Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique

Antúnes, Francisco; Zindoga, Pereira; Gómes, Perpétua; Augusto, Orvalho; Mahumane, Isabel; Veloso, L.C.; Valadas, Emília; Camacho, Ricardo Jorge

doi:10.1371/journal.pone.0131994

Cited by 12 publications

(10 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Higher virologic suppression rates have been reported while on second-line PI regimens compared to second-line NNRTI regimens (80% vs. 25%; p=0.009), 19 reflecting the potency of boosted PI regimens and the reduced risk of archived mutations compared to NNRTIs. 20,21 Although the majority of our patients remained virologically suppressed throughout the study period, 27% developed at least one episode of VF during the study monitoring period. We observed that 55% of those with an initial elevated viral load had persistent VF for 24 weeks (two consecutive measurements) and 32% had persistent VF for 48 weeks (three consecutive measurements).…”

Section: Discussionmentioning

confidence: 80%

Treatment Outcomes and Resistance Patterns of Children and Adolescents on Second-Line Antiretroviral Therapy in Asia

Prasitsuebsai

Teeraananchai²,

Singtoroj

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

View full text Add to dashboard Cite

Background Data on pediatric treatment outcomes and drug resistance while on second-line antiretroviral therapy (ART) are needed to guide HIV care in resource-limited countries. Methods HIV-infected children <18 years old who were switched or switching to second-line ART after first-line failure were enrolled from eight sites in Indonesia, Thailand, and Vietnam. Genotyping was performed at virologic failure (VF; HIV-RNA >1000copies/mL). Cox proportional hazards regression was used to evaluate factors predicting VF. Results Of 277 children, 41% were female. At second-line switch, age was 7.5 (5.3–10.3) years, CD4 count was 300 (146–562) cells/mm3 and percentage was 13 (7–20)%; HIV-RNA was 5.0 (4.4–5.5) log10 copies/mL. Second-line regimens contained lamivudine (90%), tenofovir (43%), zidovudine or abacavir (30%), lopinavir (LPV/r; 91%), and atazanavir (ATV; 7%). After 3.3 (1.8–5.3) years on second-line ART, CD4 was 763 (556–1060) cells/mm3 and 26 (20–31)%. VF occurred in 73 (27%), with an incidence of 7.25 per 100 person-years (95% confidence interval [CI] 5.77–9.12). Resistance mutations in 50 of 73 children with available genotyping at first VF included M184V (56%), ≥1 thymidine analogue mutation (TAM; 40%), >4 TAMs (10%), Q151M (4%), any major LPV mutation (8%), >6 LPV mutations (2%), and any major ATV mutation (4%). Associations with VF included age >11 years (hazard ratio [HR] 4.06; 95%CI 2.15–7.66) and HIV-RNA >5.0 log10 copies/mL (HR 2.42; 95%CI 1.27–4.59) at switch, and was seen more commonly in children from Vietnam (HR 2.79; 95%CI 1.55 – 5.02). Conclusions One-fourth of children developed VF while on second-line ART. However, few developed major mutations to protease inhibitors.

show abstract

Section: Discussionmentioning

confidence: 80%

Treatment Outcomes and Resistance Patterns of Children and Adolescents on Second-Line Antiretroviral Therapy in Asia

Prasitsuebsai

Teeraananchai²,

Singtoroj

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

View full text Add to dashboard Cite

show abstract

“…Poor adherence and mutation can lead to drug resistance [16]. Although our study didn’t include sequencing of the genetic material, some studies revealed that NVP had a high rate of resistance to HIV among infants [18, 19].…”

Section: Discussionmentioning

confidence: 99%

Viral suppression rate among children tested for HIV viral load at the Amhara Public Health Institute, Bahir Dar, Ethiopia

et al. 2019

View full text Add to dashboard Cite

Background Human immunodeficiency virus (HIV) infected children represent a very vulnerable population for anti-retroviral therapy (ART) drug resistance. As a global target, 90% of patients receiving ART should have HIV-RNA viral suppression. A threshold of > 1000 RNA copies/ml is used to define non-suppressed viral load. If it is confirmed in the laboratory, adherence should be addressed and should be followed by the switch to second-line ART. Therefore, the aim of this study was to assess the rate of viral load suppression among children tested at the Amhara Public Health Institute (APHI), Bahir Dar. Methods Institutional based cross-sectional study design was conducted from July 01, 2017 to June 30, 2018, in children under the age of 15 years. Socio-demographic, clinical and HIV1RNA viral load data were collected from the excel database. The data were analyzed in SPSS 20.0 statistical software. Results A total of 1567 children, age ranged from one to 14 years, were tested for HIV viral load. Of which, about 54% were males. Children were treated using nevirapine-based (76.7%), efavirenz-based (21.8%) and protease inhibitor-based (1.5%) anti-retroviral drugs. Non-suppressed HIV viral load was found in 28.3% of the participants. High viral load (> 1000 cp/ml) were found in 24% of the children below the age of five years. Children on nevirapine-based treatment had about two times more non-suppressed viral load (Adjusted odds ratio [AOR]: 1.90; 95%CI: 1.41–2.56; P < 0.001) compared to those who had efavirenz-based treatment. However, adherence (P: 0.204) was not associated with non-suppressed viral load. Conclusions There was a high rate of non-suppressed HIV viral load among children tested at APHI. Specifically, the odds of having a non-suppressed viral load was higher in NVP based treatment users. Hence, comprehensive management and follow up of children on ART, and testing for resistance as well as viral load could help to reduce the problem in advance.

show abstract

“…Single-point mutations confer resistance to nevirapine and are known to be selected in almost all exposed even to a single dose of this drug. 25,26 Infants were transitioned to lopinavir/ritonavir at 42 weeks post menstrual age but this drug is known to present significant adherence challenges due to poor palatability. Better formulations of antiretroviral drugs with better tolerability and simplified dosing for this age group is an urgent research priority.…”

Section: Discussionmentioning

confidence: 99%

12-month outcomes of HIV-infected infants identified at birth at one maternity site in Johannesburg, South Africa: an observational cohort study

et al. 2018

View full text Add to dashboard Cite

Summary: Background: Initiation of antiretroviral therapy (ART) following diagnosis at birth is an emerging area of paediatric HIV care. We present outcomes of HIV-infected infants identified at birth at Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa. Methods: From September 2013 (Era 1), only “high risk” HIV-exposed infants were offered diagnostic HIV PCR tests at birth. From June 2014 (Era 2) all HIV-exposed infants were offered laboratory-based diagnostic PCR tests. From October 2014 (Era 3), point-of-care (POC) diagnostic PCR tests were added if staff availability allowed. We describe time to ART initiation, mortality, retention in care and viral suppression among the HIV-infected infants identified across these eras born through June 2016. Findings: Of 5449 HIV-exposed infants tested, 88 confirmed cases of HIV-infection were identified and included in the study; 86 (97·7%) started ART. Age at ART initiation decreased from a median of nine days in Eras 1 and 2 to two days in Era 3. In Era 3, the 35 HIV-infected neonates who were co-tested with POC started ART earlier (82·9% ≤48 hours after birth) than the 29 infants not co-tested (3·5% ≤ 48 hours; median of six days). The probability of mortality by twelve months was 0·14 (95% CI 0·08-0·24) and did not differ by eras. Of the infants who survived and initiated ART at the site, retention at twelve months was 77·8%. Of those infants retained in care, 71·3% had viral load <400 copies/ml at twelve months with no differences between eras. Interpretation: HIV-infected infants can be identified at birth and ART initiated within hours to days. However, reducing mortality and improving retention and viral suppression remain urgent priorities.

show abstract

Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique

Cited by 12 publications

References 36 publications

Treatment Outcomes and Resistance Patterns of Children and Adolescents on Second-Line Antiretroviral Therapy in Asia

Treatment Outcomes and Resistance Patterns of Children and Adolescents on Second-Line Antiretroviral Therapy in Asia

Viral suppression rate among children tested for HIV viral load at the Amhara Public Health Institute, Bahir Dar, Ethiopia

12-month outcomes of HIV-infected infants identified at birth at one maternity site in Johannesburg, South Africa: an observational cohort study

Contact Info

Product

Resources

About