Surveillance of HIV Drug Resistance in Children Receiving Antiretroviral Therapy: A Pilot Study of the World Health Organization’s Generic Protocol in Maputo, Mozambique

Augusto, Orvalho; Bila, Dulce; Macassa, Eugenia; Vubil, Adolfo; Jani, Ilesh; Pillon, Roberto; Sandstrom, Paul; Sutherland, Donald; Giaquinto, Carlo; Jordan, Michael R.; Bertagnolio, Silvia

doi:10.1093/cid/cis006

Cited by 20 publications

(16 citation statements)

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“…In the multivariable logistic model the mothers that took antiretrovirals to prophylaxis their fetus/infant significantly increased risk of NVP resistance (OR = 48.65) among children comparing to mothers who received ART. This finding corroborates the results observed in Maputo by Vaz et al [ 26 ], substantiating the evidence that sd-NVP-based prophylactic regimens lead to a marked increase in the risk of resistance to this ARV and to the subsequent use of NNRTIs [ 3 , 12 , 27 , 28 ].…”

Section: Discussionsupporting

confidence: 91%

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

et al. 2015

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BackgroundSingle-dose nevirapine (sd-NVP) has been the main option for prevention of mother-to-child transmission (PMTCT) of HIV-1 in low-resource settings. However, sd-NVP can induce the selection of HIV-1 resistant mutations in mothers and infants. In Mozambique, there are limited data regarding the profile of NVP resistance associated mutations (RAM) in the context of PMTCT.ObjectivesTo assess the prevalence and the factors associated with NVP RAM among children born to HIV-1 infected mothers enrolled in the PMTCT programme adopted in Mozambique.MethodsOne hundred and fifty seven children aged 6 to 48 weeks were sequentially included (July 2011 to March 2012) at four centres in Maputo. Genotyping of RAM was performed in samples with HIV-1 RNA≥ 100 copies/μL (Viroseq). Sequencing was performed with ABI 3100 (Applied Biosystems). Logistic regression modelling was undertaken to identify the factors associated with NVP RAM.ResultsSeventy-nine children had their samples genotyped. Their median age was 7.0 (3–12) months and 92.4% received prophylaxis with sd-NVP at birth plus daily NVP. 35.4% of mothers received antiretrovirals (ARVs) for PMTCT. ARV RAM were detected in 43 (54.4%) of the children. 45.6% of these children had at least one NVP RAM. The most common mutations associated with NVP resistance were K103N (n = 16) and Y181C (n = 15). NVP RAM was significantly associated with mother exposure to PMTCT (crude odds ratio [OR] 30.3, 95% CI 4.93–186.34) and with mother’s CD4 count < 350 cells/mm3 (crude OR 3.08, 95% CI 1.02–9.32). In the multivariable analysis the mother’s exposure to PMTCT was the only variable significantly associated with NVP RAM (adjusted OR 48.65, 95% CI 9.33–253.66).ConclusionsWe found a high prevalence of NVP RAM among children who were exposed to the drug regimen for PMTCT in Mozambique. The mothers’ exposure to PMTCT significantly increased the risk of NVP RAM.

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Section: Discussionsupporting

confidence: 91%

“…Despite gradually improving access to ART, the proportion of children currently treated in the country is considerably small. As of December 2010 only 23% of HIV-infected children aged < 15 years old in need of ART were receiving this therapy [ 26 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…Even though some studies have shown that age is a risk factor for treatment failure [ 36 – 39 ] and drug resistance [ 40 , 41 ], most likely due to developing metabolic pathways, variable pharmacokinetics and lack of adequate paediatric dosing information, the CHER study did not support this association [ 42 ]. While children who developed major PI mutations in our study were younger at the time of ART initiation than those who did not develop mutations, this difference was not statistically significant.…”

Section: Discussionmentioning

confidence: 99%

Factors Associated with the Development of Drug Resistance Mutations in HIV-1 Infected Children Failing Protease Inhibitor-Based Antiretroviral Therapy in South Africa

et al. 2015

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ObjectiveLimited data are available from the developing world on antiretroviral drug resistance in HIV-1 infected children failing protease inhibitor-based antiretroviral therapy, especially in the context of a high tuberculosis burden. We describe the proportion of children with drug resistance mutations after failed protease inhibitor-based antiretroviral therapy as well as associated factors.MethodsData from children initiated on protease inhibitor-based antiretroviral therapy with subsequent virological failure referred for genotypic drug resistance testing between 2008 and 2012 were retrospectively analysed. Frequencies of drug resistance mutations were determined and associations with these mutations identified through logistic regression analysis.ResultsThe study included 65 young children (median age 16.8 months [IQR 7.8; 23.3]) with mostly advanced clinical disease (88.5% WHO stage 3 or 4 disease), severe malnutrition (median weight-for-age Z-score -2.4 [IQR -3.7;-1.5]; median height-for-age Z-score -3.1 [IQR -4.3;-2.4]), high baseline HIV viral load (median 6.04 log10, IQR 5.34;6.47) and frequent tuberculosis co-infection (66%) at antiretroviral therapy initiation. Major protease inhibitor mutations were found in 49% of children and associated with low weight-for-age and height-for-age (p = 0.039; p = 0.05); longer duration of protease inhibitor regimens and virological failure (p = 0.001; p = 0.005); unsuppressed HIV viral load at 12 months of antiretroviral therapy (p = 0.001); tuberculosis treatment at antiretroviral therapy initiation (p = 0.048) and use of ritonavir as single protease inhibitor (p = 0.038). On multivariate analysis, cumulative months on protease inhibitor regimens and use of ritonavir as single protease inhibitor remained significant (p = 0.008; p = 0.033).ConclusionMajor protease inhibitor resistance mutations were common in this study of HIV-1-infected children, with the timing of tuberculosis treatment and subsequent protease inhibitor dosing strategy proving to be important associated factors. There is an urgent need for safe, effective, and practicable HIV/tuberculosis co-treatment in young children and the optimal timing of treatment, optimal dosing of antiretroviral therapy, and alternative tuberculosis treatment strategies should be urgently addressed.

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“…[73] , [78] , [146] , [148] , [153] , [171] – [173] Co-infections prevalent in the tropics and food shortages are recurring challenges that are far less prevalent in higher income nations. [174] – [177] Drug resistance has not been studied widely in Mozambique [178] .…”

Section: Discussionmentioning

confidence: 99%

Poor Clinical Outcomes for HIV Infected Children on Antiretroviral Therapy in Rural Mozambique: Need for Program Quality Improvement and Community Engagement

et al. 2014

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IntroductionResidents of Zambézia Province, Mozambique live from rural subsistence farming and fishing. The 2009 provincial HIV prevalence for adults 15–49 years was 12.6%, higher among women (15.3%) than men (8.9%). We reviewed clinical data to assess outcomes for HIV-infected children on combination antiretroviral therapy (cART) in a highly resource-limited setting.MethodsWe studied rates of 2-year mortality and loss to follow-up (LTFU) for children <15 years of age initiating cART between June 2006–July 2011 in 10 rural districts. National guidelines define LTFU as >60 days following last-scheduled medication pickup. Kaplan-Meier estimates to compute mortality assumed non-informative censoring. Cumulative LTFU incidence calculations treated death as a competing risk.ResultsOf 753 children, 29.0% (95% CI: 24.5, 33.2) were confirmed dead by 2 years and 39.0% (95% CI: 34.8, 42.9) were LTFU with unknown clinical outcomes. The cohort mortality rate was 8.4% (95% CI: 6.3, 10.4) after 90 days on cART and 19.2% (95% CI: 16.0, 22.3) after 365 days. Higher hemoglobin at cART initiation was associated with being alive and on cART at 2 years (alive: 9.3 g/dL vs. dead or LTFU: 8.3–8.4 g/dL, p<0.01). Cotrimoxazole use within 90 days of ART initiation was associated with improved 2-year outcomes Treatment was initiated late (WHO stage III/IV) among 48% of the children with WHO stage recorded in their records. Marked heterogeneity in outcomes by district was noted (p<0.001).ConclusionsWe found poor clinical and programmatic outcomes among children taking cART in rural Mozambique. Expanded testing, early infant diagnosis, counseling/support services, case finding, and outreach are insufficiently implemented. Our quality improvement efforts seek to better link pregnancy and HIV services, expand coverage and timeliness of infant diagnosis and treatment, and increase follow-up and adherence.

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Surveillance of HIV Drug Resistance in Children Receiving Antiretroviral Therapy: A Pilot Study of the World Health Organization’s Generic Protocol in Maputo, Mozambique

Cited by 20 publications

References 27 publications

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

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

Factors Associated with the Development of Drug Resistance Mutations in HIV-1 Infected Children Failing Protease Inhibitor-Based Antiretroviral Therapy in South Africa

Poor Clinical Outcomes for HIV Infected Children on Antiretroviral Therapy in Rural Mozambique: Need for Program Quality Improvement and Community Engagement

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