DeepDynaForecast: Phylogenetic-informed graph deep learning for epidemic transmission dynamic prediction.

In the midst of an outbreak or sustained epidemic, reliable prediction of transmission risks and patterns of spread is critical to inform public health programs. Projections of transmission growth or decline among specific risk groups can aid in optimizing interventions, particularly when resources are limited. Phylogenetic trees have been widely used in the detection of transmission chains and high-risk populations. Moreover, tree topology and the incorporation of population parameters (phylodynamics) can be useful in reconstructing the evolutionary dynamics of an epidemic across space and time among individuals. We now demonstrate the utility of phylodynamic trees for transmission modeling and forecasting, developing a phylogeny-based deep learning system, referred to as DeepDynaForecast. Our approach leverages a primal-dual graph learning structure with shortcut multi-layer aggregation, which is suited for the early identification and prediction of transmission dynamics in emerging high-risk groups. We demonstrate the accuracy of DeepDynaForecast using simulated outbreak data and the utility of the learned model using empirical, large-scale data from the human immunodeficiency virus epidemic in Florida between 2012 and 2020. Our framework is available as open-source software (MIT license) at github.com/lab-smile/DeepDynaForcast.

pH-sensitive dual-preventive siRNA-based nanomicrobicide reactivates autophagy and inhibits HIV infection in vaginal CD4+ cells.

Women are more susceptible to HIV transmission through unprotected heterosexual intercourse due to biological and social vulnerabilities. Intravaginal delivery of siRNAs targeting viral genes, host genes, or in combination has shown promising outcomes against HSV, HPV and HIV. Therefore, in this study, we designed, developed and evaluated a pH-sensitive RNAi-based combination nanomicrobide for the prevention/reduction of vaginal transmission of HIV. The nanomicrobide was composed of siRNA-PEI encapsulated PLGA-PEG nanoparticles (siRNA NP) loaded in a HEC gel dosage form with siRNA targeting host gene CCR5 and the viral gene Nef as a dual preventive strategy. Knocking down CCR5, a co-receptor for HIV could prevent HIV from attaching to and entering host cells and knocking down Nef could reactivate autophagy that was inhibited by Nef to improve the elimination of intracellular virus that escaped the first line of defense. The siRNA NP showed a desirable particle size and zeta potential for intravaginal delivery and a pH-dependent release profile whereby low amounts of siRNA was released under acidic vaginal conditions (vaginal fluid simulant; VFS, pH 4.2) (6.0 ± 0.4% released over 15 days) but significantly higher amounts of siRNA was released under neutral pH conditions (phosphate buffered saline; PBS, pH 7.4) (22.9 ± 0.4% released over 15 days). The CCR5-Nef-specific siRNA NP efficiently knocked down CCR5 and Nef protein expression by 43% and 63%, respectively, reactivated Nef-blocked autophagy and inhibited the replication of HIV in vitro (71.8% reduction in p24 expression). After being formulated into a gel dosage form, siRNA NP could be readily released from the gel, penetrate the vaginal epithelial layer, get taken up into the target cells and knockdown Nef and CCR5 without causing cytotoxicity in a vaginal mucosal co-culture model. Functionalization of siRNA NP with anti-CD4 antibody and loaded into a 0.5% HEC gel improved vaginal distribution and uptake of siRNA in a mouse model with distribution of siRNA restricted to the reproductive tract without any unwanted systemic uptake. The 0.5% HEC gel loaded with siRNA NP-(m)CD4 significantly downregulated approximately 40% of CCR5 protein in the lower vagina and 36% of CCR5 protein in the upper vaginal and cervical region. In contrast, 0.5% HEC gel loaded with siRNA NP-IgG did not result in significant gene knockdown.

AKT signaling modulates latent viral reservoir viability in HIV-1-infected blood-brain barrier pericytes.

Despite antiretroviral therapy (ART), chronic forms of HIV-associated neurocognitive disorders (HAND) affect an estimated 50% of individuals living with HIV, greatly impacting their quality of life. The prevailing theory of HAND progression posits that chronic inflammation arising from the activation of latent viral reservoirs leads to progressive damage in the central nervous system (CNS). Recent evidence indicates that blood-brain barrier (BBB) pericytes are capable of active HIV-1 infection; however, their latent infection has not been defined. Given their location and function, BBB pericytes are poised to be a key viral reservoir in the development of HAND. We present the first transcriptional analysis of uninfected, active, and latent human BBB pericytes, revealing distinct transcriptional phenotypes. In addition, we demonstrate that latent infection of BBB pericytes relies on AKT signaling for reservoir survival. These findings provide insight into the state of reservoir maintenance in the CNS during HIV-1 infection and provide novel targets for reservoir clearance.

A Three-Year Follow-Up of Bone Density Among Thai Adolescents With Perinatally Acquired HIV After Completion of Vitamin D and Calcium Supplementation.

PURPOSE: To determine changes in bone mineral density (BMD) and bone metabolism-related biomarkers among Thai adolescents with perinatally acquired HIV infection (PHIVA) at 3 years following completion of vitamin D and calcium (VitD/Cal) supplementation. METHODS: An observational follow-up study was conducted among PHIVA who received 48-week VitD/Cal supplementation (either high-dose [3,200 IU/1,200 mg daily] or standard-dose [400 IU/1,200 mg daily]). Lumbar spine BMD (LSBMD) was assessed by dual-energy x-ray absorptiometry. Serum 25-hydroxyvitamin D, intact parathyroid hormone, and bone turnover markers were measured. Changes in LSBMD z-scores and other bone parameters at 3 years after stopping VitD/Cal supplementation compared with baseline or week 48 of supplementation were assessed among participants previously receiving high-dose and standard-dose VitD/Cal supplementation. RESULTS: Of 114 enrolled PHIVA, 46% and 54% had previously received high-dose and standard-dose VitD/Cal supplementation, respectively. The median age was 20 years; 53% were male. At 3 years after completion of VitD/Cal supplementation, we observed a significant decline in 25-hydroxyvitamin D and increase in intact parathyroid hormone but no significant rebounds of C-terminal telopeptides of collagen type I and procollagen type I amino-terminal propeptides and no significant changes in LSBMD z-scores among PHIVA in both treatment groups, compared with the measurements at week 48 of supplementation. Notably, LSBMD z-scores at 3 years after stopping VitD/Cal supplements were not significantly altered from baseline evaluations in both PHIVA groups. DISCUSSION: Three years after completion of high-dose or standard-dose VitD/Cal supplementation, LSBMD z-scores of our Thai PHIVA were not significantly changed from baseline and week 48 of supplementation. VitD/Cal supplementation of PHIVA during periods of peak bone mass accrual may have sustained and long-term skeletal benefits.

Raltegravir 100 mg granulado para profilaxia da transmissão vertical do HIV em crianças com alto risco de exposição ao HIV / Raltegravir 100 mg granules for transmission prophylaxis vertical of HIV in children at high risk of exposure to HIV

INTRODUÇÃO: A transmissão materna ou transmissão vertical do HIV é um importante fator contribuinte para a pandemia do HIV. O vírus do HIV pode ser transmitido de uma mulher vivendo com HIV para seu bebê durante a gravidez, trabalho de parto ou parto, ou após o parto através da amamentação. Sem tratamento, a infecção pelo HIV em lactentes e crianças pequenas resulta em mortalidade precoce ou cria uma condição crônica vitalícia que aumenta muito a morbidade, reduz a expectativa de vida, impõe um grande fardo à criança e à família e contribui para perdas humanas, sociais e econômicas. PERGUNTA: O uso do medicamento raltegravir 100 mg granulado é eficaz e seguro para a profilaxia da transmissão vertical do HIV em crianças com alto risco de exposição ao HIV? EVIDÊNCIAS CLÍNICAS: Das 417 referências identificadas nas quatro bases científicas consultadas, apenas um estudo contribuiu para a análise do uso de raltegravir 100 mg granulado em crianças expostas ao HIV por transmissão vertical. Este estudo não foi realizado para mensurar a eficácia, contudo nenhum dos neonatos incluídos em qualquer uma das duas coortes foi diagnosticado com HIV. O raltegravir granulado foi bem tolerado e apenas um evento adverso encontrado foi possivelmente associado a ele. O estudo demonstrou que foi possível formular um regime de raltegravir granulado que pode ser administrado de maneira segura em neonatos expostos ao HIV: 1,5 mg/kg diariamente até o sétimo dia de vida; 3 mg/kg duas vezes ao dia de oito a 28 dias de vida; e 6 mg/kg duas vezes ao dia de quatro a seis semanas de vida. No entanto, considerando as características dos participantes incluídos no estudo, o raltegravir granulado não é recomendado para prematuros ou para recém-nascidos com menos de 2 kg. De acordo com o sistema GRADE, a qualidade da evidência foi considerada muito baixa para os desfechos segurança e tolerabilidade. AVALIAÇÃO ECONÔMICA: Foi construído um modelo de árvore de decisão do raltegravir 100 mg granulado (RAL) comparado à nevirapina (NVP), para profilaxia da transmissão vertical do HIV em recém-nascidos de alto risco, com idade gestacional igual ou maior a 37 semanas. A perspectiva adotada foi a do SUS e o horizonte temporal foi de quatro semanas (tempo de duração da profilaxia). O custo incremental da profilaxia com raltegravir foi de R$ 1.088,62. Considerando os parâmetros utilizados, principalmente a maior resistência encontrada à nevirapina, a profilaxia com raltegravir se apresentou como mais efetiva e a razão de custo-efetividade incremental (ICER) resultou em R$ 6.538,26 por caso evitado de infecção pelo HIV em neonato no cenário base. Os resultados de benefício monetário líquido (NMB) encontrados foram de R$ 32.824,68 para raltegravir e R$ 27.930,00 para a nevirapina. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: Foi realizada análise do impacto orçamentário com a simulação da incorporação do esquema contendo raltegravir 100 mg granulado, na perspectiva do SUS, considerado um horizonte temporal de 5 anos, comparado ao esquema contendo nevirapina 10 mg/ml para a profilaxia da transmissão vertical do HIV em crianças com alto risco de exposição ao HIV. Considerando um market share de 100% logo no primeiro ano de incorporação, o gasto total estimado para a compra do medicamento raltegravir 100 mg granulado em um horizonte temporal de 5 anos seria de R$ 6.028.223,73. Foi estimado que o uso do novo esquema de profilaxia contendo raltegravir 100 mg granulado em substituição ao esquema anterior contendo nevirapina, resultará em um impacto orçamentário incremental total de R$ 6.098.699,79 em 5 anos. RECOMENDAÇÕES INTERNACIONAIS: Foram consultadas as agências internacionais de ATS National Institute for Health and Care Excellence (NICE), Canadian Agency for Drugs and Technologies in Health (CADTH), Pharmaceutical Benefits Advisory Committee (PBAC) e Scottish Medicines Consortium (SMC) sobre o raltegravir granulado de 100 mg. Contudo, não foram encontrados documentos para a apresentação de interesse. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: No horizonte considerado nesta análise, não foram detectadas tecnologias potenciais para profilaxia da transmissão vertical do HIV em crianças com alto risco de exposição ao vírus. CONSIDERAÇÕES FINAIS: Os dados disponíveis até o momento sobre o uso de raltegravir 100 mg granulado na profilaxia da transmissão vertical do HIV em crianças expostas de alto risco são provenientes de ensaio clínico de fase 1, não comparativo, sem grupo controle, que demonstrou que o raltegravir granulado foi bem tolerado e que pode ser administrado de maneira segura em neonatos expostos ao HIV. Por outro lado, este estudo não foi realizado para mensurar a eficácia. Na avaliação econômica, a profilaxia com raltegravir se apresentou mais efetiva e a ICER resultou em R$ 6.538,26 por caso evitado de infecção pelo HIV em neonato no cenário base. Os resultados de benefício monetário líquido encontrados foram de R$ 32.824,68 para raltegravir e R$ 27.930,00 para a nevirapina. Já a análise do impacto orçamentário, considerando um market share de 100% no primeiro ano de incorporação, apontou que o gasto total estimado para a compra do medicamento raltegravir 100 mg granulado em um horizonte temporal de 5 anos seria de R$ 6.028.223,73. Foi estimado que o uso do novo esquema de profilaxia contendo raltegravir 100 mg granulado, em substituição ao esquema anterior contendo nevirapina, resultará em um impacto orçamentário incremental total de R$ 6.098.699,79 em 5 anos. PERSPECTIVA DO PACIENTE: Foi aberta chamada pública nº 06/2023, no período entre 13/02/2023 e 26/02/2023, para interessados em participar da Perspectiva do Paciente para este tema. Entretanto, não houve inscrições. RECOMENDAÇÃO PRELIMINAR DA CONITEC: O Plenário da Conitec, em sua 116ª Reunião Ordinária, no dia 15 de março de 2023, deliberou que a matéria fosse disponibilizada em Consulta Pública com recomendação preliminar favorável à incorporação de raltegravir 100 mg granulado para profilaxia da transmissão vertical do HIV em crianças com alto risco de exposição ao HIV no SUS. Os membros da Conitec consideraram que apesar da escassez de evidências disponíveis no momento, trata-se de uma população pouco estudada em ensaios clínicos e com uma necessidade de saúde relacionada à alta resistência que atualmente se tem com o uso da alternativa disponível no SUS, a nevirapina. Dessa forma, entendeuse que a incorporação da apresentação farmacêutica granulada do raltegravir seria apropriada para essa faixa etária dos pacientes atendidos no SUS. CONSULTA PÚBLICA: Foi realizada entre 19/04/2023 e 08/05/2023 a Consulta Pública nº 12/2023. Foram recebidas três contribuições, todas concordantes com a recomendação preliminar, sendo uma técnico-científica e duas sobre experiência ou opinião. A única contribuição técnico-científica foi enviada por pessoa física e profissional de saúde. Foi anexado um documento elaborado pela Comissão de Farmácia e Terapêutica da Secretaria Estadual de Saúde de Minas Gerais, que sugeriu um período mais longo para implementação do protocolo de HIV nos estados e municípios, considerando a logística da distribuição e dispensação do novo medicamento. Não foram recebidas informações adicionais sobre evidências clínicas, avaliação econômica e impacto orçamentário. As duas contribuições de experiência e opinião foram enviadas por pessoas físicas, sendo uma de familiar, amigo ou cuidador de paciente e a outra de profissional de saúde, sem nenhum documento anexado. Citou-se os seguintes potenciais benefícios com raltegravir granulado: melhor profilaxia para recém-nascidos de alto risco; maior facilidade de administração; maior barreira genética; apresentação farmacêutica que melhora a adesão ao tratamento. Por fim, considerou-se que as contribuições recebidas na CP estiveram alinhadas com a recomendação preliminar da Conitec, não justificando mudança de entendimento sobre o tema. RECOMENDAÇÃO FINAL DA CONITEC: Os membros do Comitê de Medicamentos presentes na 119ª Reunião Ordinária da Conitec, realizada no dia 31 de maio de 2023, deliberaram por unanimidade, recomendar a incorporação do raltegravir 100 mg granulado para profilaxia da transmissão vertical do HIV em crianças com alto risco de exposição ao HIV no SUS. Os membros mantiveram o entendimento que culminou na recomendação inicial sobre o tema. Assim, foi assinado o Registro de Deliberação nº 828/2023. DECISÃO: Incorporar, no âmbito do Sistema Único de Saúde - SUS, o raltegravir 100 mg granulado para profilaxia da transmissão vertical do HIV em crianças com alto risco de exposição ao HIV, publicada no Diário Oficial da União nº 126, seção 1, página 118, em 5 de julho de 2023.

Human seminal plasma stimulates the migration of CD11c+ mononuclear phagocytes to the apical side of the colonic epithelium without altering the junctional complexes in an ex vivo human intestinal model.

Introduction: Human immunodeficiency virus type 1 (HIV) transmission mostly occurs through the genital and intestinal mucosae. Although HIV-1 transmission has been extensively investigated, gaps remain in understanding the initial steps of HIV entry through the colonic mucosa. We previously showed that HIV can selectively trigger mononuclear phagocytes (MNP) to migrate within colonic epithelial cells to sample virions. Mucosal exposure to human seminal plasma (HSP), rich in pro- and anti-inflammatory cytokines, chemokines and growth factors, may as well induce alterations of the colonic mucosa and recruit immune cells, hence, affecting pathogen sampling and transmission. Methods: Here, we studied the role of HSP on the paracellular intestinal permeability by analyzing the distribution of two proteins known to play a key role in controlling the intestinal barrier integrity, namely the tight junctions-associated junctional adhesion molecule (JAM-A) and the adherents junction associated protein E-cadherin (E-CAD), by immunofluorescence and confocal microscopy. Also, we evaluated if HSP promotes the recruitment of MNP cells, specifically, the CD11c and CD64 positive MNPs, to the apical side of the human colonic mucosa. At this scope, HSP of HIV-infected and uninfected individuals with known fertility status was tested for cytokines, chemokines and growth factors concentration and used in an ex vivo polarized colonic tissue culture system to mimic as closely as possible the physiological process. Results: HSP showed statistically significant differences in cytokines and chemokines concentrations between the three groups of donors, i.e. HIV infected, or uninfected fertile or randomly identified. Nevertheless, we showed that in the ex vivo tissue culture HSP in general, neither affected the morphological structure of the colonic mucosa nor modulated the paracellular intestinal permeability. Interestingly, CD11c+ MNP cells migrated to the apical surface of the colonic epithelium regardless, if incubated with HIV-infected or -uninfected HSPs, while CD64+ MNP cells, did not change their distribution within the colonic mucosa. Discussion: In conclusion, even if HSP did not perturb the integrity of the human colonic mucosa, it affected the migration of a specific subset of MNPs that express CD11c towards the apical side of the colonic mucosa, which in turn may be involved in pathogen sampling.

Highlights From CROI, the Conference on Retroviruses and Opportunistic Infections-Postexposure Prophylaxis for Sexually Transmitted Infections, a New Protease Inhibitor for COVID-19, Goals for Preventing HIV Transmission, and More.

This Medical News Q&A discusses research highlights from the recent Conference on Retroviruses and Opportunistic Infections.

Geographic mobility and its impact on sexual health and ongoing HIV transmission among migrant latinx men who have sex with men.

An understudied social process that may determine variable HIV risk, testing, and linkage to care is geographic mobility, including immigration as well as short-term mobility, especially among sexual minority populations. We aimed to assess how geographic mobility over the lifecourse between Latin America and the U.S., and within the U.S., was linked to sexual risk and health behaviors among Latinx migrant men who have sex with men (MSM) in San Bernardino County, California. Qualitative analysis of 16 semi-structured interviews revealed four major domains of influence on participants' sexual risk behaviors. At the micro level, these included social environment/interpersonal factors (e.g., family and peer support) and geographic factors and pathways (e.g., migration journey to the U.S.). At the macro level data centered on cultural factors (e.g., gender norms in home country) and structural factors (e.g., HIV healthcare). Our results can illuminate and promote effective health policies and HIV reduction efforts for Latinx migrant MSM in metro areas.

Vulnerability of the young university population to HIV/AIDS and other sexually transmitted infections

Introduction: Brazilian universities receive annually thousands of young people who experience situations of vulnerability to the human immunodeficiency virus, sexually transmitted infections, and viral hepatitis. Objective: The aim of the present study was to analyze the secondary data obtained from the attendance record of the rapid testing campaign for these health problems at a federal university in the state of Minas Gerais, Brazil, in 2019. Methods: A cross-sectional study was conducted with secondary data of students (n=1,113) obtained from the standard attendance form by the Ministry of Health during the campaigns Fique Sabendo (Be Aware) in the period between November 25 and 29, 2019. Analyses were performed with the support of the Statistical Package for Social Sciences program, with the calculation of absolute and relative frequencies. Pearson's chi-square test (5%) was used for comparison. Results: The results revealed a young, heterosexual, white profile. More than half reported having consumed alcohol and drugs in their lives. Other findings were the non-use of condoms with steady partners (18.1%) and occasional partners (21.3%), oral sex (86.8%), and unprotected sex in the last intercourse (45.6%). Most declared never being tested for human immunodeficiency virus (74.5%), syphilis (67.4%), hepatitis B (76.1%), or hepatitis C (77.0%). Conclusion: The university population is vulnerable to human immunodeficiency virus and other sexually transmitted infections due to the number of sexual partners and discontinued use of condoms with occasional partners. Such vulnerability is increased by the use of alcohol and other drugs

The role of IL-1ß during human immunodeficiency virus type 1 infection.

Interleukin (IL)-1ß is a key innate cytokine that is essential for immune activation and promoting the inflammatory process. However, abnormal elevation in IL-1ß levels has been associated with unwanted clinical outcomes. IL-1ß is the most extensively studied cytokine among the IL-1 family of cytokines and its role in pathology is well established. During the course of human immunodeficiency virus type 1 (HIV-1) infection, the level of this proinflammatory cytokine is increased in different anatomical compartments, particularly in lymphatic tissues, and this elevation is associated with disease progression. The aim of this review is to address the pathological roles play by IL-1ß in the light of enhancing HIV-1 replication, driving immune cell depletion, and chronic immune activation. The role of IL-1ß in HIV-1 transmission (sexually or vertically 'from mother-to-child') will also be discussed. Additionally, the impact of the available antiretroviral therapy regimens on the levels of IL-1ß in HIV-1 treated patients is also discussed. Finally, we will provide a glance on how IL-1ß could be targeted as a therapeutic strategy.

Determinants of mother to child HIV transmission (HIV MTCT); a case control study in governmental health centers of East Gojjam Zone, Northwest Ethiopia, 2019.

BACKGROUND: Mother to child human immune virus (HIV) transmission is the passage of HIV from mother to her child during pregnancy, labor, delivery or breast-feeding. The objective of this study was to identify determinants of mother to child HIV transmission among HIV exposed infants who were born from HIV positive mothers at Governmental health centers of East Gojjam Zone, Northwestern Ethiopia, 2019. METHODS: A case-control study was conducted on 210(42 cases and 168 controls) from April 1 to 30/ 2019. All cases were included in the study. Controls were selected by simple random sampling. Secondary data were extracted by using checklists from the document of 8 health centers ART register book, antenatal care (ANC) follow up register book, PMTCT service registration log book charts and infant dried blood sample (DBS) tally sheets. After Bivariable logistic regression analysis, all variables with p-value [Formula: see text] 0.25 were entered into multivariable logistic regression and p value < 0.05 considered as significantly associated with the outcome variable. RESULTS: HIV exposed infants who were being rural dweller versus (vs) those infants who were being urban dweller [adjusted odds ratio (AOR) = 3.73; 95% CI; 1.27-10.69], have no history of antenatal care follow up of HIV exposed infants' HIV positive mothers versus (vs) those mothers who have been having history of ANC follow up [ AOR = 5.0;95%CI; 2.02-12.16] and initial CD4 count of HIV infants' mothers [Formula: see text] vs those mothers whose CD4 > 350 [AOR = 2.7;95%CI;1.35-5.52] were significantly associated with HIV infection. CONCLUSION: Mother to child HIV transmission was significantly associated with history of ANC follow up of exposed infants' mothers and initial CD4 counts of mothers. Strong effort should be made to further increase the ANC service utilization of HIV positive pregnant women.

Using phylogenetics to infer HIV-1 transmission direction between known transmission pairs.

Inferring the transmission direction between linked individuals living with HIV provides unparalleled power to understand the epidemiology that determines transmission. Phylogenetic ancestral-state reconstruction approaches infer the transmission direction by identifying the individual in whom the most recent common ancestor of the virus populations originated. While these methods vary in accuracy, it is unclear why. To evaluate the performance of phylogenetic ancestral-state reconstruction to determine the transmission direction of HIV-1 infection, we inferred the transmission direction for 112 transmission pairs where transmission direction and detailed additional information were available. We then fit a statistical model to evaluate the extent to which epidemiological, sampling, genetic, and phylogenetic factors influenced the outcome of the inference. Finally, we repeated the analysis under real-life conditions with only routinely available data. We found that whether ancestral-state reconstruction correctly infers the transmission direction depends principally on the phylogeny's topology. For example, under real-life conditions, the probability of identifying the correct transmission direction increases from 32%-when a monophyletic-monophyletic or paraphyletic-polyphyletic tree topology is observed and when the tip closest to the root does not agree with the state at the root-to 93% when a paraphyletic-monophyletic topology is observed and when the tip closest to the root agrees with the root state. Our results suggest that documenting larger differences in relative intrahost diversity increases our confidence in the transmission direction inference of linked pairs for population-level studies of HIV. These findings provide a practical starting point to determine our confidence in transmission direction inference from ancestral-state reconstruction.

Growth improvement following antiretroviral therapy initiation in children with perinatally-acquired HIV diagnosed in older childhood in Zimbabwe: a prospective cohort study.

BACKGROUND: Children who initiate antiretroviral therapy (ART) before age 5 years can recover height and weight compared to uninfected peers, but growth outcomes are unknown for children initiating ART at older ages. We investigated factors associated with growth failure at ART initiation and modelled growth by age on ART. METHODS: We conducted secondary analysis of cohort of children aged 6-15 years late-diagnosed with HIV in Harare, Zimbabwe, with entry at ART initiation in 2013-2015. Factors associated with height-for-age (HAZ), weight-for-age (WAZ) and BMI-for-age (BAZ) z-scores <- 2 (stunting, underweight and wasting respectively) at ART initiation were assessed using multivariable logistic regression. These outcomes were compared at ART initiation and 12 month follow-up using paired t-tests. HAZ and BAZ were modelled using restricted cubic splines. RESULTS: Participants (N = 302; 51.6% female; median age 11 years) were followed for a median of 16.6 months (IQR 11.0-19.8). At ART initiation 34.8% were stunted, 34.5% underweight and 15.1% wasted. Stunting was associated with age ≥ 12 years, CD4 count < 200 cells/µl, tuberculosis (TB) history and history of hospitalisation. Underweight was associated with older age, male sex and TB history, and wasting was associated with older age, TB history and hospitalisation. One year post-initiation, t-tests showed increased WAZ (p = 0.007) and BAZ (p = 0.004), but no evidence of changed HAZ (p = 0.85). Modelling showed that HAZ and BAZ decreased in early adolescence for boys on ART, but not girls. CONCLUSION: Stunting and underweight were prevalent at ART initiation among late-diagnosed children, and HAZ did not improve after 1 year. Adolescent boys with perinatally acquired HIV and late diagnosis are particularly at risk of growth failure in puberty.