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Still Far From 90-90-90

Virologic Outcomes of Children on Antiretroviral Therapy in Nurse-led Clinics in Rural Lesotho

Puga, Daniel MD*; Cerutti, Bernard PhD, MPH; Molisana, Cheleboi MLT; Bader, Joëlle MSc§; Faturiyele, Olatunbosun MD*; Ringera, Isaac RN*; Lejone, Thabo RN*; Pfeiffer, Karolin MD, MPH; Klimkait, Thomas PhD§; Labhardt, Niklaus D. MD, MIH‖**

Author Information
The Pediatric Infectious Disease Journal: January 2016 - Volume 35 - Issue 1 - p 78-80
doi: 10.1097/INF.0000000000000929

Abstract

The third target of the Joint United Nations Programme on HIV and AIDS (UNAIDS) 90-90-90 strategy to end the HIV/AIDS epidemic is to achieve 90% viral suppression among those patients enrolled on combined antiretroviral therapy (cART) by 2020.1 The World Health Organization (WHO) recommended routine viral load (VL) monitoring for all patients on cART, which is a critical step to achieve this target.2 However, because of high current cost, scaling up VL monitoring is slow in resource-limited high-HIV prevalence settings, and data on the virologic outcome specifically for children on cART in sub-Saharan Africa remain scarce. Only few studies are available, and they all derive from either tertiary hospitals or clinics specialized in pediatric HIV care.3–6 To our knowledge up to now, no study has specifically described virologic outcomes for children on cART at remote nurse-led clinics in Africa. In this report, we evaluated viral suppression in HIV-infected children on cART and factors associated with failure to suppress in a cross-sectional study conducted in the real-life context of 10 rural nurse-led facilities in Lesotho, Southern Africa.

MATERIALS AND METHODS

Data for this study were derived from a registered cross-sectional survey on virologic suppression and chronic comorbidities among adults and children on cART, conducted in May and June 2014 in 2 district hospitals and 8 health centers in the districts Thaba-Tseka and Butha-Buthe (www.clinicaltrials.gov; NCT02126696). All 10 sites involved in this study provide nurse-led cART. In this report, we cover the findings related to virologic suppression among children. Data from adults were reported separately.7

The estimated adult HIV prevalence in Lesotho for 2012 is 22.9%. UNAIDS estimates that approximately 36,000 children aged 0–14 years in Lesotho are infected with HIV, and only 15% of them were receiving cART in 2012.8 Lesotho’s antiretroviral therapy program is decentralized, and the task of HIV care was shifted to nurses at hospitals and health centers.

HIV-infected children who attended the clinics between May 5, 2014, and June 17, 2014, were screened for enrollment. Inclusion criteria were age <16 years and first-line cART for ≥6 months. Before enrollment, caregivers of children provided individual oral and written informed consent. Ethics approval was received by the National Health Research and Ethics Committee of Lesotho (ID 01-2014) and the “Ethikkomission Nordwest- und Zentralschweiz” in Switzerland (ID 2014–029).

Social and biomedical characteristics were collected and recorded, and a structured patient and caregiver interview was conducted. Blood samples were centrifuged, and plasma was frozen in place and stored at −20°C. Aliquots were subsequently shipped on dry ice to a reference laboratory in Switzerland for analysis. Viral RNA was prepared using an automated extractor (Nuclisens Easymag, Biomerieux, Switzerland) and quantified using a quantitative, validated protocol.9 Virologic success was defined as VL <80 copies/mL. Children with unsuppressed VL in the study were managed according to the National Guidelines of Lesotho.10 Potential social and biomedical predictors of virologic success were evaluated by univariate logistic regression modeling. Predictors with a significance level <0.15 were subsequently included in a multivariate logistic regression model. Analyses were run on R 2.14.2 (R Foundation for Statistical Computing, Vienna, Austria) and TIBCO Spotfire S+® 8.2 for Windows (TIBCO Software Inc, Palo Alto, CA).

RESULTS

During the study period, 240 children attended cART consultations at the 10 sites. Forty-four (18.3%) were excluded (28 had no caregiver to provide consent, 11 were on cART for <6 months and 5 were on second-line cART). Among the 196 included in the study, 5 (2.6%) had to be excluded because of blood samples of insufficient quality. Of the 191 children included in the analysis, the median age of cART initiation was 5.8 years (interquartile range: 2.3–8.6 years), and the median age of children at the time of the study was 9.8 years (6.8–12.7 years). Their characteristics are displayed in Table 1 and Table, Supplemental Digital Content 1, https://links.lww.com/INF/C282.

T1-16
TABLE 1:
Description of Children Included in the Study, Rates of Virologic Success and Unadjusted and Adjusted ORs of Patients’ Characteristics for Virologic Success

The overall virologic success rate was 72.3% (95% confidence interval: 65.8%–78.7%). In the univariate analysis, the following variables showed some evidence of association with poor virologic suppression in children (see Table 1): poor adherence (self-reported, visual analogue scale of <95%), history of treatment interruption ≥2 days, nevirapine-based cART (compared with efavirenz), WHO stage I and II before cART initiation and nonorphan status. In the subsequently conducted multivariate model, only nevirapine-based cART (compared with efavirenz) was predictive for poor virologic suppression.

The full listing of all characteristics tested for association with virologic success is given in Table, Supplemental Digital Content 1, https://links.lww.com/INF/C282. The following variables showed no significant association: type of facility, age at cART start, gender, immunological stage and hemoglobin at baseline, household wealth quintile, travel time and travel mode to the facility, disclosure of HIV status, pill count–assessed adherence, time on antiretroviral therapy, weight, height and body mass index for age at study visit, and hemoglobin at study visit (Table, Supplemental Digital Content 1, https://links.lww.com/INF/C282).

DISCUSSION

This cross-sectional survey in remote, nurse-led clinics in rural Lesotho found a viral suppression rate of 72% among pediatric patients on first-line cART. Apart from nevirapine-based cART, no other variables predicted nonsuppression. Although the viral suppression rate in our study was not inferior to those achieved by specialized care at tertiary hospitals in South Africa,6 more than one quarter of the children presented with unsuppressed VL. Thus, observed virologic outcomes fall short of the UNAIDS target of 90% suppression.

This study was conducted on confirmed HIV-infected children who had continuous access to cART and who could be retained in care for at least 6 months; therefore, generalizing the findings of this study should be restricted to similar populations. Moreover, as a note of caution, this study may have been underpowered for detecting smaller associations between assessed predictors and virologic outcome.

The only patient characteristic found to be associated with poor virologic outcome in our study was nevirapine-based cART compared with efavirenz. Similar results have been observed before for adults and children, which is in support of the WHO recommendations to preferably initiate pediatric patients on nonnevirapine-based antiretroviral regimens.2,11,12

All other clinical or sociodemographic characteristics collected in our study failed to predict virologic outcome, including those described as predictors in other publications, such as duration on cART, adherence measured by pill count and household wealth (see Table, Supplemental Digital Content 1, https://links.lww.com/INF/C282). Nearly all virological failures would have been missed by monitoring methods other than VL, implying that routine VL monitoring is the only means to reliably assess virologic outcome. In settings where VL monitoring is routine, pediatric virologic suppression rates of up to 92% have been reached.13

In conclusion, our findings endorse the 2013 WHO recommendation to scale up VL monitoring in resource limited, high-prevalence settings as a critical step to achieve the goal of ≥90% suppression rate by 2020.

ACKNOWLEDGMENTS

The authors thank the children and their caregivers for their participation in the study.

REFERENCES

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        Keywords:

        viral load; virologic outcomes; pediatric; children; Africa; HIV; antiretroviral therapy

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