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Analytical treatment interruption (ATI) is widely acknowledged as an essential component of studies to advance our understanding of HIV cure, but discussion has largely been focused on adults. To address this gap, we reviewed evidence related to the safety and utility of ATI in paediatric populations. Three randomised ATI trials using CD4 T-cell and clinical criteria to guide restart of antiretroviral therapy (ART) have been conducted. These trials found low risks associated with ATI in children, including reassuring findings pertaining to neurocognitive outcomes. Similar to adults treated during acute infection, infants treated early in life have shifts in virological and immunological parameters that increase their likelihood of achieving ART-free viral control. Early ART limits the size and diversity of the viral reservoir and shapes effective innate and HIV-specific humoral and cellular responses. Several cases of durable ART-free viral control in early treated children have been reported. We recommend that, where appropriate for the study question and where adequate monitoring is available, ATI should be integrated into ART-free viral control research in children living with HIV. Paediatric participants have the greatest likelihood of benefiting and potentially the most years to prospectively realise those benefits. Excluding children from ATI trials limits the evidence base and delays access to interventions.
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In perinatal HIV infection, early antiretroviral therapy (ART) initiation is recommended but questions remain regarding infant immune responses to HIV and its impact on immune development. Using single cell transcriptional and phenotypic analysis we evaluated the T cell compartment at pre-ART initiation of infants with perinatally acquired HIV from Maputo, Mozambique (Towards AIDS Remission Approaches cohort). CD8+ T cell maturation subsets exhibited altered distribution in HIV exposed infected (HEI) infants relative to HIV exposed uninfected infants with reduced naive, increased effectors, higher frequencies of activated T cells, and lower frequencies of cells with markers of self-renewal. Additionally, a cluster of CD8+ T cells identified in HEI displayed gene profiles consistent with cytotoxic T lymphocytes and showed evidence for hyper expansion. Longitudinal phenotypic analysis revealed accelerated maturation of CD8+ T cells was maintained in HEI despite viral control. The results point to an HIV-directed immune response that is likely to influence reservoir establishment.
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In Mozambique, targeted provider-initiated HIV testing and counselling (PITC) is recommended where universal PITC is not feasible, but its effectiveness depends on healthcare providers' training. This study aimed to evaluate the effect of a Ministry of Health training module in targeted PITC on the HIV positivity yield, and identify factors associated with a positive HIV test. We conducted a single-group pre-post study between November 2018 and November 2019 in the triage and emergency departments of four healthcare facilities in Manhiça District, a resource-constrained semi-rural area. It consisted of two two-month phases split by a one-week targeted PITC training module ("observation phases"). The HIV positivity yield of targeted PITC was estimated as the proportion of HIV-positive individuals among those recommended for HIV testing by the provider. Additionally, we extracted aggregated health information system data over the four months preceding and following the observation phases to compare yield in real-world conditions ("routine phases"). Logistic regression analysis from observation phase data was conducted to identify factors associated with a positive HIV test. Among the 7,102 participants in the pre- and post-training observation phases (58.5% and 41.5% respectively), 68% were women, and 96% were recruited at triage. In the routine phases with 33,261 individuals (45.8% pre, 54.2% post), 64% were women, and 84% were seen at triage. While HIV positivity yield between pre- and post-training observation phases was similar (10.9% (269/2470) and 11.1% (207/1865), respectively), we observed an increase in yield in the post-training routine phase for women in triage, rising from 4.8% (74/1553) to 7.3% (61/831) (Yield ratio = 1.54; 95%CI: 1.11-2.14). Age (25-49 years) (OR = 2.43; 95%CI: 1.37-4.33), working in industry/mining (OR = 4.94; 95%CI: 2.17-11.23), unawareness of partner's HIV status (OR = 2.50; 95%CI: 1.91-3.27), and visiting a healer (OR = 1.74; 95%CI: 1.03-2.93) were factors associated with a positive HIV test. Including these factors in the targeted PITC algorithm could have increased new HIV diagnoses by 2.6%. In conclusion, providing refresher training and adapting the current targeted PITC algorithm through further research can help reach undiagnosed PLHIV, treat all, and ultimately eliminate HIV, especially in resource-limited rural areas.
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Consejo , Infecciones por VIH , Personal de Salud , Humanos , Mozambique/epidemiología , Femenino , Masculino , Adulto , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Personal de Salud/educación , Persona de Mediana Edad , Prueba de VIH/métodos , Adulto Joven , Adolescente , Tamizaje Masivo/métodos , Triaje/métodos , Servicio de Urgencia en HospitalRESUMEN
In Mozambique, targeted provider-initiated HIV testing and counselling (PITC) is recommended where universal PITC is not feasible, but its effectiveness depends on healthcare providers' training. This study aimed to evaluate the effect of a Ministry of Health training module in targeted PITC on the HIV positivity yield, and identify factors associated with a positive HIV test. We conducted a single-group pre-post study between November 2018 and November 2019 in the triage and emergency departments of four healthcare facilities in Manhiça District, a resource-constrained semi-rural area. It consisted of two two-month phases split by a one-week targeted PITC training module ("observation phases"). The HIV positivity yield of targeted PITC was estimated as the proportion of HIV-positive individuals among those recommended for HIV testing by the provider. Additionally, we extracted aggregated health information system data over the four months preceding and following the observation phases to compare yield in real-world conditions ("routine phases"). Logistic regression analysis from observation phase data was conducted to identify factors associated with a positive HIV test. Among the 7,102 participants in the pre- and post-training observation phases (58.5% and 41.5% respectively), 68% were women, and 96% were recruited at triage. In the routine phases with 33,261 individuals (45.8% pre, 54.2% post), 64% were women, and 84% were seen at triage. While HIV positivity yield between pre- and post-training observation phases was similar (10.9% (269/2470) and 11.1% (207/1865), respectively), we observed an increase in yield in the post-training routine phase for women in triage, rising from 4.8% (74/1553) to 7.3% (61/831) (Yield ratio = 1.54; 95%CI: 1.11-2.14). Age (25-49 years) (OR = 2.43; 95%CI: 1.37-4.33), working in industry/mining (OR = 4.94; 95%CI: 2.17-11.23), unawareness of partner's HIV status (OR = 2.50; 95%CI: 1.91-3.27), and visiting a healer (OR = 1.74; 95%CI: 1.03-2.93) were factors associated with a positive HIV test. Including these factors in the targeted PITC algorithm could have increased new HIV diagnoses by 2.6%. In conclusion, providing refresher training and adapting the current targeted PITC algorithm through further research can help reach undiagnosed PLHIV, treat all, and ultimately eliminate HIV, especially in resource-limited rural areas.
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Humanos , Masculino , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Consejo , Triaje/métodos , Técnicas y Procedimientos Diagnósticos/estadística & datos numéricos , Servicio de Urgencia en Hospital , Mozambique/epidemiologíaRESUMEN
OBJECTIVE: Evaluate the effect of three multimonth dispensing (3MMD) of antiretroviral therapy (ART) on HIV care retention in southern Mozambique. DESIGN: Retrospective cohort study. METHODS: We analyzed routine health data from people with HIV (PWH) aged 10 years old and older who started ART between January 2018 and March 2021. Individuals were followed until December 2021. Cox proportional-hazards models were used to compare attrition (lost to follow-up, death, and transfer out) between 3MMD and monthly ART dispensing. Results were stratified by time on ART before 3MMD enrolment: 'early enrollers' (<6âmonths on ART) and 'established enrollers' (≥6âmonths on ART), and age groups: adolescents and youth (AYLHIV) (10-24âyears) and adults (≥25âyears). RESULTS: We included 7378 PWH (25% AYLHIV, 75% adults), with 59% and 62% enrolled in 3MMD, respectively. Median follow-up time was 11.3 [interquartile range (IQR): 5.7-21.6] months for AYLHIV and 10.2 (IQR: 4.8-20.9) for adults. Attrition was lower in PWH enrolled in 3MMD compared with monthly ART dispensing, in both established (aHR AYLHIVâ=â0.65; 95% CI: 0.54-0.78 and aHR adultsâ=â0.50; 95% confidence interval (CI): 0.44-0.56) and early enrollers (aHR AYLHIVâ=â0.70; 95% CI: 0.58-0.85 and aHR adultsâ=â0.63; 95% CI: 0.57-0.70). Among individuals in 3MMD, male gender (aHRâ=â1.30; 95% CI: 1.18-1.44) and receiving care in a medium-volume/low-volume healthcare facility (aHRâ=â1.18; 95% CI: 1.03-1.34) increased attrition risk. Conversely, longer ART time before 3MMD enrolment (aHRâ=â0.93; 95% CI: 0.92-0.94 per 1 month increase) and age at least 45âyears (aHRâ=â0.77, 95% CI: 0.67-0.89) reduced risk of attrition. CONCLUSION: 3MMD improves retention in care compared with monthly dispensing among established and early enrollers, although to a lesser extent among the latter.
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Infecciones por VIH , Retención en el Cuidado , Humanos , Mozambique , Estudios Retrospectivos , Infecciones por VIH/tratamiento farmacológico , Masculino , Femenino , Adulto , Adolescente , Adulto Joven , Niño , Retención en el Cuidado/estadística & datos numéricos , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Persona de Mediana Edad , Antirretrovirales/uso terapéutico , Cumplimiento de la Medicación/estadística & datos numéricos , Perdida de SeguimientoRESUMEN
With the advent of antiretroviral therapy (ART), perinatal HIV infection is declining globally but prevalence in Sub-Saharan Africa is still greater than other nations. The relationship of HIV replication in early infancy and the developing immune system is not well understood. In this study, we investigated cellular components of the innate immune system including Natural Killer (NK) cells, monocytes, and Dendritic Cells (DC) in a cohort of HIV exposed infected (HEI) and age-matched HIV exposed uninfected (HEU) infants from Mozambique. Study entry was at the first visit after delivery at age 1-2 months for HIV diagnosis and initiation of ART. Phenotypic analysis by multi-parameter flow cytometry revealed an expansion of total NK cells and the dysfunctional, CD56-CD16+, NK cell subset; increased activation in monocytes and DC; and higher levels of inflammatory homing receptor CCR5 on circulating DC subsets in the HEI infants. NKG2A, an inhibitory receptor for NK cytolytic function, was reduced in HEI compared to HEU and positively correlated with pre-ART viral load (VL) while expression of CCR2, the inflammatory homing receptor, on NK was negatively correlated with VL. Other subsets exhibited positive correlations with VL including the frequency of intermediate monocytes amongst total monocytes. Longitudinal analysis of VL indicated suboptimal ART adherence in HEI. Regardless of level of viral suppression achieved, the frequencies of specific innate immune subsets in HEI were normalized to HEU by 18m. These data support the notion that in early life, NK cells play a role in virus control and should be explored for functional attributes that are effective against HIV at this time during development. Overall, our study provides high resolution overview of the innate immune system during perinatal HIV infection.
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BACKGROUND: Non-disclosure of known HIV status by people living with HIV but undergoing HIV testing leads to waste of HIV testing resources and distortion of estimates of HIV indicators. In Mozambique, an estimated one-third of persons who tested positive already knew their HIV-positive status. To our knowledge, this study is the first to assess the factors that prevent people living with HIV (PLHIV) from disclosing their HIV-positive status to healthcare providers during a provider-initiated counseling and testing (PICT) campaign. METHODS: This analysis was nested in a larger PICT cross-sectional study performed in the Manhiça District, Southern Mozambique from January to July 2019, in which healthcare providers actively asked patients about their HIV-status. Patients who tested positive for HIV were crosschecked with the hospital database to identify those who had previously tested positive and were currently or previously enrolled in care. PLHIV who did not disclose their HIV-positive status were invited to participate and provide consent, and were interviewed using a questionnaire designed to explore barriers, patterns of community/family disclosure, and stigma and discrimination. RESULTS: We found that 16.1% of participants who tested positive during a PICT session already knew their HIV-positive status but did not disclose it to the healthcare provider. All the participants reported previous mistreatment by general healthcare providers as a reason for nondisclosure during PICT. Other reasons included the desire to know if they were cured (33.3%) or to re-engage in care (23.5%). Among respondents, 83.9% reported having disclosed their HIV-status within their close community, 48.1% reported being victims of verbal or physical discrimination following their HIV diagnosis, and 46.7% reported that their HIV status affected their daily activities. CONCLUSION: Previous mistreatment by healthcare workers was the main barrier to disclosing HIV-positive status. The high proportion of those disclosing their HIV status to their community but not to healthcare providers suggests that challenges with patient-provider relationships affect this care behavior rather than social stigma and discrimination. Improving patient-provider relationships could increase trust in healthcare providers, reduce non-disclosures, and help optimize resources and provide accurate estimates of the UNAIDS first 95 goal.
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Infecciones por VIH , Personal de Salud , Humanos , Estudios Transversales , Mozambique/epidemiología , Bases de Datos Factuales , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiologíaRESUMEN
BACKGROUND: Despite antiretroviral treatment (ART), immune dysfunction persists in children with perinatal HIV infection (HEI). Here we investigated the impact of HIV status on maternal antibody (Ab) passage, long-term vaccine induced immunity and B-cell maturation. METHODS: 46 HIV Exposed Uninfected (HEU), 43 HEI, and 15 HIV unexposed uninfected (HUU) infants were vaccinated with 3 doses of DTaP-HepB-Hib-PCV10-OP at 2, 3, and 4 months at Matola Provincial Hospital, Maputo, Mozambique. Tetanus toxoid specific (TT) IgG, HIV Ab and B-cell phenotype characteristics were evaluated at entry, pre-ART, 5, 10, and 18 months in this longitudinal cohort study. FINDINGS: Baseline (maternal) plasma TT Ab levels were significantly lower in HEI compared to both HEU and HUU and a faster decay of TT Ab was observed in HEI compared to HEU with significantly lower TT Ab levels at 10 and 18 months of age. TT unprotected (UP) (≤0.1 IU/mL) HEI showed higher HIV-RNA at entry and higher longitudinal HIV viremia (Area Under the Curve) compared to TT protected (P) HEI. A distinct HIV-Ab profile was found at entry in HEI compared to HEU. B-cell phenotype showed a B-cell perturbation in HEI vs HEU infants at entry (mean age 40.8 days) with lower transitional CD10+CD19+ B-cells and IgD+CD27- naive B-cells and an overall higher frequency of IgD-CD27- double negative B-cell subsets in HEI. INTERPRETATION: B-cell perturbation, presenting with higher double negative IgD-CD27- B-cells was observed in neonatal age and may play a major role in the B-cell exhaustion in HEI. The ability to maintain TT protective Ab titers over time is impaired in HEI with uncontrolled viral replication and the current vaccination schedule is insufficient to provide long-term protection against tetanus. FUNDING: This work was supported by: NIH grant to SP (5R01AI127347-05); Children's Hospital Bambino Gesú (Ricerca corrente 2019) to NC, and Associazione Volontari Bambino Gesù to PP.
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Infecciones por VIH , Vacunas , Embarazo , Femenino , Humanos , Mozambique , Estudios Longitudinales , Anticuerpos/uso terapéutico , África , Antirretrovirales/uso terapéutico , VacunaciónRESUMEN
Despite antiretroviral treatment (ART), immune dysfunction persists in children with perinatal HIV infection (HEI). Here we investigated the impact of HIV status on maternal antibody (Ab) passage, long-term vaccine induced immunity and B-cell maturation. Methods: 46 HIV Exposed Uninfected (HEU), 43 HEI, and 15 HIV unexposed uninfected (HUU) infants were vaccinated with 3 doses of DTaP-HepB-Hib-PCV10-OP at 2, 3, and 4 months at Matola Provincial Hospital, Maputo, Mozambique. Tetanus toxoid specific (TT) IgG, HIV Ab and B-cell phenotype characteristics were evaluated at entry, pre-ART, 5, 10, and 18 months in this longitudinal cohort study. Findings: Baseline (maternal) plasma TT Ab levels were significantly lower in HEI compared to both HEU and HUU and a faster decay of TT Ab was observed in HEI compared to HEU with significantly lower TT Ab levels at 10 and 18 months of age. TT unprotected (UP) (≤0.1 IU/mL) HEI showed higher HIV-RNA at entry and higher longitudinal HIV viremia (Area Under the Curve) compared to TT protected (P) HEI. A distinct HIV-Ab profile was found at entry in HEI compared to HEU. B-cell phenotype showed a B-cell perturbation in HEI vs HEU infants at entry (mean age 40.8 days) with lower transitional CD10+CD19+ B-cells and IgD+CD27- naive B-cells and an overall higher frequency of IgD-CD27- double negative B-cell subsets in HEI. Interpretation: B-cell perturbation, presenting with higher double negative IgD-CD27- B-cells was observed in neonatal age and may play a major role in the B-cell exhaustion in HEI. The ability to maintain TT protective Ab titers over time is impaired in HEI with uncontrolled viral replication and the current vaccination schedule is insufficient to provide long-term protection against tetanus. Funding: This work was supported by: NIH grant to SP (5R01AI127347-05); Children's Hospital Bambino Gesú (Ricerca corrente 2019) to NC, and Associazione Volontari Bambino Gesù to PP.
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Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Antirretrovirales/uso terapéutico , Embarazo , MozambiqueRESUMEN
BACKGROUND: Loneliness in older people seems to have emerged as an increasingly prevalent social problem. OBJECTIVE: To apply a machine learning (ML) algorithm to the task of understanding the influence of sociodemographic variables, physical fitness, physical activity levels (PAL), and sedentary behavior (SB) on the loneliness feelings of physically trained older people. MATERIALS AND METHODS: The UCLA loneliness scale was used to evaluate loneliness, the Functional Fitness Test Battery was used to evaluate the correlation of sociodemographic variables, physical fitness, PAL, and SB in the loneliness feelings scores of 23 trained older people (19 women and 4 men). For this purpose, a naive Bayes ML algorithm was applied. RESULTS: After analysis, we inferred that aerobic fitness (AF), hand grip strength (HG), and upper limb strength (ULS) comprised the most relevant variables panel to cause high participant loneliness with 100% accuracy and F-1 score. CONCLUSIONS: The naive Bayes algorithm with leave-one-out cross-validation (LOOCV) predicted loneliness in trained older with a high precision. In addition, AF was the most potent variable in reducing loneliness risk.
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BACKGROUND: The persistence of HIV-1-infected cells during antiretroviral therapy is well documented but may be modulated by early initiation of antiretroviral therapy in infants. METHODS: Here, we longitudinally analyzed the proviral landscape in nine infants with vertical HIV-1 infection from Mozambique over a median period of 24 months, using single-genome, near full-length, next-generation proviral sequencing. RESULTS: We observed a rapid decline in the frequency of intact proviruses, leading to a disproportional under-representation of intact HIV-1 sequences within the total number of HIV-1 DNA sequences after 12-24 months of therapy. In addition, proviral integration site profiling in one infant demonstrated clonal expansion of infected cells harboring intact proviruses and indicated that viral rebound was associated with an integration site profile dominated by intact proviruses integrated into genic and accessible chromatin locations. CONCLUSION: Together, these results permit rare insight into the evolution of the HIV-1 reservoir in infants infected with HIV-1 and suggest that the rapid decline of intact proviruses, relative to defective proviruses, may be attributed to a higher vulnerability of genome-intact proviruses to antiviral immunity. Technologies to analyze combinations of intact proviral sequences and corresponding integration sites permit a high-resolution analysis of HIV-1 reservoir cells after early antiretroviral treatment initiation in infants.
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Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , Lactante , VIH-1/genética , Mozambique/epidemiología , ADN Viral/genética , Provirus/genética , Linfocitos T CD4-Positivos , Carga ViralRESUMEN
Psychosocial support (PSS) to caregivers of HIV-infected infants on antiretroviral treatment (ART) is crucial to ensure ART adherence and sustained long-term viral suppression in children. A specific approach including tools to monitor and understand adherence behavior and risk factors that prevent optimal treatment compliance are urgently needed. This qualitative exploratory study, conducted in southern Mozambique, monitored the infants' viral response trajectories during 18 months follow-up, as a measure of adherence, reviewed the caregiver's PSS session notes and the answers to a study questionnaire, to analyze whether the standard PSS checklist applied to infants' caregivers can identify barriers influencing their adherence. Only 9 of 31 infants had sustained virologic response. Reported factors affecting adherence were: difficulties in drugs administration, shared responsibility to administer treatment; disclosure of child's HIV status to family members but lack of engagement; mother's ART interruption and poor viral response. In conclusion, we found that the standard PSS approach alone, applied to caregivers, was lacking focus on many relevant matters that were identified by the study questionnaire. A comprehensive patient-centered PSS package of care, including an adherence risk factor monitoring tool, tailored to caregivers and their children must be developed.
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Fármacos Anti-VIH , Infecciones por VIH , Niño , Humanos , Lactante , Cuidadores/psicología , Cumplimiento de la Medicación/psicología , Mozambique , Infecciones por VIH/tratamiento farmacológico , Antirretrovirales/uso terapéutico , Fármacos Anti-VIH/uso terapéuticoRESUMEN
Possuir a capacidade de identificar as emoções e atribuir-lhes significado, é fundamental para a saúde mental dos adolescentes. Desta forma, facilitar o acesso às emoções e à sua expressão abre as portas à possibilidade dos adolescentes elaborarem as suas vivências, redifinirem significados e melhorarem a sua vida emocional, diminuindo os riscos para a sua saúde mental. Neste sentido, o projeto de investigação "Em busca das palavras Mediadores expressivos e expressão das emoções nos adolescentes" é um projeto de investigação acção com abordagem mista (qualitativa e quantitativa), que pretende desenvolver uma intervenção terapêutica com um grupo de adolescentes, com recursos aos mediadores expressivos como facilitadores do acesso às emoções e à sua expressão. A intervenção desenvolveu-se com um grupo terapêutico de 6 adolescentes, em contexto de Hospital de Dia, com idades compreendidas entre os 14 e os 18 anos, mediado por dois Enfermeiros Especialistas em Enfermagem de Saúde Mental e Psiquiátrica. Foram planeadas 11 atividades para serem realizadas em 12 sessões, com a duração de 90 minutos cada, com recurso ao desenho, à pintura e à modelagem como mediadores expressivos, tendo por base o modelo do Continuum das Terapias Expressivas de Hinz (2009). A recolha e análise dos dados envolveu a observação participante, com recurso a notas de campo. Foi também aplicada a Escala da Expressividade Emocional (Kring, Smith, & Neale, 1994), validada para a população portuguesa, aplicada em dois momentos antes do início do projeto e no final. A nível dos resultados, verificou-se que a utilização dos mediadores expressivos facilitou o acesso às emoções e a capacidade de expressão oral dos adolescentes, tendo melhorado a sua capacidade de exprimir as emoções e do reconhecimento destas pelo Outro.
Having the ability to identify emotions and attribute meaning to them is fundamental me adolescents' mental health. Thus, facilitating access to emotions and their expression opens the door to the possibility for adolescents to elaborate their experiences, redeem meanings and improve their emotional life, reducing the risks to their mental health. In this line of thought, the research project "Em busca das palavras Mediadores expressivos e expressão das emoções nos adolescentes", is an action-research project with a mixed approach (qualitative and quantitative), which aims to develop a therapeutic intervention for groups of adolescents, with resources to expressive mediators as facilitators of access to emotions and their expression. The intervention was developed with a therapeutic group of 6 adolescents, in the context of Day Hospital, aged between 14 and 18 years, mediated by two Specialist Nurses in Mental and Psychiatric Health Nursing. Eleven activities were planned for twelve sessions, lasting 90 minutes each, using drawing, painting and modeling as expressive mediators, based on the Hinz Expressive Therapies Continuum model (2009). Data collection and analysis involved participant observation using field notes. The Emotional Expressiveness Scale (Kring, Smith, & Neale, 1994) was also applied, validated for the Portuguese population, applied in two moments before the beginning of the project and at the end. As for the results, it was found that the use of expressive mediators facilitated access to emotions and the adolescents' ability of oral expression, which improved their ability to express emotions and their recognition by the Other.
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Adolescente , Arteterapia , Enfermería Psiquiátrica , Psicoterapia de GrupoRESUMEN
Early initiation of antiretroviral therapy and adherence to achieve viral load suppression (VLS) are crucial for reducing morbidity and mortality of perinatally HIV-infected infants. In this descriptive cohort study of 39 HIV perinatally infected infants, who started treatment at one month of life in Mozambique, we aimed to describe the viral response over 2 years of follow up. VLS ≤ 400 copies/mL, sustained VLS and viral rebound were described using a Kaplan-Meier estimator. Antiretroviral drug transmitted resistance was assessed for a sub-group of non-VLS infants. In total, 61% of infants reached VLS, and 50% had a rebound. Cumulative probability of VLS was 36%, 51%, and 69% at 6, 12 and 24 months of treatment, respectively. The median duration of VLS was 7.4 months (IQR 12.6) and the cumulative probability of rebound at 6 months was 30%. Two infants had resistance biomarkers to drugs included in their treatment regimen. Our findings point to a low rate of VLS and high rate of viral rebound. More frequent viral response monitoring is advisable to identify infants with rebound and offer timely adherence support. It is urgent to tailor the psychosocial support model of care to this specific age group and offer differentiated service delivery to mother-baby pairs.
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Logistic regression (LR) is the most common prediction model in medicine. In recent years, supervised machine learning (ML) methods have gained popularity. However, there are many concerns about ML utility for small sample sizes. In this study, we aim to compare the performance of 7 algorithms in the prediction of 1-year mortality and clinical progression to AIDS in a small cohort of infants living with HIV from South Africa and Mozambique. The data set (n = 100) was randomly split into 70% training and 30% validation set. Seven algorithms (LR, Random Forest (RF), Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Naïve Bayes (NB), Artificial Neural Network (ANN), and Elastic Net) were compared. The variables included as predictors were the same across the models including sociodemographic, virologic, immunologic, and maternal status features. For each of the models, a parameter tuning was performed to select the best-performing hyperparameters using 5 times repeated 10-fold cross-validation. A confusion-matrix was built to assess their accuracy, sensitivity, and specificity. RF ranked as the best algorithm in terms of accuracy (82,8%), sensitivity (78%), and AUC (0,73). Regarding specificity and sensitivity, RF showed better performance than the other algorithms in the external validation and the highest AUC. LR showed lower performance compared with RF, SVM, or KNN. The outcome of children living with perinatally acquired HIV can be predicted with considerable accuracy using ML algorithms. Better models would benefit less specialized staff in limited resources countries to improve prompt referral in case of high-risk clinical progression.
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Síndrome de Inmunodeficiencia Adquirida , Teorema de Bayes , Niño , Humanos , Modelos Logísticos , Aprendizaje Automático , Redes Neurales de la ComputaciónRESUMEN
BACKGROUND: The World Health Organization (WHO) risk assessment algorithm for vertical transmission of HIV (VT) assumes the availability of maternal viral load (VL) result at delivery and early viral control 4 weeks after initiating antiretroviral treatment (ART). However, in many low-and-middle-income countries, VL is often unavailable and mothers' ART adherence may be suboptimal. We evaluate the inclusion of the mothers' self-reported adherence into the established WHO-algorithm to identify infants eligible for enhanced post-natal prophylaxis when mothers' VL result is not available at delivery. METHODS: We used data from infants with perinatal HIV infection and their mothers enrolled from May-2018 to May-2020 in Mozambique, South Africa, and Mali. We retrospectively compared the performance of the WHO-algorithm with a modified algorithm which included mothers' adherence as an additional factor. Infants were considered at high risk if born from mothers without a VL result in the 4 weeks before delivery and with adherence <90%. RESULTS: At delivery, 143/184(78%) women with HIV knew their status and were on ART. Only 17(12%) obtained a VL result within 4 weeks before delivery, and 13/17(76%) of them had VL ≥1000 copies/ml. From 126 women on ART without a recent VL result, 99(79%) had been on ART for over 4 weeks. 45/99(45%) women reported suboptimal (< 90%) adherence. A total of 81/184(44%) infants were classified as high risk of VT as per the WHO-algorithm. The modified algorithm including self-adherence disclosure identified 126/184(68%) high risk infants. CONCLUSIONS: In the absence of a VL result, mothers' self-reported adherence at delivery increases the number of identified infants eligible to receive enhanced post-natal prophylaxis.
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Fármacos Anti-VIH , Infecciones por VIH , Complicaciones Infecciosas del Embarazo , Algoritmos , Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/uso terapéutico , Femenino , Infecciones por VIH/prevención & control , Humanos , Lactante , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Estudios Retrospectivos , Medición de Riesgo , Autoinforme , Organización Mundial de la SaludRESUMEN
The global market for dental implants is constantly evolving. To overcome the limitations of conventional strategies - invasive surgeries and bone loss around the implant-, new approaches, namely the development of CAD/CAM customized implants, are emerging as promising solutions for replacing missing teeth, thus avoiding destruction of bone by drilling it. Despite the efforts that are being carried out, the designing, including image acquisition, and manufacturing efficacy of such rehabilitation therapy is not easily found in the literature. In this sense, this research work aimed to assess the errors associated with the image acquisition, treatment and manufacturing of Customized Root-Analogue Implants (CRAI). The experimental procedure, carried out in a dog cadaveric mandible, encompassed the image acquisition and treatment and the subsequent manufacturing of four different CRAI. Two Image acquisition methods (CBCT and X-ray), and different software for their treatment were used, and the final CRAI were manufactured by Computer Numerical Control. Results revealed the CBCT scan allowed to properly visualize the original teeth contours. However, all the obtained teeth geometries presented smaller surface areas when compared to the original teeth indicating however a systematic predictable error. On the other hand, when comparing the surface area of the digital and the manufactured teeth, very small differences were observed, which indicates that the CNC manufacturing technique is a promising solution for such applications. When placing the produced CRAI in the dog mandible it was possible to observe a lack of congruency between the CRAI and bone, mainly due to image acquisition process errors and the destruction of the periodontal ligament during the soft tissues removal process. Thus, CBCT images seem to be a feasible route to design root-analogue implants, and, if needed, a compensation strategy for the systematic image acquisition error may be implemented.
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Implantes Dentales , Animales , Cadáver , Diseño Asistido por Computadora , Perros , Humanos , Mandíbula/diagnóstico por imagen , Mandíbula/cirugía , TecnologíaRESUMEN
INTRODUCTION: With growing attention globally to the childhood tuberculosis epidemic after decades of neglect, and with the burden of severe acute malnutrition (SAM) remaining unacceptably high worldwide, the collision of these two diseases is an important focus for improving child health. AREAS COVERED: This review describes the clinical and public health implications of the interplay between tuberculosis and SAM, particularly for children under the age of five, and identifies priority areas for improved programmatic implementation and future research. We reviewed the literature on PubMed and other evidence known to the authors published until August 2021 relevant to this topic. EXPERT OPINION: To achieve the World Health Organization's goal of eliminating deaths from childhood tuberculosis and to improve the abysmal outcomes for children with SAM, further research is needed to 1) better understand the epidemiologic connections between child tuberculosis and SAM, 2) improve case finding of tuberculosis in children with SAM, 3) assess unique treatment considerations for tuberculosis when children also have SAM, and 4) ensure tuberculosis and SAM are strongly addressed in decentralized, integrated models of providing primary healthcare to children.
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Desnutrición Aguda Severa , Tuberculosis , Niño , Salud Global , Humanos , Lactante , Desnutrición Aguda Severa/diagnóstico , Desnutrición Aguda Severa/epidemiología , Desnutrición Aguda Severa/terapia , Tuberculosis/diagnóstico , Tuberculosis/epidemiologíaRESUMEN
Zirconia is becoming reckoned as a promising solution for different applications, in particular those within the dental implant investigation field. It has been proved to successfully overcome important limitations of the commonly used titanium implants. The adhesion of microorganisms to the implants, in particular of bacteria, may govern the success or the failure of a dental implant, as the accumulation of bacteria on the peri-implant bone may rapidly evolve into periodontitis. However, bacterial adhesion on different zirconia architectures is still considerably unknown. Therefore, the adhesion of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa to zirconia surfaces with different finishings was evaluated and compared to a titanium surface. The adhesion interaction between S. aureus and P. aeruginosa was also evaluated using a co-culture since these bacteria are infamous due to their common presence in chronic wound infections. Results showed that different bacterium species possess different properties which influence their propensity to adhere to different roughness levels and architectures. E. coli revealed a higher propensity to adhere to zirconia channelled surfaces (7.15 × 106 CFU/mL), whereas S. aureus and P. aeruginosa adhered more to the titanium control group (1.07 × 105 CFU/mL and 8.43 × 106 CFU/mL, respectively). Moreover, the co-culture denoted significant differences on the adhesion behaviour of bacteria. Despite not having shown an especially better behaviour regarding bacterial adhesion, zirconia surfaces with micro-channels are expected to improve the vascularization around the implants and ultimately enhance osseointegration, thus being a promising solution for dental implants.
Asunto(s)
Implantes Dentales , Staphylococcus aureus , Técnicas de Cocultivo , Escherichia coli , Oseointegración , Propiedades de Superficie , Titanio , CirconioRESUMEN
BACKGROUND: The burden of HIV is especially concerning for Eastern and Southern Africa (ESA), as despite expansion of test-and-treat programmes, this region continues to experience significant challenges resulting from high rates of morbidity, mortality and new infections. Hard-won lessons from programmes on the ground in ESA should be shared. OBJECTIVES: This report summarises relevant evidence and regional experts' recommendations regarding challenges specific to ESA. METHOD: This commentary includes an in-depth review of relevant literature, progress against global goals and consensus opinion from experts. RESULTS: Recommendations include priorities for essential research (surveillance data collection, key and vulnerable population education and testing, in-country testing trials and evidence-based support services to improve retention in care) as well as research that can accelerate progress towards the prevention of new infections and achieving ambitious global goals in ESA. CONCLUSION: The elimination of HIV in ESA will require continued investment, commitment to evidence-based programmes and persistence. Local research is critical to ensuring that responses in ESA are targeted, efficient and evaluated.