High Rates of Drug Resistance Among Newly Diagnosed HIV-infected Children in the National Prevention of Mother-to-child Transmission Program in Togo

Salou, Mounérou; Butel, Christelle; Konou, Abla A.; Ekouévi, Didier K.; Vidal, Nicole; Dossim, Sika; Lawson-Evi, K.; Nyasenu, Yawo Tufa; Singo-Tokofaï, Assétina; D’almeida, S.; Tchama, Raissa; Delaporte, Eric; Prince-David, Mireille; Peeters, Martine; Dagnra, Anoumou

doi:10.1097/inf.0000000000001203

Cited by 17 publications

(11 citation statements)

References 28 publications

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“…The prevalence of NVP-associated mutations in our cohort is within the range of previous studies involving children who had been exposed to single-dose or extended-NVP prophylaxis, 27% [13] to 60% [3,14,15]. However, previous studies of single-dose NVP involved younger children and demonstrated that resistance decayed to clinically insignificant levels in most infants by 12 months [2,3,9–11].…”

Section: Discussionsupporting

confidence: 70%

Persistence of HIV drug resistance among South African children given nevirapine to prevent mother-to-child-transmission

Kanthula

Rossouw

Feucht

et al. 2017

Aids

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Objectives We set out to examine the prevalence and persistence of mutations conferring high-level nonnucleoside reverse transcriptase (NNRTI)-resistance in a cohort of HIV-infected children who had failed prophylaxis to prevent mother-to-child-transmission (PMTCT). Design A prospective observational cohort study at the Pediatric HIV Clinic at Kalafong Provincial Tertiary Hospital in Pretoria, South Africa. Methods Children referred for initiation of antiretroviral therapy (ART) were enrolled from July 2010 through February 2013. HIV drug resistance testing was performed using the oligonucleotide ligation assay (OLA) on dried blood spots (DBS) collected at enrolment and monthly follow-up visits for 2 years. Results South African children who failed HIV-prophylaxis had a high prevalence of NNRTI-resistant HIV (46/88; 52%). Among children with NNRTI-resistance, the frequency of the predominant resistant variant in each child’s HIV-quasispecies was high (median 96%) at study entry (median age 7.5 months), and in 26 out of 27 followed a median of 13 months persisted at a high frequency (median 89%). Conclusion Our finding that infants who fail HIV-prophylaxis frequently have long-lived NNRTI-resistant HIV suggests that resistance will likely persist through 36 months of age, when children qualify for NNRTI-based ART. These children may benefit from HIV drug resistance testing to guide selection of their treatment.

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Section: Discussionsupporting

confidence: 70%

Persistence of HIV drug resistance among South African children given nevirapine to prevent mother-to-child-transmission

Kanthula

Rossouw

Feucht

et al. 2017

Aids

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“…The pattern of DRMs found in this study is consistent with the reports from several studies conducted in Africa [ 6 , 8 , 9 ]. The impact of DRMs acquired via PMTCT could not be evaluated in this study, but we previously reported that independent of perinatal antiretroviral (ARV) exposure, 60% of infants diagnosed with perinatal HIV infection in 2012 and 2013 were infected with drug-resistant strains [ 18 ]. Moreover, rates of drug resistance reached 80% in children receiving breast milk from mothers on ART [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

“…The impact of DRMs acquired via PMTCT could not be evaluated in this study, but we previously reported that independent of perinatal antiretroviral (ARV) exposure, 60% of infants diagnosed with perinatal HIV infection in 2012 and 2013 were infected with drug-resistant strains [ 18 ]. Moreover, rates of drug resistance reached 80% in children receiving breast milk from mothers on ART [ 18 ]. These observations support the use of lopinavir-based first-line regimens in children as recommended by the WHO [ 21 ], especially with the recent national recommendations to implement lifelong ART for mothers.…”

Section: Resultsmentioning

confidence: 99%

“…ART has also been scaled up among children, but only 2800 (23.3%) of the 12,000 children (<14 years) infected with HIV in Togo were receiving ART in 2013 [ 16 ]. We previously observed high levels of VF and drug resistance in adults on long-term first-line ART and among newly diagnosed infants (<18 months) [ 17 , 18 ]. The primary objective of this study was thus to determine virological outcome in perinatally HIV-1-infected children and adolescents receiving ART according to the national guidelines and attending routine HIV care centres in Togo.…”

Section: Introductionmentioning

confidence: 99%

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High rates of virological failure and drug resistance in perinatally HIV‐1‐infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo

Salou

Dagnra

Butel

et al. 2016

Journal of the International AIDS Society

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IntroductionAntiretroviral treatment (ART) has been scaled up over the last decade but compared to adults, children living with HIV are less likely to receive ART. Moreover, children and adolescents are more vulnerable than adults to virological failure (VF) and emergence of drug resistance. In this study we determined virological outcome in perinatally HIV-1-infected children and adolescents receiving ART in Togo.MethodsHIV viral load (VL) testing was consecutively proposed to all children and adolescents who were on ART for at least 12 months when attending HIV healthcare services for their routine follow-up visit (June to September 2014). Plasma HIV-1 VL was measured using the m2000 RealTime HIV-1 assay (Abbott Molecular, Des Plaines, IL, USA). Genotypic drug resistance was done for all samples with VL>1000 copies/ml.Results and discussionAmong 283 perinatally HIV-1-infected children and adolescents included, 167 (59%) were adolescents and 116 (41%) were children. The median duration on ART was 48 months (interquartile range: 28 to 68 months). For 228 (80.6%), the current ART combination consisted of two nucleoside reverse transcriptase inhibitors (NRTIs) (zidovudine and lamivudine) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) (nevirapine or efavirenz). Only 28 (9.9%) were on a protease inhibitor (PI)-based regimen. VL was below the detection limit (i.e. 40 copies/ml) for 102 (36%), between 40 and 1000 copies/ml for 35 (12.4%) and above 1000 copies/ml for 146 (51.6%). Genotypic drug-resistance testing was successful for 125/146 (85.6%); 110/125 (88.0%) were resistant to both NRTIs and NNRTIs, 1/125 (0.8%) to NRTIs only, 4/125 (3.2%) to NNRTIs only and three harboured viruses resistant to reverse transcriptase and PIs. Overall, 86% (108/125) of children and adolescents experiencing VF and successfully genotyped, corresponding thus to at least 38% of the study population, had either no effective ART or had only a single effective drug in their current ART regimen.ConclusionsOur study provided important information on virological outcome on lifelong ART in perinatally HIV-1-infected children and adolescents who were still on ART and continued to attend antiretroviral (ARV) clinics for follow-up visits. Actual conditions for scaling up and monitoring lifelong ART in children in resource-limited countries can have dramatic long-term outcomes and illustrate that paediatric ART receives inadequate attention.

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“…The mass scale-up of prevention of mother-to-child transmission services, from Option B to Option B+ is the major success story of the HIV response, but as less children are born with HIV, there is the risk that drug resistance will increase in the fewer children that do become HIV-positive. 53 The WHO estimates that one out of two children newly diagnosed with HIV has a virus resistant to either efavirenz or nevirapine.54…”

Section: Hivdr In the Context Of Pmtct Scale-upmentioning

confidence: 99%

HIV Drug Resistance

2016

Frontiers in HIV Research

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HIV drug resistance KEY POINTS As 'Treat All' is rolled-out worldwide, the emergence of drug-resistant HIV has the potential to become a major public health threat, as it limits treatment options for people living with HIV. Global prevalence of HIV drug resistance (HIVDR) is rising, mainly due to resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs-which make up the backbone of World Health Organization (WHO) first-line antiretroviral treatment regimes. 2018 WHO interim antiretroviral treatment guidelines now recommend dolutegravircontaining regimes as the preferred first-line treatment because of effectiveness and its high barrier to resistance. Weak health systems and low levels of adherence drive HIVDR-particularly in low-and middle-income countries. Increasing access to viral load testing, and monitoring of other clinical factors relating to patient care, patient behaviour, and clinic and programme management can mitigate the rise of HIVDR. Explore this page to find out more about what drug resistance is, how it affects treatment options, drug resistance as a public health threat, the prevalence of HIVDR, responding to HIVDR, and what the future holds. Antiretroviral treatment (ART) is one of the most effective tools in our arsenal of interventions to fight HIV-keeping people healthy and reducing the risk of onward transmission.

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High Rates of Drug Resistance Among Newly Diagnosed HIV-infected Children in the National Prevention of Mother-to-child Transmission Program in Togo

Abstract: Scale-up and improvement of PMTCT strategies resulted in a global decrease of pediatric HIV infections, but our study shows high rates of drug resistance in infants for whom prevention failed.

Cited by 17 publications

References 28 publications

Persistence of HIV drug resistance among South African children given nevirapine to prevent mother-to-child-transmission

Persistence of HIV drug resistance among South African children given nevirapine to prevent mother-to-child-transmission

High rates of virological failure and drug resistance in perinatally HIV‐1‐infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo

HIV Drug Resistance

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