Increase in Body Mass Index in Children With HIV, Switched to Tenofovir Alafenamide Fumarate or Dolutegravir Containing Antiretroviral Regimens

Abstract

To the Editors: Recent data indicate excessive weight gain in treatment-naive adults with HIV commenced on antiretroviral therapy (ART) regimens containing tenofovir alafenamide (TAF) or the integrase strand transfer inhibitors (INSTIs) dolutegravir (DTG) and bictegravir.1 Similar trends have been observed in cohorts of virally suppressed HIV-infected adults following switch to TAF or INSTI containing regimens.2,3 It is unclear whether this observation also applies to children with HIV; to date, there are no data on the impact of these antiretroviral agents on pediatric body mass index (BMI). The ART options for older children living with HIV have expanded in recent years and are characterized by increased choice, tolerability and efficacy. Single-tablet, fixed-dose combination regimens containing TAF (with emtricitabine and elvitegravir/cobicistat) and DTG (with abacavir and lamivudine) are now licensed and increasingly prescribed for use in children ≥ 25 kg.4 Here, we report the first data to our knowledge of weight gain in ART-experienced children with HIV, following switch to TAF or DTG containing regimens. We conducted a single-center retrospective cohort study of ART-experienced children <18 years, living with HIV, switched to a regimen containing either TAF or DTG between January 2015 and June 2019. All children were reviewed quarterly at the tertiary hospital outpatient department, where height and weight were recorded along with ART prescription. BMI was documented according to age- and sex-matched standardized Z score (BMIz), to account for growth in childhood.5 The primary outcome was change in BMIz in the 12 months post-switch compared with the 12 months prior. Ethical approval was obtained (Governance Evidence Knowledge Outcomes Activity 34281). In total, 17 children were switched to TAF (n = 9) or DTG (n = 8); 1 patient switched to TAF then subsequently after >12 months to TAF/DTG with data from both changes included. The majority had a HIV viral load < 100 copies/mL (14/17, 82%) and CD4 count > 500 × 106 (16/17, 94%) at time of switch (Table 1). Of patients with BMIz data available, 100% (8/8) switched to TAF and 87.5% (7/8) switched to DTG had an increase in BMIz in the 12 months following switch. Mean BMIz increased in the 12 months following switch from –0.63 to –0.02 for TAF and from 0.29 to 0.52 for DTG. In patients switched to TAF, the mean BMI Z score increase following switch was significantly greater compared with the 12 months before switch (P = 0.037) (Table 1); BMIz stabilized in subsequent observable months (median 22 months total follow-up). HIV viral suppression (<40 copies/mL) following switch was maintained in 11 of 17 cases (65%); of the 6 cases where viral suppression was not maintained, 2 had a single viral blip (<200 copies/mL), 2 had periods <6 months of viral load >500 copies/mL associated with temporary suboptimal adherence and 1 patient (switched to TAF then TAF/DTG) had ongoing viral load >500 copies/mL > 6 months related to persistent poor adherence. TABLE 1. - Characteristics of Children Switched to TAF and DTG Containing Antiretroviral Regimens Patient Characteristics Antiretroviral Agent TAF (n = 9) DTG (n = 8) Age at switch (yr) (median [IQR]) 11.6 (8.7–13.7) 14.1 (12.8–15.2) Male (n [%]) 2 (22) 5 (63) Switch from ART regimen: (n [%]) PI 4 (44) 5 (63) ABC 6 (67) 7 (88) TDF 1 (11) 1 (13) NNRTI 4 (44) 4 (50) INSTI 2 (22) 1 (13) Switch to: (n [%]) EVG/COBI/FTC/TAF 9 (100) NA DTG/ABC/3TC NA 6 (75)§ HIV viral load <100 copies/mL at time of switch (n [%]) 7 (78) 7 (88) HIV viral load <100 copies/mL maintained post-switch (n [%]) 6 (67)* 5 (63)† CD4 >500 × 106/L at switch (n [%]) 9 (100) 7 (88) BMI n = 8‡ n = 8 BMIz at time of switch (mean [SD]) –0.63 (0.88) 0.29 (0.77) BMIz 12 months post-switch (mean [SD]) –0.02 (0.69) 0.52 (0.78) BMIz at last follow-up (mean [SD]) 0.01 (0.63) 0.73 (0.64) Duration of total follow-up, mo (median [IQR]) 22.2 (17.5–22.5) 30.2 (19.4–38.0) Change in BMIz in 12 mo pre-switch –0.02 0.16 Change in BMIz in 12 mo post-switch 0.61 0.24 Change in BMIz from switch to last follow-up 0.64 0.44 Absolute difference in BMIz change 12 mo post-switch vs. 12 mo pre-switch (95% CI) 0.64∥ (0.05–1.22) 0.08 (–0.17 to 0.32) P¶ 0.037∥ 0.49 *Two patients viral load >500 copies/mL during a period of follow-up (<6 months) associated with suboptimal adherence to ART during follow-up and 1 patient viral load >500 copies/mL for a prolonged period of follow-up (>6 months) associated with ongoing suboptimal adherence.†Two patients single viral blip between 100 and 200 copies/mL and 1 patient viral load persistently >500 copies/mL associated with ongoing suboptimal adherence.‡One patient switched to TAF had no follow-up BMI data available.§One patient each switched to TAF/FTC/DTG and TDF/FTC/DTG.¶Paired t test.∥Statistically significant difference.3TC indicates lamivudine; ABC, abacavir; CI, confidence interval; COBI, cobicistat; EVG, elvitegravir; FTC, emtricitabine; IQR, interquartile range; NA, not applicable; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; TDF, tenofovir disoproxil fumarate. With near-normal life expectancy for children and adolescents living with HIV in the current age of combination ART, it is likely that non-AIDS–defining illnesses including cardiovascular disease will be increasingly important in long-term management for this cohort. Weight gain during ART is known to impact on risk of cardiovascular disease in adults living with HIV.6 Similarly, childhood obesity is associated with increased risk of cardiovascular disease in adulthood. Our findings highlight the importance of monitoring BMI in children living with HIV following switch to TAF or INSTI containing ART regimens. The significance of ART-related weight gain on cardiovascular risk and long-term health outcomes in children living with HIV remains uncertain. More data are needed to understand the frequency, magnitude and underlying mechanism of weight gain in children and adolescents associated with these agents, as well as possible short- and long-term implications.

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