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BACKGROUND: Adolescent girls and young women (AGYW) in sub-Saharan Africa face a disproportionately higher HIV/AIDS burden despite the global decline in incidence. Existing interventions often fail to adequately address their unique social, economic, and cultural challenges, limiting access to essential HIV/AIDS services, including HIV testing. Emerging evidence indicates that HIV self-testing, a user-friendly and confidential method, enhances HIV diagnosis and linkage to care by targeting these barriers. This study aims to assess the feasibility, acceptability, and preliminary impact of a peer-delivered, community-health worker (CHW)-facilitated HIV self-testing intervention for AGYW in Northern Uganda. METHODS: This mixed-methods quasi-experimental implementation science study will employ a three-fold approach. Firstly, we will conduct baseline formative qualitative research with 50 AGYW, 50 parents/partners to AGYW, 30 CHWs, 15 community leaders, and the district health office to inform the design of a peer-delivered CHW-facilitated HIV self-testing intervention tailored to AGYW's needs in Northern Uganda. Secondly, we will implement a mixed-methods pilot study to assess the intervention's feasibility and acceptability, involving 415 AGYW, 30 AGYW peer leaders, and 10 CHWs in selected parishes and villages in Omoro district, Northern Uganda. Lastly, we will evaluate the implementation outcomes and preliminary impact of the intervention on HIV self-testing rates and linkage to care by collecting and analyzing quantitative data pre- and post-intervention, laying the groundwork for a future robust randomized controlled trial. DISCUSSION: Our intervention combines CHWs and peer-led strategies to address the unique challenges of AGYW in Northern Uganda, leveraging community resilience and peer influence. Successful completion of this project will provide a scalable model to be evaluated in a randomized trial and replicated in similar contexts. TRIAL REGISTRATION NUMBER: PACTR202404851907736. Registered with the Pan-African Clinical Trials Registry on April 22, 2024.
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In utero/peripartum antiretroviral (IPA) drug exposure in human immunodeficiency virus (HIV)-exposed children has established benefit for prevention of HIV mother-to-child-transmission but its association with height-for-age by adolescence is unknown. Hence we quantify IPA-associated growth differences at 6 to 18 years old among children with perinatally acquired HIV (CPHIV) infection and children HIV exposed but uninfected (CHEU) relative to children HIV unexposed and uninfected (CHUU). Cohort study. Kampala, Uganda. Two hundred thirty eight community controls and 490 children of women living with HIV born between 2000 and 2011 in a community were enrolled at 6 to 18 years of age and followed every 6 months for 1 year. Height-for-age determined at enrollment, 6 and 12 months after enrollment using the World Health Organization reference. IPA exposure was retrospectively determined from medical records and categorized as: no IPA, single-dose nevirapine with/without zidovudine (sdNVPâ ±â AZT), sdNVPâ +â AZTâ +â lamivudine, or combination antiretroviral therapy (cART). Mean differences (ß) with 95% confidence intervals (CIs) in height-for-age over 12 months were evaluated according to IPA exposure for CPHIV and CHEU and relative to CHUU using longitudinal linear mixed effects models adjusted for caregiver factors (sex, age, education, functioning in caregiving role, and lifetime adversity) in Statistical Analysis Software (v.9.4). Regardless of IPA type, CPHIV grew worse than CHUU by school-age/adolescence (ßâ =â -0.30, 95% CI: -0.48, -0.11). Relative to CHUU height-for-age was similar for CHEU exposed to sdNVPâ ±â AZT (ßâ =â -0.16, 95% CI: -0.46, 0.14) and for CHEU exposed to sdNVPâ +â AZTâ +â lamivudine (ßâ =â 0.08, 95% CI: -0.20, 0.35). However, CHEU without any IPA exposure had lower height-for-age (ßâ =â -0.27, 95% CI: -0.52, -0.00) whereas CHEU with cART exposure had greater height-for-age (ßâ =â 0.41, 95% CI: 0.10, 0.71) in comparison with CHUU by 6 to 18 years old. Our findings suggest that CHEU may achieve height-for-age parity with CHUU by school-age and adolescent years- especially if provided benefit of effective cART in the peripartum period. However, CPHIV regardless of IPA exposure type and CHEU without IPA exposure remain at a disadvantage and will benefit from intervention to support their growth.
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Fármacos Anti-VIH , Infecciones por VIH , Complicaciones Infecciosas del Embarazo , Embarazo , Femenino , Adolescente , Humanos , Lactante , Niño , Lamivudine/uso terapéutico , Uganda , Periodo Periparto , Estudios de Cohortes , Estudios Retrospectivos , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Infecciones por VIH/prevención & control , Antirretrovirales/uso terapéutico , Zidovudina/uso terapéutico , Fármacos Anti-VIH/uso terapéuticoRESUMEN
Caregiver's and child's self-reported quality of life (QOL) was defined using standardized questionnaires in a sample (N = 277) of 6-10 years old HIV-infected, HIV-exposed uninfected, and HIV-unexposed uninfected children from Uganda. Psychosocial stress (acute stress and cumulative lifetime adversity) and physiologic stress (dysregulations across 13 biomarkers), perinatal HIV status, and their interaction were related to child QOL via general linear models. Lower child- and caregiver-reported psychosocial stress were dose-dependently associated with higher QOL (acute stress: mean difference coefficient b = 8.1-14.8, effect size [ES] = 0.46-0.83). Lower allostasis was dose-dependently associated with higher QOL (b = 6.1-9.7, ES = 0.34-0.54). Given low caregiver acute stress, QOL for HIV-infected was similar to HIV-uninfected children; however, given high caregiver acute stress, a QOL disadvantage (b = -7.8, 95% CI: -12.8, -2.8; ES = -0.73) was evident for HIV-infected versus uninfected children. Testing of caregiver stress reduction interventions is warranted to increase wellbeing in dependent children.
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Experiencias Adversas de la Infancia/psicología , Alostasis/fisiología , Infecciones por VIH/psicología , Transmisión Vertical de Enfermedad Infecciosa , Calidad de Vida/psicología , Trastornos de Estrés Traumático Agudo/psicología , Estrés Fisiológico/fisiología , Estrés Psicológico/psicología , Niño , Femenino , Humanos , Masculino , UgandaRESUMEN
Globally, 150,000 new paediatric human immunodeficiency virus type 1 (HIV-1) infections occurred in 2015. There remain complex challenges to the global elimination of paediatric HIV-1 infection. Thus, for the global community to achieve elimination of new paediatric HIV-1 infections, innovative approaches need to be explored. Immune-based approaches to prevention of mother-to-child transmission (MTCT) may help fill some of the remaining gaps and provide new opportunities to achieve an AIDS-free generation. Immune-based interventions to prevent MTCT of HIV-1 may include paediatric HIV vaccines and passive immunization approaches. Recent discoveries providing evidence of robust immune responses to HIV in infants open new and exciting prospects for paediatric HIV vaccines. Moreover, successful vaccination of infants has a different set of requirements than vaccination of adults and may be easier to achieve. Proof-of-concept has been established over the last two decades that passively administered HIV-1 Env-specific monoclonal antibody (mAbs) can prevent chimeric simian human immunodeficiency virus (SHIV) transmission to newborn nonhuman primates. There has been tremendous progress in isolating and characterizing broadly neutralizing antibodies to HIV, and clinical testing of these antibodies for treatment and prevention in both infants and adults is a major effort in the field. Immune-based interventions need to be actively explored as they can provide critically important tools to address persistent challenges in MTCT prevention. It is a pivotal time for the field with active discussions on the best strategy to further reduce HIV infection of infants and accomplish the World Health Organization Fast-Track 2030 goals to eliminate new paediatric HIV infections.
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Infecciones por VIH/prevención & control , VIH-1/fisiología , Enfermedades del Recién Nacido/prevención & control , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Vacunas contra el SIDA/administración & dosificación , Vacunas contra el SIDA/inmunología , Adolescente , Adulto , Animales , Anticuerpos Neutralizantes/inmunología , Niño , Femenino , Anticuerpos Anti-VIH/inmunología , Infecciones por VIH/inmunología , Infecciones por VIH/transmisión , VIH-1/inmunología , Humanos , Inmunización Pasiva , Lactante , Recién Nacido , Enfermedades del Recién Nacido/inmunología , Enfermedades del Recién Nacido/virología , Masculino , Vacunación , Adulto JovenRESUMEN
Globally, 150,000 new paediatric human immunodeficiency virus type 1 (HIV-1) infections occurred in 2015. There remain complex challenges to the global elimination of paediatric HIV-1 infection. Thus, for the global community to achieve elimination of new paediatric HIV-1 infections, innovative approaches need to be explored. Immune-based approaches to prevention of mother-to-child transmission (MTCT) may help fill some of the remaining gaps and provide new opportunities to achieve an AIDS-free generation. Immune-based interventions to prevent MTCT of HIV-1 may include paediatric HIV vaccines and passive immunization approaches. Recent discoveries providing evidence of robust immune responses to HIV in infants open new and exciting prospects for paediatric HIV vaccines. Moreover, successful vaccination of infants has a different set of requirements than vaccination of adults and may be easier to achieve. Proof-of-concept has been established over the last two decades that passively administered HIV-1 Env-specific monoclonal antibody (mAbs) can prevent chimeric simian human immunodeficiency virus (SHIV) transmission to newborn nonhuman primates. There has been tremendous progress in isolating and characterizing broadly neutralizing antibodies to HIV, and clinical testing of these antibodies for treatment and prevention in both infants and adults is a major effort in the field. Immune-based interventions need to be actively explored as they can provide critically important tools to address persistent challenges in MTCT prevention. It is a pivotal time for the field with active discussions on the best strategy to further reduce HIV infection of infants and accomplish the World Health Organization Fast-Track 2030 goals to eliminate new paediatric HIV infections.
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Humanos , Masculino , Femenino , Recién Nacido , Lactante , Niño , Adolescente , Adulto , Adulto Joven , Infecciones por VIH/prevención & control , VIH-1 , VIH-1/inmunología , Vacunas contra el SIDA/inmunología , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Anticuerpos Neutralizantes/inmunología , Infecciones/virología , Anticuerpos Anti-VIH , Anticuerpos Anti-VIH/inmunología , Infecciones por VIH , Infecciones por VIH/inmunología , Vacunas contra el SIDA/administración & dosificaciónRESUMEN
BACKGROUND: We determined prevalence of pertussis infection and its associated host and environmental factors to generate information that would guide strategies for disease control. METHODS: In a cross-sectional study, 449 children aged 3 months to 12 years with persistent cough lasting ≥14 days were enrolled and evaluated for pertussis using DNA polymerase chain reaction (PCR) and ELISA serology tests. RESULTS: Pertussis prevalence was 67 (15% (95% Confidence Interval (CI): 12-18)) and 81 (20% (95% CI: 16-24)) by PCR and ELISA, respectively among 449 participating children. The prevalence was highest in children with >59 months of age despite high vaccination coverage of 94% in this age group. Study demographic and clinical characteristics were similar between pertussis and non-pertussis cases. Of the 449 children, 133 (30%) had a coughing household member and 316 (70%) did not. Among 133 children that had a coughing household member, sex of child, sharing bed with a coughing household member and having a coughing individual in the neighborhood were factors associated with pertussis. Children that had shared a bed with a coughing household individual had seven-fold likelihood of having pertussis compared to children that did not (odds ratio (OR) 7.16 (95% CI: 1.24-41.44)). Among the 316 children that did not have a coughing household member, age <23 months, having or contact with a coughing individual in neighborhood, a residence with one room, and having a caretaker with >40 years of age were the factors associated with pertussis. Age <23months was three times more likely to be associated with pertussis compared to age 24-59 months (OR 2.97 (95% CI: 1.07-8.28)). CONCLUSION: Findings suggest high prevalence of pertussis among children with persistent cough at a health facility and it was marked in children >59 months of age, suggesting the possibility of waning immunity. The factors associated with pertussis varied by presence or absence of a coughing household member.
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Vacuna contra la Tos Ferina/administración & dosificación , Tos Ferina/epidemiología , Tos Ferina/transmisión , Factores de Edad , Bordetella pertussis/fisiología , Niño , Preescolar , Estudios Transversales , Composición Familiar , Femenino , Humanos , Lactante , Masculino , Oportunidad Relativa , Prevalencia , Uganda , Población Urbana , Tos Ferina/inmunología , Tos Ferina/prevención & controlRESUMEN
BACKGROUND: Candida species is the third commonest cause of sepsis among neonates. Colonization by Candida is a predictor for candidemia among preterm neonates. OBJECTIVES: To determine prevalence of early Candida colonization and early outcome among colonized preterm neonates admitted to Mulago hospital Special Care Unit. METHODS: A prospective observational cohort was conducted between December 2008 and April 2009. Preterm neonates aged >72 hours and less than one week were screened for Candida colonization of the groin, oral pharynx and rectum using CHROMagar. Colonized neonates were followed up for 14 days. Blood cultures were done for those with signs of septicaemia. The Fisher's exact tests and logistic regression were conducted for factors associated with colonization and mortality among colonized neonates. P values of < 0.05 were considered significant and confidence interval of 95% was used. RESULTS: Candida colonization occurred in 50/213 (23.5%) neonates. Gestational age ≤ 30 weeks was the only factor independently associated with colonization (p = 0.005). Of the colonized 14/46 (30.4%) died and 13/46 (28.3%) developed mucocutaneous candidiasis. No candidemia was identified. Multiple site colonization was independently associated with mortality (p=0.035). CONCLUSION: The consequence of high colonization observed in this study needs to be further elucidated in Uganda.
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Candida/aislamiento & purificación , Candidiasis/epidemiología , Portador Sano/epidemiología , Enfermedades del Prematuro/epidemiología , Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal , Candida/crecimiento & desarrollo , Candidiasis/diagnóstico , Candidiasis/microbiología , Candidiasis/transmisión , Portador Sano/microbiología , Portador Sano/transmisión , Femenino , Edad Gestacional , Hospitales de Enseñanza , Humanos , Recién Nacido , Enfermedades del Prematuro/microbiología , Masculino , Tamizaje Masivo , Estudios Prospectivos , Factores de Riesgo , Sepsis/terapia , Índice de Severidad de la Enfermedad , Uganda/epidemiologíaRESUMEN
The benefits of long-term antiretroviral therapy (ART) are recognized all over the world with infected children maturing into adults and HIV infection becoming a chronic illness. However, the improved survival is associated with serious metabolic complications, including lipodystrophy (LD), dyslipidemia, insulin resistance, lactic acidosis and bone loss. In addition, the dyslipidemia mainly seen with protease inhibitors may increase the risk of cardiovascular disease in adulthood and potentially in children as they mature into adults. Nucleoside reverse transcriptase inhibitors, particularly stavudine, zidovudine and didanosine are linked to development of LD and lactic acidosis. Perinatally infected children initiate ART early in life; they require lifelong therapy with multiple drug regimens leading to varying toxicities, all potentially impacting their quality of life. LD has a significant impact on the mental health of older children and adolescents leading to poor self-image, depression and subsequent poor adherence to therapy. Reduced bone mineral density (BMD) is reported in both adults and children on ART with the potential for children to develop more serious bone complications than adults due to their rapid growth spurts and puberty. The role of vitamin D in HIV-associated osteopenia and osteoporosis is not clear and needs further study. Most resource-limited settings are unable to monitor lipid profiles or BMD, exposing infected children and adolescents to on-going toxicities with unclear long-term consequences. Improved interventions are urgently needed to prevent and manage these metabolic complications. Longitudinal cohort studies in this area should remain a priority, particularly in resource-limited settings where the majority of infected children reside.
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Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Enfermedades Metabólicas/inducido químicamente , Enfermedades Metabólicas/epidemiología , Adolescente , Niño , Humanos , Enfermedades Metabólicas/patologíaRESUMEN
BACKGROUND: A high prevalence of tuberculosis (TB) in children presenting with severe pneumonia has previously been reported in South Africa. However, little is known about TB among children with pneumonia in Uganda and other resource limited countries. Moreover, TB is associated with high morbidity and mortality among such children. We conducted this study to establish the burden of pulmonary TB in children admitted with severe pneumonia in our setting. METHODS: A cross-sectional study was conducted at Mulago, a National Referral and teaching hospital in Uganda. Hospitalised children 2 months to 12 years of age with severe pneumonia based on WHO case definition were enrolledfrom February to June 2011. Children with a previous TB diagnosis or receiving anti-TB treatment were excluded. Each child was screened for TB using Tuberculin skin test, Chest X-ray, induced sputum samples and blood culture for mycobacterium. Sputum smears were examined using fluorescent microscopy, and cultured on both Lowenstein Jensen media (LJ) and Mycobacterial Growth Indicator Tubes (MGIT). RESULTS: Of the 270 children with severe pneumonia who were recruited over a 5-month period in 2011, the incidence ratio of pulmonary TB in children admitted with severe pneumonia was 18.9% (95% CI 14.6 - 23.9). The proportion of culture confirmed PTB was 6.3% (95% CI 3.8 - 9.7). Age group under 1 year and 1 to 5 years (OR 2.8 (95% CI 1.7 - 7.4) and OR 2.4 (95% CI 1.05 - 5.9) respectively) were more likely to be associated with pulmonary TB compared to those children over 5 years of age. A history of TB smear positive contact was associated with pulmonary TB (OR 3.0 (95% CI 1.3-6.5). CONCLUSIONS: We found a high burden of pulmonary TB in children admitted with severe pneumonia. These data highlight the need for TB screening in children admitted with severe pneumonia so as to improve TB case finding and child survival.
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Costo de Enfermedad , Neumonía/complicaciones , Tuberculosis Pulmonar/complicaciones , Niño , Preescolar , Estudios Transversales , Hospitalización , Humanos , Incidencia , Lactante , Modelos Logísticos , Análisis Multivariante , Neumonía/terapia , Índice de Severidad de la Enfermedad , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/epidemiología , UgandaRESUMEN
BACKGROUND: Smear microscopy, a mainstay of tuberculosis (TB) diagnosis in developing countries, cannot differentiate M. tuberculosis complex from NTM infection, while pulmonary TB shares clinical signs with NTM disease, causing clinical and diagnostic dilemmas. This study used molecular assays to identify species and assess genotypic diversity of non-tuberculous mycobacteria (NTM) isolates from children investigated for pulmonary tuberculosis at a demographic surveillance site in rural eastern Uganda. METHODS: Children were investigated for pulmonary tuberculosis as part of a TB vaccine surveillance program (2009-2011). Two cohorts of 2500 BCG vaccinated infants and 7000 adolescents (12-18 years) were recruited and followed up for one to two years to determine incidence of tuberculosis. Induced sputum and gastric aspirates were processed by the standard N-acetyl L-cysteine (NALC)-NaOH method. Sediments were cultured in the automated MGIT (Becton Dickson) liquid culture system and incubated at 37°C for at least six weeks. Capilia TB assay was used to classify mycobacteria into MTC and NTM. The GenoType CM/AS assays were performed to identify species while Enterobacterial Repetitive Intergenic Consensus (ERIC) PCR genotyping was used to assess genetic diversity of the strains within each species. RESULTS: Among 2859 infants and 2988 adolescents screened, the numbers of TB suspects were 710 and 1490 infants and adolescents respectively. The prevalence of NTM in infant suspects was 3.7% (26/710) (95% CI 2.5-5.2) while that in adolescent suspects was 4.6% (69/1490) (95% CI 3.6-5.8). On culture, 127 isolates were obtained, 103 of which were confirmed as mycobacteria comprising of 95 NTM and eight M. tuberculosis complex. The Genotype CM/AS assay identified 63 of the 95 NTM isolates while 32 remained un-identified. The identified NTM species were M. fortuitum (40 isolates, 63.5%), M. szulgai (9 isolates, 14.3%), M. gordonae (6 isolates, 9.5%), M. intracellulare (3 isolates, 4.7%), M. scrofulaceum (2 isolates, 3.2%), M. lentiflavum (2 isolates, 3.2%), and M. peregrinum (1 isolate, 1.6%). Genotyping did not reveal any clustering in M. intracellulare, M. gordonae and M. szulgai species. M. fortuitum, on the other hand, had two clusters, one with three isolates of M. fortuitum 1 and the other with two isolates of M. fortuitum 2 subspecies. The remaining 35 of the 40 isolates of M. fortuitum had unique fingerprint patterns. CONCLUSION: M. fortuitum is the most common cause of infection by NTM among Infants and adolescents in rural Uganda. There is a varied number of species and genotypes, with minimal clustering within species, suggesting ubiquitous sources of infection to individuals in this community.
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Micobacterias no Tuberculosas/clasificación , Tuberculosis Pulmonar/microbiología , Adolescente , Vacuna BCG/administración & dosificación , Técnicas de Tipificación Bacteriana , Estudios de Cohortes , Estudios de Seguimiento , Jugo Gástrico/microbiología , Genotipo , Humanos , Lactante , Micobacterias no Tuberculosas/genética , Micobacterias no Tuberculosas/aislamiento & purificación , Filogenia , Reacción en Cadena de la Polimerasa , Prevalencia , Población Rural , Especificidad de la Especie , Esputo/microbiología , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/prevención & control , Uganda/epidemiologíaRESUMEN
OBJECTIVE: Nevirapine and cotrimoxazole are associated with hematologic toxicities and skin-rash. Safety of their concurrent use for prophylaxis over extended periods among HIV-exposed uninfected infants has not been previously assessed. DESIGN: Secondary data analysis of the 'HIV Prevention Trials Network-046 protocol' (version 2.0), a phase-III, randomized, placebo-controlled trial that assessed efficacy and safety of nevirapine prophylaxis against breast milk transmission of HIV-1. METHODS: Trial infants received 6-month study nevirapine/placebo, and standard-of-care peripartum single-dose nevirapine+/- zidovudine 'tail', and cotrimoxazole prophylaxis from 6 weeks through breastfeeding cessation. Adverse events were monitored using United States Division of AIDS Toxicity Tables (2004). Risk of neutropenia, anemia and skin-rash in the cotrimoxazoleâ+ânevirapine and the cotrimoxazoleâ+âplacebo groups were compared using negative-binomial regression. RESULTS: Incidence of neutropenia and/or anemia, and skin-rash was highest during the first 6 weeks of life and declined, thereafter, regardless of study group. Time to first adverse event after 6 weeks was similar in cotrimoxazoleâ+ânevirapine and cotrimoxazoleâ+âplacebo groups: hazard ratio (95% confidence interval) was 1.26 (0.96-1.66) for neutropenia and/or anemia (all grades), 1.27 (0.80-2.03) for neutropenia and/or anemia (grade ≥3) and 1.16 (0.46-2.90) for skin-rash (grade ≥2). There were no statistically significant differences in immediate (6 weeks-6 months) and long-term (6-12 months) adverse event risk among infants on cotrimoxazoleâ+ânevirapine versus cotrimoxazoleâ+âplacebo. CONCLUSION: Extended nevirapine and cotrimoxazole prophylaxis through 6 months of age among HIV-exposed uninfected infants did not appear to increase the immediate or long-term risk of neutropenia, anemia or skin-rash. Concurrent use beyond 6 months, however, needs to be evaluated.
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Anemia/inducido químicamente , Fármacos Anti-VIH/administración & dosificación , Exantema/inducido químicamente , Seropositividad para VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Neutropenia/inducido químicamente , Nevirapina/administración & dosificación , Combinación Trimetoprim y Sulfametoxazol/administración & dosificación , Adulto , Fármacos Anti-VIH/efectos adversos , Western Blotting , Lactancia Materna/efectos adversos , Esquema de Medicación , Erupciones por Medicamentos/etiología , Femenino , Seropositividad para VIH/epidemiología , Seropositividad para VIH/transmisión , Humanos , Lactante , Recién Nacido , Masculino , Leche Humana/virología , Nevirapina/efectos adversos , Embarazo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Combinación Trimetoprim y Sulfametoxazol/efectos adversos , Uganda/epidemiologíaRESUMEN
More than 2 million children globally are living with HIV infection and >90% of these reside in sub-Saharan Africa. Severe acute malnutrition (SAM) remains a major problem for HIV-infected children who live in resource-limited settings (RLS), and SAM is an important risk factor for mortality. SAM in HIV-infected children is associated with complications including electrolyte disorders, micronutrient deficiencies, and severe infections, which contribute to the high mortality. Access to antiretroviral therapy (ART) has significantly improved the survival of HIV-infected children, although the response to ART of children with SAM remains undocumented in the literature. Immune and virologic responses to ART in RLS are similar to those of infected children in resource-rich settings, but delays in initiation of therapy have led to a high early mortality. Antiretroviral drug toxicities have been described in children who receive therapy and may affect their quality of life and long-term survival. Metabolic complications of ART include lipodystrophy, dyslipidemia, lactic acidosis, insulin resistance, and osteopenia. These complications have been well described in adults and children from developed countries, but data from RLS are limited, and these complications may be compounded by SAM. In this article we review the epidemiology, clinical presentation, and complications of SAM in HIV-infected children and the metabolic complications of HIV-infected children in the era of ART, and discuss future research priorities for RLS.
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Fármacos Anti-VIH/uso terapéutico , Manejo de la Enfermedad , Infecciones por VIH/complicaciones , Enfermedades Metabólicas/etiología , Estado Nutricional , Pobreza , Desnutrición Proteico-Calórica/complicaciones , África del Sur del Sahara/epidemiología , Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/mortalidad , Recursos en Salud , Humanos , Desnutrición Proteico-Calórica/epidemiologíaRESUMEN
BACKGROUND: Scale up of paediatric antiretroviral therapy in resource limited settings continues despite limited access to routine laboratory monitoring. We documented the weight and height responses in HIV infected Ugandan children on highly active antiretroviral therapy and determined clinical factors associated with successful treatment outcomes. METHODS: A prospective cohort of HIV infected children were initiated on HAART and followed for 48 weeks. Body mass index for age z scores(BAZ), weight and height-for-age z scores (WAZ & HAZ) were calculated: CD4 cell % and HIV-1 RNA were measured at baseline and every 12 weeks. Treatment outcomes were classified according to; both virological and immunological success (VS/IS), virological failure and immunological success (VF/IS). virological success and immunological failure (VS/IF) and both virological and immunological failure (VF/IF). RESULTS: From March 2004 until May 2006, 124 HIV infected children were initiated on HAART. The median age (IQR) was 5.0 years (2.1 - 7.0) and 49% (61/124) were female. The median [95% confidence interval (CI)] BAZ, WAZ and HAZ at baseline were 0.29 (-2.9, -1.2), -1.2 (-2.1, -0.5) and -2.06 (-2.9, -1.2) respectively. Baseline median CD4 cell % and log10 HIV-1 RNA were; 11.8% (7.5-18.0) and 5.6 (5.2-5.8) copies/ml. By 48 weeks, mean WAZ and HAZ in the VF/IS group, which was younger, increased from - 0.98 (SD 1.7) to + 1.22 (SD 1.2) and from -1.99 (1.7) to + 0.76 (2.4) respectively. Mean increase in WAZ and HAZ in the VS/IF group, an older group was modest, from -1.84 (1.3) to - 0.41 (1.2) and -2.25 (1.2) to -1.16 (1.3) respectively. Baseline CD4 cell % [OR 6.97 95% CI (2.6 -18.6)], age [OR 4.6 95% CI (1.14 -19.1)] and WHO clinical stage [OR 3.5 95%CI (1.05 -12.7)] were associated with successful treatment outcome. CONCLUSIONS: HIV infected Ugandan children demonstrated a robust increase in height and weight z scores during the first 48 weeks of HAART, including those who failed to completely suppress virus. Older children initiating HAART with severe immune suppression were less likely to achieve a successful treatment outcome. These data emphasize the importance of initiating HAART early to ensure adequate immune and growth responses.
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Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Crecimiento , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Carga Viral , Niño , Preescolar , Estudios de Cohortes , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/fisiopatología , Humanos , Masculino , ARN Viral/análisis , Resultado del Tratamiento , UgandaRESUMEN
OBJECTIVES: To determine normal hematologic and selected blood chemistry values among healthy, full-term, non-HIV-exposed infants in Uganda and Malawi, and to determine the proportion of healthy babies with an apparent laboratory toxicity based on Division of AIDS toxicity tables. DESIGN: This was a cross-sectional laboratory study of infants from birth to 6 months of age. METHODS: Blood samples were collected from a total of 561 infants and analyzed according to age categories similar to those in the 2004 Division of AIDS toxicity tables. Select chemistry and hematology parameters were determined and values compared with those in the toxicity tables. RESULTS: In the first 56 days of life, there were few graded toxicities except for neutropenia in 2 of 10 (20%) Ugandan and 13 of 45 (29%) Malawian infants at birth. After 7 days, about 20% of the infants in Uganda and Malawi would have been classified as having a neutropenia whereas 47% and 53% of those more than 2 months of age in Uganda and Malawi respectively, would have been reported as having an abnormal hemoglobin. Chemistry findings were not different from US norms. CONCLUSIONS: These findings underscore the importance of establishing relevant local laboratory norms for infants.
Asunto(s)
Análisis Químico de la Sangre , Infecciones por VIH/epidemiología , Infecciones por VIH/patología , Estudios Transversales , Femenino , Pruebas Hematológicas/métodos , Humanos , Lactante , Recién Nacido , Malaui/epidemiología , Masculino , Uganda/epidemiología , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: To compare the response to a nevirapine (NVP)-based highly active antiretroviral therapy (HAART) in HIV-infected Ugandan children, exposed and nonexposed to single-dose NVP (sd NVP) at birth. METHODS: HIV-infected study children were initiated on stavudine/lamivudine/NVP as a fixed dose combination. CD4 cell percent and HIV-1 RNA were documented at baseline, 12, 24, 36, and 48 weeks post-initiation of HAART. RESULTS: Ninety-two children were enrolled in the study, 44 in the sd NVP-exposed and 48 in the nonexposed cohort. The median age at enrollment was 1.7 years [interquartile range (IQR) 1.2-2.4] and 7.8 years (IQR 5.9-9.2) in the sd NVP-exposed and nonexposed cohorts,respectively (P < 0.001). At baseline and week 48 post-HAART, the median CD4 cell percentages were 14% and 33% for the NVP-exposed group and 8% and 22.5% in the nonexposed group (P < 0.0001). The median (IQR) viral load at baseline was 650,568 (359,979-2,086,613) RNA copies/mL and 239,027 (105,904-494,813) RNA copies/mL in the NVP-exposed and nonexposed cohorts, respectively. After 48 weeks of HAART, 76% of the NVP-exposed and 80% of the nonexposed children had a median viral load of < 400 copies/mL (P = 0.74). CONCLUSIONS: Both HIV-infected Ugandan older infants and children that were exposed and not exposed to sd NVP at birth had favorable treatment outcomes on NVP-containing HAART.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Nevirapina/uso terapéutico , Adolescente , Terapia Antirretroviral Altamente Activa , Preescolar , Estudios de Cohortes , Femenino , Infecciones por VIH/prevención & control , Humanos , Lactante , Masculino , Resultado del Tratamiento , UgandaRESUMEN
OBJECTIVE: To determine the predictors for early versus later (breastfeeding) transmission of HIV-1. METHODS: Secondary data analysis was performed on HIV Network for Prevention Trials 012, a completed randomized clinical trial assessing the relative efficacy of nevirapine (NVP) versus zidovudine in reducing mother-to-child transmission (MTCT) of HIV-1. We used Cox regression analysis to assess risk factors for MTCT. The ViroSeq HIV genotyping and a sensitive point mutation assay were used to detect NVP resistance mutations. RESULTS: In this subset analyses, 122 of 610 infants were HIV infected, of whom 99 (81.1%) were infected early (first positive polymerase chain reaction < or =56 days). Incidence of MTCT after 56 days was low [0.7% per month (95% confidence interval, CI: 0.4 to 1.0)], but continued through 18 months. In multivariate analyses, early MTCT "factors" included NVP versus zidovudine (hazard ratio (HR) = 0.57, 95% CI: 0.38 to 0.86), pre-entry maternal viral load (VL, HR = 1.76, 95% CI: 1.28 to 2.41), and CD4 cell count (HR = 1.16, 95% CI: 1.05 to 1.28). Maternal VL (6-8 weeks) was associated with late MTCT (HR = 3.66, 95% CI: 1.78 to 7.50), whereas maternal NVP resistance (6-8 weeks) was not. CONCLUSIONS: Maternal VL was the best predictor of both early and late transmission. Maternal NVP resistance at 6-8 weeks did not predict late transmission.
Asunto(s)
Lactancia Materna , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , VIH-1/aislamiento & purificación , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/epidemiología , Fármacos Anti-VIH/uso terapéutico , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Humanos , Recién Nacido , Análisis Multivariante , Nevirapina/uso terapéutico , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/prevención & control , Complicaciones Infecciosas del Embarazo/virología , Modelos de Riesgos Proporcionales , Uganda/epidemiología , Carga Viral , Zidovudina/uso terapéuticoRESUMEN
OBJECTIVES: To determine the utility of total lymphocyte count (TLC) in predicting the 12-month mortality in HIV-infected Ugandan children and to correlate TLC and CD4 cell %. DESIGN: This is a retrospective data analysis of clinical and laboratory data collected prospectively on 128 HIV-infected children in the HIV Network for Prevention Trials 012 trial. METHODS: TLC and CD4 cell % measurements were obtained at birth, 14 weeks, and 12, 24, 36, 48, and 60 months of age and assessed with respect to risk of death within 12 months. RESULTS: Median TLC per microliter (CD4 cell %) was 4150 (41%) at birth, 4900 (24%) at 12 months, 4300 (19%) at 24 months, 4150 (19%) at 36 months, 4100 (18%) at 48 months, and 3800 (20%) at 60 months. The highest risk of mortality within 12 months was 34% - 37% at birth and declined to 13%-15% at 24 months regardless of TLC measurement. The correlation between CD4 cell % and TLC was extremely low overall (r = 0.01). CONCLUSIONS: The TLC did not predict a risk of progression to death within 12 months in HIV-infected Ugandan children. Therefore, TLC alone may not be a useful surrogate marker for determining those children at highest risk of death, who require antiretroviral therapy most urgently.