 2011 to 12 (PMTCT Option A policy) and the third from 2012 to 13 (PMTCT Option A policy). From 2010 to 2013, infant non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure increased from single dose to daily throughout breastfeeding; maternal nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI exposure increased with initiation of NNRTI-and NRTI- containing triple antiretroviral therapy (ART) earlier in gestation and at higher CD4 cell counts. Methods Three nationally representative surveys were conducted in 2010, 2011–12 and 2012–13. During the surveys, mothers with known, unknown, or no exposure to antiretrovirals for PMTCT and their infants were included, and MTCT was measured. For this paper, infant dried blood spots (iDBS) from HIV PCR positive infants aged 4–8 weeks, with consent for additional iDBS testing, were analysed for HIV drug resistance at the National Institute of Communicable Diseases (NICD), SA, using an in-house assay validated by the Centers for Disease Control and Prevention (CDC). Total viral nucleic acid was extracted from 2 spots and amplified by nested PCR to generate a ~ 1 kb amplicon that was sequenced using Sanger sequencing technologies. Sequence assembly and editing was performed using RECall v3. Results Overall, HIV-1 drug resistance was detected in 51% (95% Confidence interval (CI) [45–58%]) of HIV PCR positive infants, 37% (95% CI [28–47%]) in 2010, 64% (95% CI [53–74%]) in 2011 and 63% (95% CI [47–77%]) in 2012 (p < 0.0001), particularly to the NNRTI drug class. Pooled analyses across all three surveys demonstrated that infants whose mothers received ART showed the highest prevalence of resistance (74%); 26% (21/82) of HIV PCR positive infants with no or undocumented antiretroviral drug (ARV) exposure harboured NNRTI resistance. Conclusions These data demonstrate increasing NNRTI resistance amongst newly-diagnosed infants in a high HIV prevalence setting where maternal ART coverage increased across the years, starting earlier in gestation and at higher CD4 cell counts. This is worrying as lifelong maternal ART coverage for HIV positive pregnant and lactating women is increasing. Also of concern is that resistant virus was detected in HIV positive infants whose mothers were not exposed to ARVs, raising questions about circulating resistant virus. Numbers in this group were too small to assess trends over the three years.http://link.springer.com/article/10.1186/s12879-019-4339-yHIV drug resistance genotypingDried blood spotsChildren |
| spellingShingle | Gillian M. Hunt Johanna Ledwaba Anna Salimo Monalisa Kalimashe Thu-Ha Dinh Debra Jackson Gayle Sherman Adrian Puren Nobubelo K. Ngandu Carl Lombard Lynn Morris Ameena Goga Prevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4–8 weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011–12 and 2012–13 BMC Infectious Diseases HIV drug resistance genotyping Dried blood spots Children |
| title | Prevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4–8 weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011–12 and 2012–13 |
| title_full | Prevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4–8 weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011–12 and 2012–13 |
| title_fullStr | Prevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4–8 weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011–12 and 2012–13 |
| title_full_unstemmed | Prevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4–8 weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011–12 and 2012–13 |
| title_short | Prevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4–8 weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011–12 and 2012–13 |
| title_sort | prevalence of hiv 1 drug resistance amongst newly diagnosed hiv infected infants age 4 8 weeks enrolled in three nationally representative pmtct effectiveness surveys south africa 2010 2011 12 and 2012 13 |
| topic | HIV drug resistance genotyping Dried blood spots Children |
| url | http://link.springer.com/article/10.1186/s12879-019-4339-y |
| work_keys_str_mv | AT gillianmhunt prevalenceofhiv1drugresistanceamongstnewlydiagnosedhivinfectedinfantsage48weeksenrolledinthreenationallyrepresentativepmtcteffectivenesssurveyssouthafrica2010201112and201213 AT johannaledwaba prevalenceofhiv1drugresistanceamongstnewlydiagnosedhivinfectedinfantsage48weeksenrolledinthreenationallyrepresentativepmtcteffectivenesssurveyssouthafrica2010201112and201213 AT annasalimo prevalenceofhiv1drugresistanceamongstnewlydiagnosedhivinfectedinfantsage48weeksenrolledinthreenationallyrepresentativepmtcteffectivenesssurveyssouthafrica2010201112and201213 AT monalisakalimashe prevalenceofhiv1drugresistanceamongstnewlydiagnosedhivinfectedinfantsage48weeksenrolledinthreenationallyrepresentativepmtcteffectivenesssurveyssouthafrica2010201112and201213 AT thuhadinh prevalenceofhiv1drugresistanceamongstnewlydiagnosedhivinfectedinfantsage48weeksenrolledinthreenationallyrepresentativepmtcteffectivenesssurveyssouthafrica2010201112and201213 AT debrajackson prevalenceofhiv1drugresistanceamongstnewlydiagnosedhivinfectedinfantsage48weeksenrolledinthreenationallyrepresentativepmtcteffectivenesssurveyssouthafrica2010201112and201213 AT gaylesherman prevalenceofhiv1drugresistanceamongstnewlydiagnosedhivinfectedinfantsage48weeksenrolledinthreenationallyrepresentativepmtcteffectivenesssurveyssouthafrica2010201112and201213 AT adrianpuren prevalenceofhiv1drugresistanceamongstnewlydiagnosedhivinfectedinfantsage48weeksenrolledinthreenationallyrepresentativepmtcteffectivenesssurveyssouthafrica2010201112and201213 AT nobubelokngandu prevalenceofhiv1drugresistanceamongstnewlydiagnosedhivinfectedinfantsage48weeksenrolledinthreenationallyrepresentativepmtcteffectivenesssurveyssouthafrica2010201112and201213 AT carllombard prevalenceofhiv1drugresistanceamongstnewlydiagnosedhivinfectedinfantsage48weeksenrolledinthreenationallyrepresentativepmtcteffectivenesssurveyssouthafrica2010201112and201213 AT lynnmorris prevalenceofhiv1drugresistanceamongstnewlydiagnosedhivinfectedinfantsage48weeksenrolledinthreenationallyrepresentativepmtcteffectivenesssurveyssouthafrica2010201112and201213 AT ameenagoga prevalenceofhiv1drugresistanceamongstnewlydiagnosedhivinfectedinfantsage48weeksenrolledinthreenationallyrepresentativepmtcteffectivenesssurveyssouthafrica2010201112and201213 |