Earlier Antiretroviral Therapy Initiation and Decreasing Mortality Among HIV-infected Infants Initiating Antiretroviral Therapy Within 3 Months of Age in South Africa, 2006–2017

Iyun, Victoria; Technau, Karl-Günter; Eley, Brian; Rabie, Helena; Boulle, Andrew; Fatti, Geoffrey; Egger, Matthias; Tanser, Frank; Wood, Robin; Fairlie, Lee; Cotton, Mark F.; Davies, Mary‐Ann

doi:10.1097/inf.0000000000002516

Cited by 19 publications

(27 citation statements)

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“…With these limitations, our study analyzes an issue that is very important for the future management of PHIV, because many young adolescents and children born with HIV infections now have the possibility to grow old, thanks to the high efficacy of modern ART and drug policies that facilitate the access and supply of drugs, even in limited resource settings [ 37 ]. On the contrary, in the past, due to high HIV-related mortality in childhood [ 38 ], many PHIVs did not have the chance to reach adulthood and, therefore, there are no historical data on the impact of long-term treatment and on how it is best to treat them over time. This work might have a bearing on potentially greater burden HIV settings, such as Africa, and also in industrialized countries, where mother to child transmission has not been eliminated yet [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Switching to Integrase Inhibitors Unlinked to Weight Increase in Perinatally HIV-Infected Young Adults and Adolescents: A 10-Year Observational Study

et al. 2020

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An unexpected increase in weight gain has recently been reported in the course of integrase strand transfer inhibitors (INSTI) treatment. The possibility of this effect in people who are perinatally infected with HIV (PHIV) and thus exposed to lifelong therapy needs to be explored. This is a retrospective multicenter case-control study. Adults with PHIV followed between 2010 and 2019 in two outpatient services in Northern Italy were included if they had at least two weight measures in two successive years of observation. Patients were considered as cases if they were switched to INSTI (INSTI group), or controls if they were never exposed to INSTI (non-INSTI group). The date of the switch in cases was considered to be the baseline (T0), while it was randomly selected in controls. Mixed effect models were used to assess the weight changes in INSTI and non-INSTI groups. A total of 66 participants, 50.0% women, 92.4% Caucasian, were included. Median follow-up was 9 years (range 2–10): 4 years (range 1–8) before and 3 (range 1–9) after-T0. Mean age at the last study visit was 27.3 (±4.8) years, and mean CD4+ T-cells were 820.8 (±323.6) cells/mm3. Forty-five patients were switched to INSTI during the study, while 21 remained in the non-INSTI group. The INSTI group experienced a mean increase (pre-post T0) in bodyweight of 0.28 kg/year (95% CI − 0.29; 0.85, p = 0.338), while in the non-INSTI group, the mean increase was 0.36 kg/year (95% CI − 0.47; 1.20, p = 0.391), without a significant difference between groups (p for interaction between time and treatment regimen = 0.868). Among patients on INSTI, the weight gain after T0 was higher than pre-T0, amounting to +0.28 kg/year (95% CI − 0.29; 0.85), although this difference did not reach significance (p = 0.337). PHIV switched to an INSTI-based regimen did not experience an excessive weight gain compared to those who were treated with a non-INSTI based regimen in our cohort.

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Section: Discussionmentioning

confidence: 99%

Switching to Integrase Inhibitors Unlinked to Weight Increase in Perinatally HIV-Infected Young Adults and Adolescents: A 10-Year Observational Study

et al. 2020

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“…4 Plasma ferritin adjusted for inflammation [35]. 5 Adjusted plasma ferritin < 15 µg/L [24]. 6 Plasma soluble transferrin receptor > 8.3 mg/L [28].…”

Section: Anemiamentioning

confidence: 99%

“…4 Median (inter-quartile range) (all such values). 5 RAE, retinol activity equivalents (1 RAE = 1 µg retinol = 12 µg beta-carotene = 24 µg α-carotene) [40]. 6 No EAR established; adequate intake (AI) values used [40].…”

Section: Selected Nutrient Intakementioning

confidence: 99%

“…Worldwide, an estimated 1.7 million children younger than 15 years old are living with the human immunodeficiency virus (HIV) (HIV+), with sub-Saharan Africa most affected [ 1 ]. Children with perinatally acquired HIV benefit from very early diagnosis and treatment [ 2 , 3 ], which significantly improves mortality and reduces morbidity [ 4 , 5 ]. Nevertheless, HIV+ children remain vulnerable to complications related to HIV or lifelong antiretroviral therapy (ART) [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Median (inter-quartile range) (all such values) 4. HIV and low iron stores n = 39, and HIV and iron sufficient non-anemic n = 39, as start date unknown for three children 5. Formal housing represents a brick house, while informal housing represents a Wendy house or dwelling built with scrap building material and typically not equipped with water and/or electricity.…”

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Examining Associations of HIV and Iron Status with Nutritional and Inflammatory Status, Anemia, and Dietary Intake in South African Schoolchildren

et al. 2021

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The etiology of multifactorial morbidities such as undernutrition and anemia in children living with the human immunodeficiency virus (HIV) (HIV+) on antiretroviral therapy (ART) is poorly understood. Our objective was to examine associations of HIV and iron status with nutritional and inflammatory status, anemia, and dietary intake in school-aged South African children. Using a two-way factorial case-control design, we compared four groups of 8 to 13-year-old South African schoolchildren: (1) HIV+ and low iron stores (inflammation-unadjusted serum ferritin ≤40 µg/L), n = 43; (2) HIV+ and iron sufficient non-anemic (inflammation-unadjusted serum ferritin >40 µg/L, hemoglobin ≥115 g/L), n = 41; (3) children without HIV (HIV-ve) and low iron stores, n = 45; and (4) HIV-ve and iron sufficient non-anemic, n = 45. We assessed height, weight, plasma ferritin (PF), soluble transferrin receptor (sTfR), plasma retinol-binding protein, plasma zinc, C-reactive protein (CRP), α-1-acid glycoprotein (AGP), hemoglobin, mean corpuscular volume, and selected nutrient intakes. Both HIV and low iron stores were associated with lower height-for-age Z-scores (HAZ, p < 0.001 and p = 0.02, respectively), while both HIV and sufficient iron stores were associated with significantly higher CRP and AGP concentrations. HIV+ children with low iron stores had significantly lower HAZ, significantly higher sTfR concentrations, and significantly higher prevalence of subclinical inflammation (CRP 0.05 to 4.99 mg/L) (54%) than both HIV-ve groups. HIV was associated with 2.5-fold higher odds of iron deficient erythropoiesis (sTfR >8.3 mg/L) (95% CI: 1.03–5.8, p = 0.04), 2.7-fold higher odds of subclinical inflammation (95% CI: 1.4–5.3, p = 0.004), and 12-fold higher odds of macrocytosis (95% CI: 6–27, p < 0.001). Compared to HIV-ve counterparts, HIV+ children reported significantly lower daily intake of animal protein, muscle protein, heme iron, calcium, riboflavin, and vitamin B12, and significantly higher proportions of HIV+ children did not meet vitamin A and fiber requirements. Compared to iron sufficient non-anemic counterparts, children with low iron stores reported significantly higher daily intake of plant protein, lower daily intake of vitamin A, and lower proportions of inadequate fiber intake. Along with best treatment practices for HIV, optimizing dietary intake in HIV+ children could improve nutritional status and anemia in this vulnerable population. This study was registered at clinicaltrials.gov as NCT03572010.

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Global HIV mortality trends among children on antiretroviral treatment corrected for under‐reported deaths: an updated analysis of the International epidemiology Databases to Evaluate AIDS collaboration

et al. 2021

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Introduction The Joint United Nations Programme on HIV/AIDS (UNAIDS) projections of paediatric HIV prevalence and deaths rely on the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium for mortality estimates among children living with HIV (CHIV) receiving antiretroviral therapy (ART). Previous estimates, based on data through 2014, may no longer be accurate due to expanded paediatric HIV care and treatment eligibility, and the possibility of unreported deaths in CHIV considered lost to follow‐up (LTFU). We therefore estimated all‐cause mortality and its trends in CHIV (<15 years old) on ART using extended and new IeDEA data. Methods We analysed (i) IeDEA observational data from CHIV in routine care globally, and (ii) novel data from an IeDEA tracing study that determined outcomes in a sample of CHIV after being LTFU in southern Africa. We included 45,711 CHIV on ART during 2004 to 2017 at 72 programmes in Africa, Asia‐Pacific and Latin America. We used mixed effects Poisson regression to estimate mortality by age, sex, CD4 at ART start, time on ART, region and calendar year. For Africa, in an adjusted analysis that accounts for unreported deaths among those LTFU, we first modified the routine data by simulating mortality outcomes within six months after LTFU, based on a Gompertz survival model fitted to the tracing data ( n = 221). Results Observed mortality rates were 1.8 (95% CI: 1.7 to 1.9) and 9.4 (6.3 to 13.4) deaths per 100 person‐years in the routine and tracing data, respectively. We found strong evidence of higher mortality at shorter ART durations, lower CD4 values, and in infancy. Averaging over covariate patterns, the adjusted mortality rate was 54% higher than the unadjusted rate. In unadjusted analyses, mortality reduced by an average 60% and 73% from 2005 to 2017, within and outside of Africa, respectively. In the adjusted analysis for Africa, this temporal reduction was 42%. Conclusions Mortality rates among CHIV have decreased substantially over time. However, when accounting for worse outcomes among those LTFU, mortality estimates increased and temporal improvements were slightly reduced, suggesting caution in interpreting analyses based only on programme data. The improved and updated IeDEA estimates on mortality among CHIV on ART support UNAIDS efforts to accurately model global HIV statistics.

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Earlier Antiretroviral Therapy Initiation and Decreasing Mortality Among HIV-infected Infants Initiating Antiretroviral Therapy Within 3 Months of Age in South Africa, 2006–2017

Cited by 19 publications

References 20 publications

Switching to Integrase Inhibitors Unlinked to Weight Increase in Perinatally HIV-Infected Young Adults and Adolescents: A 10-Year Observational Study

Switching to Integrase Inhibitors Unlinked to Weight Increase in Perinatally HIV-Infected Young Adults and Adolescents: A 10-Year Observational Study

Examining Associations of HIV and Iron Status with Nutritional and Inflammatory Status, Anemia, and Dietary Intake in South African Schoolchildren

Global HIV mortality trends among children on antiretroviral treatment corrected for under‐reported deaths: an updated analysis of the International epidemiology Databases to Evaluate AIDS collaboration

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