RESUMO
Human immunodeficiency virus (HIV) can adapt to an individual's T cell immune response via genomic mutations that affect antigen recognition and impact disease outcome. These viral adaptations are specific to the host's human leucocyte antigen (HLA) alleles, as these molecules determine which peptides are presented to T cells. As HLA molecules are highly polymorphic at the population level, horizontal transmission events are most commonly between HLA-mismatched donor/recipient pairs, representing new immune selection environments for the transmitted virus. In this study, we utilised a deep sequencing approach to determine the HIV quasispecies in 26 mother-to-child transmission pairs where the potential for founder viruses to be pre-adapted is high due to the pairs being haplo-identical at HLA loci. This scenario allowed the assessment of specific HIV adaptations following transmission in either a non-selective immune environment, due to recipient HLA mismatched to original selecting HLA, or a selective immune environment, mediated by matched donor/recipient HLA. We show that the pattern of reversion or fixation of HIV adaptations following transmission provides insight into the replicative cost, and likely compensatory networks, associated with specific adaptations in vivo. Furthermore, although transmitted viruses were commonly heavily pre-adapted to the child's HLA genotype, we found evidence of de novo post-transmission adaptation, representing new epitopes targeted by the child's T cell response. High-resolution analysis of HIV adaptation is relevant when considering vaccine and cure strategies for individuals exposed to adapted viruses via transmission or reactivated from reservoirs.
Assuntos
Adaptação Biológica/genética , Infecções por HIV/genética , HIV-1/genética , Transmissão Vertical de Doenças Infecciosas , Adaptação Biológica/imunologia , Adulto , Criança , Pré-Escolar , Evolução Molecular , Feminino , Infecções por HIV/imunologia , Infecções por HIV/transmissão , HIV-1/imunologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Pessoa de Meia-IdadeRESUMO
STUDY OBJECTIVES: Sleep-disordered breathing (SDB) is common in patients with neuromuscular disorders (NMD), developing before chronic hypercapnia appears. Polysomnography (PSG) is the diagnostic gold standard but is often impractical and poorly accessible for individuals with NMD. We sought to determine the diagnostic accuracy, feasibility, and patient preference of home sleep apnea testing (HSAT) compared with PSG for the detection of SDB in NMD. METHODS: Participants with NMD at risk for SDB aged ≥ 13 years underwent HSAT followed by overnight PSG with concomitant laboratory sleep apnea testing (same device as HSAT). Sensitivity and specificity were calculated for standard apnea-hypopnea index cutoffs for mild (≥ 5 events/h), moderate (≥ 15 events/h), and severe SDB (≥ 30 events/h) and for an oxygen desaturation index ≥ 5 events/h. Receiver operating characteristic curves were built. A questionnaire assessed patient preference. RESULTS: Of 38 participants, 73% had moderate to severe SDB and 79% had technically acceptable HSAT. For an apnea-hypopnea index ≥ 15 events/h, HSAT sensitivity and specificity were 50% and 88%, respectively. For an oxygen desaturation index ≥ 5 events/h, HSAT sensitivity and specificity were 95% and 78%, respectively. The area under the receiver operating characteristic curve for an apnea-hypopnea index ≥ 15 events/h was 0.88 (95% confidence interval, 0.69-1.00) for HSAT. The HSAT underestimated the apnea-hypopnea index from PSG (bias, -10.7 ± 15.9 events/h). HSAT was preferred to PSG by 61% of participants. CONCLUSIONS: HSAT is feasible, preferred by patients, and reliable for detecting SDB in most patients, although it cannot definitively rule out SDB. Therefore, HSAT is a viable diagnostic approach for SDB in NMD when PSG is not feasible, recognizing that it does not accurately distinguish between upper-airway obstruction and hypoventilation. Additional work is needed to further optimize home sleep testing in NMD. CITATION: Westenberg JN, Petrof BJ, Noel F, et al. Validation of home portable monitoring for the diagnosis of sleep-disordered breathing in adolescents and adults with neuromuscular disorders. J Clin Sleep Med. 2021;17(8):1579-1590.
Assuntos
Doenças Neuromusculares , Síndromes da Apneia do Sono , Adolescente , Adulto , Humanos , Hipoventilação , Doenças Neuromusculares/complicações , Doenças Neuromusculares/diagnóstico , Polissonografia , Sono , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/diagnósticoRESUMO
Expression of HLA-B57 is associated with restricted replication of human immunodeficiency virus (HIV), but the mechanism for its protective effect remains unknown. If this advantage depends upon CD8 T-cell recognition of B57-restricted epitopes, mother-to-child transmission of escape mutations within these epitopes could nullify its protective effect. However, if the B57 advantage is largely mediated by selection for fitness-attenuating viral mutations within B57-restricted epitopes, such as T242N in TW10-Gag, then the transmission of such mutations could facilitate viral control in the haploidentical infant. We assessed the consequences of B57-associated mutations on replication capacity, viral control, and clinical outcome after vertical transmission in 13 mother-child pairs. We found that expression of HLA-B57 was associated with exceptional control of HIV during infancy, even when mutations within TW10 and most other B57-restricted epitopes were transmitted, subverting the natural immunodominance of HLA-B57. In contrast, most B57-negative infants born to B57-positive mothers progressed rapidly to AIDS. The presence of T242N led to a reproducible reduction in viral fitness, as demonstrated by in vitro assays using NL4-3 constructs encoding p24 sequences from individual mothers and infants. Associated compensatory mutations within p24-Gag were observed to reverse this impairment and to influence the propensity of T242N to revert after transmission to B57-negative hosts. Moreover, primary failure to control viremia was observed in one infant to whom multiple compensatory mutations were transmitted along with T242N. These parallel in vivo and in vitro data suggest that HLA-B57 confers its advantage primarily by driving and maintaining a fitness-attenuating mutation in p24-Gag.
Assuntos
Proteína do Núcleo p24 do HIV/imunologia , Infecções por HIV/imunologia , HIV/crescimento & desenvolvimento , HIV/imunologia , Antígenos HLA-B/imunologia , Transmissão Vertical de Doenças Infecciosas , Mutação de Sentido Incorreto/imunologia , Sequência de Aminoácidos , Animais , Pré-Escolar , Progressão da Doença , Feminino , HIV/genética , Proteína do Núcleo p24 do HIV/genética , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Análise de Sequência de DNARESUMO
BACKGROUND: The one-year survival rate of adults and children with the acquired immunodeficiency syndrome (AIDS), without antiretroviral therapy, has been about 30 percent in Haiti. Antiretroviral therapy has recently become available in Haiti and in other developing countries. Data on the efficacy of antiretroviral therapy in developing countries are limited. High rates of coinfection with tropical diseases and tuberculosis, along with malnutrition and limited laboratory monitoring of therapy, may decrease the efficacy of antiretroviral therapy in these countries. METHODS: We studied the efficacy of antiretroviral therapy in the first 1004 consecutive patients with AIDS and without previous antiretroviral therapy who were treated beginning in March 2003 in Port-au-Prince, Haiti. RESULTS: During a 14-month period, three-drug antiretroviral therapy was initiated in 1004 patients, including 94 children under 13 years of age. At enrollment, the median CD4 T-cell count in adults and adolescents was 131 per cubic millimeter (interquartile range, 55 to 211 per cubic millimeter); in children, a median of 13 percent of T cells were CD4-positive (interquartile range, 8 to 20 percent). According to a Kaplan-Meier survival analysis, 87 percent of adults and adolescents and 98 percent of children were alive one year after beginning treatment. In a subgroup of 100 adult and adolescent patients who were followed for 48 to 56 weeks, 76 patients had fewer than 400 copies of human immunodeficiency virus RNA per milliliter. In adults and adolescents, the median increase in the CD4 T-cell count from baseline to 12 months was 163 per cubic millimeter (interquartile range, 77 to 251 per cubic millimeter). In children, the median percentage of CD4 T cells rose from 13 percent at baseline to 26 percent (interquartile range, 22 to 36 percent) at 12 months. Treatment-limiting toxic effects occurred in 102 of the 910 adults and adolescents (11 percent) and 5 of the 94 children (5 percent). CONCLUSIONS: This report documents the feasibility of effective antiretroviral therapy in a large number of patients in an impoverished country. Overall, the outcomes are similar to those in the United States. These results provide evidence in support of international efforts to make antiretroviral therapy available to patients with AIDS in developing countries.
Assuntos
Síndrome da Imunodeficiência Adquirida/terapia , Antirretrovirais/uso terapêutico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/mortalidade , Adolescente , Adulto , Antirretrovirais/efeitos adversos , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Estudos de Coortes , Países em Desenvolvimento , Feminino , HIV/genética , HIV/isolamento & purificação , Haiti/epidemiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Análise de Sobrevida , Resultado do Tratamento , Tuberculose/complicações , Tuberculose/tratamento farmacológicoRESUMO
OBJECTIVE: To assess outcomes after antiretroviral therapy (ART) in adolescents and youth in Haiti, a country with a generalized epidemic of infection with HIV-1. METHODS: An assessment was made of survival, plasma HIV-1 ribonucleic acid (RNA) concentrations and HIV-1 drug resistance patterns after 12 months of ART in patients aged 13-25 years who presented to a clinic in Port-au-Prince, Haiti, with AIDS between 1 March 2003 and 31 December 2005. Participants received ART in accordance with WHO guidelines. Kaplan-Meier analysis was used to estimate survival probabilities and their 95% confidence intervals (CI) for the period from ART initiation to death. FINDINGS: Of a total of 146 patients, 96 (66%) were female; the median CD4+ T-cell count at baseline was 129 cells/ml. By Kaplan-Meier analysis, 13% of the patients had died at 12 months, 17% at 24 months and 20% at 36 months. A plasma HIV-1 RNA concentration > or = 50 copies/ml was seen in 40 (51%) of 79 patients 12 months after treatment initiation and was associated with poor ART adherence. Among 29 patients with > 1000 copies/ml at 12 months, resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs) were detected in 23 cases (79%); to both NNRTIs and lamivudine in 21 (72%) cases; and to NNRTIs, lamivudine and other nucleoside reverse transcriptase inhibitors in 10 (35%) cases. One hundred and six participants (73%) reported sexual intercourse without condoms, and 35 of the 96 women (36%) were pregnant during follow-up. CONCLUSION: Adolescents and youth with AIDS receiving ART are at risk of virologic failure and disease progression and can therefore transmit HIV-1 to sexual partners and infants. Strategies to target the special needs of this age group are urgently needed.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral Múltipla/genética , Infecções por HIV/epidemiologia , HIV-1/genética , RNA/genética , Adolescente , Adulto , Farmacorresistência Viral Múltipla/efeitos dos fármacos , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Haiti/epidemiologia , Humanos , Masculino , Estudos Prospectivos , Inquéritos e Questionários , Análise de Sobrevida , Adulto JovemRESUMO
BACKGROUND: The ability to accurately determine respiratory muscle strength is vitally important in patients with neuromuscular disorders (NMD). Sniff nasal inspiratory pressure (SNIP), a test of inspiratory muscle strength, is easier to perform for many NMD patients than the more commonly used determination of maximum inspiratory pressure measured at the mouth (MIP). However, due to an inconsistent approach in the literature, the optimal technique to perform the SNIP maneuver is unclear. Therefore, we systematically evaluated the impact of performing the maneuver with nostril contralateral to the pressure-sensing probe open (SNIPOP) versus closed (SNIPCL), on determination of inspiratory muscle strength in NMD patients as well as control subjects with normal respiratory muscle function. METHODS: NMD patients (n = 52) and control subjects without respiratory dysfunction (n = 52) were studied. SNIPOP, SNIPCL, and MIP were measured during the same session and compared using ANOVA. Agreement and bias were assessed with intraclass correlation coefficients (ICC) and Bland-Altman plots. RESULTS: Mean MIP values were 58.2 and 94.0 cmH2O in NMD and control subjects, respectively (p<0.001). SNIPCL was greater than SNIPOP in NMD (51.9 ±31.0 vs. 36.9 ±25.4 cmH2O; p<0.001) as well as in controls (89.2 ±28.1 vs. 69.2 ±29.2 cmH2O; p<0.001). In both populations, the ICC between MIP and SNIPCL (NMD = 0.78, controls = 0.35) was higher than for MIP and SNIPOP (NMD = 0.53, controls = 0.06). In addition, SNIPCL was more often able to exclude inspiratory muscle weakness than SNIPOP. CONCLUSIONS: SNIPCL values are systematically higher than SNIPOP in both normal subjects and NMD patients. Therefore, SNIPCL is a useful complementary test for ruling out inspiratory muscle weakness in individuals with low MIP values.
Assuntos
Pressões Respiratórias Máximas/métodos , Doenças Neuromusculares/diagnóstico , Músculos Respiratórios/fisiologia , Olfato , Adulto , Idoso , Feminino , Humanos , Masculino , Pressões Respiratórias Máximas/instrumentação , Pessoa de Meia-Idade , Doenças Neuromusculares/fisiopatologia , Nariz/fisiologia , Músculos Respiratórios/fisiopatologiaRESUMO
Cryptosporidiosis in young children prompts local inflammation in the intestinal tract. We studied a cohort of young children with cryptosporidiosis to determine whether systemic inflammatory responses occur and, if so, to evaluate whether inflammation persists after infection. Cryptosporidiosis was associated with increased levels of interleukin-8 and tumor necrosis factor- alpha systemically, which persisted at 6 months after enrollment. The level of intestinal tumor necrosis factor- alpha was elevated at enrollment, but elevated levels did not persist. Worsening of malnutrition, particularly stunting, was observed after infection. The association of cryptosporidiosis, inflammation, and stunting in children with cryptosporidiosis warrants further evaluation.
Assuntos
Criptosporidiose/metabolismo , Interferon gama/metabolismo , Interleucinas/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Antígenos de Protozoários/sangue , Estudos de Coortes , Feminino , Humanos , Lactente , Interferon gama/sangue , Masculino , Receptores do Fator de Necrose Tumoral/sangueRESUMO
AIM: p53 is the most frequently altered gene in human cancer. It was expected to be the principle marker for chemo/radiosensitivity, resistance, tumor recurrence and ultimate survival, but is no longer considered a universal prognostic factor. Different alterations in the p53 gene have led to conflicting results depending on cell/tissue specificities and on radiation and drug specificities. METHODS: We evaluated the properties of isogenic and isophenotypic cell lines from the K1 papillary thyroid carcinoma in which p53 function was disrupted either by mutation (expression of dominant-negative p53, 143(ala)) or by inactivation (expression of human papilloma virus protein HPV16 E6). Their proliferation, their propensity to trigger apoptosis and their survival were analyzed after treatment with cisplatin (CDDP). RESULTS: Only K1 lines with wild-type p53 had significantly accumulated apoptotic bodies 72 h after treatment. Despite their incapacity to trigger apoptosis in response to CDDP treatment, the survival of K1 cell lines in which p53 expression was altered was not significantly different from the survival of K1 cell lines expressing wild-type p53. In addition, the order of magnitude of resistance of K1 cells in which p53 was mutated was similar to that in which p53 was totally inactivated, although the pathways involved may be different. CONCLUSIONS: These results show that the means by which p53 expression is disrupted and the consequence on downstream pathways regulated by p53 deserve to be considered in order to elucidate some apparently conflicting responses of this gene.
Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Proteína Supressora de Tumor p53/fisiologia , Dano ao DNA , Humanos , Neoplasias da Glândula Tireoide/patologia , Células Tumorais CultivadasRESUMO
BACKGROUND: A previous study at the GHESKIO HIV clinic confirmed that highly active antiretroviral therapy (HAART) prophylaxis reduced mother-to-child transmission (MTCT) and infant mortality in Haiti. This analysis looks at maternal outcomes in this cohort after delivery. METHODS: Records of 508 HIV-positive Haitian women who delivered between 1999 and 2005 were analyzed. We examined mortality, loss to follow-up, time to death or HAART initiation, and time of decline of CD4 count to 350 cells/µL. RESULTS: One hundred seventy women reached a CD4 ≤200 or developed clinical AIDS and were started on long-term HAART. The median CD4 count at HAART initiation was 178 (interquartile range, 106-227). CD4 decline was stratified by CD4 at delivery to project the mean months to a CD4 of 350. With an initial CD4 of 350-499 cells/µL, it was 19 months (95% confidence interval: 14 to 28) while with a CD4 >500 cells/µL, it was 71 months (95% confidence interval: 59 to 88). At study close, 257 women remained in follow-up, with loss to follow-up 3 times less in those on HAART (3.2/100 person-years) than those not on HAART (9.8/100 person-years). CONCLUSIONS: The threshold for starting treatment was often missed in HIV-infected women after delivery. Success of follow-up of women after delivery was favorably influenced by being on HAART. Women with high (>500) initial CD4 counts had a protracted time (5-7 years) before they reach a threshold CD4 count, in contrast to those with CD4 <500 cells/µL. Strategies for postpartum treatment of women should be informed by the speed with which they are likely to progress.
Assuntos
Infecções por HIV/complicações , Infecções por HIV/terapia , Complicações Infecciosas na Gravidez/terapia , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Infecções por HIV/imunologia , Infecções por HIV/mortalidade , Haiti/epidemiologia , Humanos , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Cuidado Pós-Natal , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/mortalidade , Estudos Retrospectivos , Fatores de TempoRESUMO
Dengue is endemic to Haiti but not recognized as an important illness in the autochthonous population. To evaluate the prevalence of antibodies to dengue virus (DENV), serum samples from infants and young children 7-36 months of age (n = 166) were assayed by plaque reduction neutralization assays to each DENV serotype. Dengue virus serotype 1 had infected 40% of this study population, followed by serotype 2 (12%), serotype 3 (11%), and serotype 4 (2%). Fifty-three percent of infants and young children less than 12 months of age had already experienced DENV infection, and the seroprevalence of antibody to DENV increased to 65% by 36 months. Heterotypic antibody responses were an important component of the total dengue immunity profile.
Assuntos
Vírus da Dengue/imunologia , Dengue/epidemiologia , Dengue/imunologia , Anticorpos Antivirais/sangue , Pré-Escolar , Vírus da Dengue/classificação , Feminino , Humanos , Imunidade Humoral , Lactente , Masculino , Sorotipagem , População UrbanaRESUMO
OBJECTIVES: To describe the effectiveness of a program designed to reduce the rate of mother-to-child transmission (MTCT) of HIV at the primary HIV testing and treatment center in Haiti between 1999 and 2004. METHODS: All pregnant, HIV-positive women who attended the major HIV testing and treatment clinic in Port-au-Prince, Haiti, between March 1999 and December 2004 were asked to participate in an MTCT prevention program. Of the 650 women who participated, 73.3% received zidovudine (AZT), 2.9% received nevirapine (NVP), and 10.1% received triple-drug therapy when it became available in 2003 and if clinical/laboratory indications were met. Approximately 13.8% received no antiretroviral medication. All participants received cotrimoxazole prophylaxis and infant formula for their children. Kaplan-Meier survival analysis and the log rank test were used to evaluate program impact on child survival. RESULTS: Complete data were available for 348 mother-infant pairs who completed the program to prevent MTCT of HIV. The rate of MTCT in the study was 9.2% (95% CI: 6.14-12.24), in contrast to the historical mother-to-child transmission rate of 27% in Haiti. HIV-positive infants were less likely to survive than HIV-negative infants at 18 months of follow-up (chi(2) = 19.06, P < .001, log rank test). Infant survival improved with early pediatric diagnosis and antiretroviral treatment. CONCLUSIONS: The MTCT prevention program described proved to be feasible and effective in reducing vertical HIV transmission in Haiti. The authors emphasize the need to expand testing, extend services to rural areas, and implement early HIV diagnosis to reduce infant mortality.
Assuntos
Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Adolescente , Adulto , Criança , Feminino , Haiti , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Adulto JovemRESUMO
OBJECTIVES: Many Haitian adolescents and youth are highly vulnerable to HIV infection. It was important to define the risk factors of the young people who are already seeking care. METHODS: Among 3391 sexually active 13- to 25-year-olds in our Voluntary Counseling and Testing (VCT) Center in Port-au-Prince from October 2005 to September 2006, we assessed associations between demographic and behavioral factors and HIV status using multivariable logistic regression analyses. RESULTS: We diagnosed HIV infection in 6.3% of 2533 females and 5.5% of 858 males. Age-specific prevalence was 3.4% for 13- to 15-year-olds, 4.7% for 16-19, and 6.8% for 20-25 (P = 0.02). Poor education, not residing with parents, currently or formerly married, having a child, and being self-referred or referred by others VCT services were significant predictors of HIV in females. HIV infection was associated with considering oneself at higher risk, although most youth did not recognize this risk. HIV in females was also associated with suspected/confirmed sexually transmitted infection, especially genital ulcers (ORadj = 2.28, 95% confidence interval: 1.26 to 4.13), years of sexual activity (Ptrend = 0.07), and suspicion that partners had other partners or an sexually transmitted infection. Among males, HIV was associated with drug use (though uncommon) and sexual debut with a casual/unknown person (ORadj = 3.18, 95% confidence interval: 1.58 to 6.42). HIV-infected young people were more likely to be rapid plasma reagin positive and less likely to use condoms. CONCLUSION: Young Haitians are a key target for HIV prevention and care and avail themselves readily of youth-focused VCT services.
Assuntos
Infecções por HIV/epidemiologia , Adolescente , Adulto , Aconselhamento , Cultura , Educação , Feminino , Infecções por HIV/psicologia , Haiti/epidemiologia , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Fatores de Risco , Comportamento Sexual , Adulto JovemRESUMO
BACKGROUND: Since 1999 GHESKIO, a large voluntary counseling and HIV testing center in Port-au-Prince, Haiti, has had an ongoing collaboration with the Haitian Ministry of Health to reduce the rate of mother to child HIV transmission. There are limited data on the ability to administer complex regimens for reducing mother to child transmission and on risk factors for continued transmission and infant mortality within programmatic settings in developing countries. METHODS AND FINDINGS: We analyzed data from 551 infants born to HIV-infected mothers seen at GHESKIO, between 1999 and 2005. HIV-infected mothers and their infants were given "short-course" monotherapy with antiretrovirals for prophylaxis; and, since 2003, highly active antiretroviral therapy (HAART) when clinical or laboratory indications were met. Infected women seen in the pre-treatment era had 27% transmission rates, falling to 10% in this cohort of 551 infants, and to only 1.9% in infants of women on HAART. Mortality rate after HAART introduction (0.12 per year of follow-up [0.08-0.16]) was significantly lower than the period before the availability of such therapy (0.23 [0.16-0.30], P<0.0001). The effects of maternal health, infant feeding, completeness of prophylaxis, and birth weight on mortality and transmission were determined using univariate and multivariate analysis. Infant HIV-1 infection and low birth weight were associated with infant mortality in less than 15 month olds in multivariate analysis. CONCLUSIONS: Our findings demonstrate success in prevention of mother-to-child HIV transmission and mortality in a highly resource constrained setting. Elements contributing to programmatic success include provision of HAART in the context of a comprehensive program with pre and postnatal care for both mother and infant.
Assuntos
Países em Desenvolvimento , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Adulto , Terapia Antirretroviral de Alta Atividade , Estudos de Coortes , Feminino , Infecções por HIV/mortalidade , Infecções por HIV/prevenção & controle , HIV-1/fisiologia , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Doenças do Recém-Nascido/mortalidade , Doenças do Recém-Nascido/prevenção & controle , Fatores de Risco , Resultado do TratamentoRESUMO
With global efforts to scale up the prevention of mother-to-child transmission services and pediatric antiretroviral therapy, there is an urgent need to introduce a simple, low-cost infant human immunodeficiency virus test in the field. We postulated that the p24 antigen capture enzyme-linked immunosorbent assay could be simplified by eliminating signal amplification without compromising diagnostic accuracy.
Assuntos
Síndrome da Imunodeficiência Adquirida/diagnóstico , Proteína do Núcleo p24 do HIV/análise , HIV-1 , Diagnóstico Precoce , Ensaio de Imunoadsorção Enzimática , Humanos , Recém-Nascido , RNA Viral/sangue , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Data are limited about the effectiveness of pediatric antiretroviral therapy (ART) in low-income countries. METHODS: We report the outcomes of consecutively treating 236 human immunodeficiency virus type 1 (HIV-1)-infected treatment-naive children with triple ART in Port-au-Prince, Haiti, between 1 May 2003 and 30 April 2006. RESULTS: Kaplan-Meier survival analysis at follow-up demonstrated that 191 children (81%) remained in care, 21 (9%) were dead, and 24 (10%) were lost to follow-up. Independent baseline predictors of mortality were age <18 months, CD4(+) T cell percentage < or =5%, and weight-for-age Z score (WAZ) less than -3. Twelve months into ART, 56% of tested subjects had undetectable HIV-1 RNA loads. Median CD4(+) T cell percentages at 12 months increased by 15%, 11%, and 5% in children with baseline percentages of < or =5%, 6%-24%, and > or =25%, respectively (P<.01). The median WAZ at 12 months increased by 1.0, 0.6, and 0.2 in children with baseline WAZ less than -2, -2 to -1.1, and -1 or more, respectively (P<.01). CONCLUSION: With continuous donor support, trained providers, and the availability of pediatric antiretroviral drug formulations, it proved feasible to deliver pediatric ART in Haiti. The effectiveness of this program should encourage efforts to make ART available for HIV-infected children in poor countries.
Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/mortalidade , Criança , Seguimentos , HIV-1 , Haiti/epidemiologia , Humanos , Pobreza , Análise de Sobrevida , Resultado do Tratamento , Carga ViralRESUMO
BACKGROUND: Haiti is a country with a heavy burden of HIV infection in childbearing women. Previous studies have shown that early infant deaths are common in children of HIV-infected women. This study was designed to define the rates of and risk factors for systemic bacterial and mycobacterial infection in such children and to identify the causative agents. METHODS: A cohort of 120 children born to HIV-infected mothers between May 2001 and December 2003 were prospectively observed to 15 months of age. They received comprehensive pediatric care at the GHESKIO Centers. Children were assigned to being HIV-infected by serology, RNA detection, and/or defining clinical illnesses. Blood cultures were obtained before giving antibiotics in children who were febrile or chronically ill. Blood cultures also were obtained at selected visits on well children. RESULTS: The mortality rate in the first 15 months was high, 22 of 106 (207/1,000 live births) in these children. Sixteen (70%) deaths were within 6 months of birth. Fourty-eight blood cultures had clinically significant organisms of which 38 were Staphylococcus aureus. Blood cultures were more likely to be positive in symptomatic and in HIV-infected children. CONCLUSIONS: Despite perinatal HIV treatment, mortality in children born to HIV-infected mothers remained high. Bacteremia, particularly with Staphylococcus aureus, is a partial explanation for excess illness.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Bacteriemia/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/transmissão , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Estudos de Coortes , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Haiti/epidemiologia , Humanos , Transmissão Vertical de Doenças Infecciosas , Estudos Prospectivos , Taxa de SobrevidaRESUMO
OBJECTIVES: To describe the effectiveness of a program designed to reduce the rate of mother-to-child transmission (MTCT) of HIV at the primary HIV testing and treatment center in Haiti between 1999 and 2004. METHODS: All pregnant, HIV-positive women who attended the major HIV testing and treatment clinic in Port-au-Prince, Haiti, between March 1999 and December 2004 were asked to participate in an MTCT prevention program. Of the 650 women who participated, 73.3 percent received zidovudine (AZT), 2.9 percent received nevirapine (NVP), and 10.1 percent received triple-drug therapy when it became available in 2003 and if clinical/laboratory indications were met. Approximately 13.8 percent received no antiretroviral medication. All participants received cotrimoxazole prophylaxis and infant formula for their children. Kaplan-Meier survival analysis and the log rank test were used to evaluate program impact on child survival. RESULTS: Complete data were available for 348 mother-infant pairs who completed the program to prevent MTCT of HIV. The rate of MTCT in the study was 9.2 percent (95 percent CI: 6.14-12.24), in contrast to the historical mother-to-child transmission rate of 27 percent in Haiti. HIV-positive infants were less likely to survive than HIV-negative infants at 18 months of follow-up (χ2 = 19.06, P < .001, log rank test). Infant survival improved with early pediatric diagnosis and antiretroviral treatment. CONCLUSIONS: The MTCT prevention program described proved to be feasible and effective in reducing vertical HIV transmission in Haiti. The authors emphasize the need to expand testing, extend services to rural areas, and implement early HIV diagnosis to reduce infant mortality.
OBJETIVOS: Describir la eficacia de un programa diseñado para reducir la tasa de transmisión del VIH de madre a hijo (TMH) en el principal centro de diagnóstico y tratamiento de esa infección en Haití entre 1999 y 2004. MÉTODOS: Se invitó a participar en un programa para la prevención de la TMH a todas las embarazadas positivas al VIH que asistían a la clínica principal de diagnóstico y tratamiento de la infección por el VIH en Puerto Príncipe, Haití, entre marzo de 1999 y diciembre de 2004. De las 650 mujeres que participaron, 73,3 por ciento recibieron zidovudina (AZT), 2,9 por ciento nervirapine (NVP) y 10,1 por ciento tripleterapia cuando esta se hizo disponible en 2003 y cumplían los indicadores clínicos y de laboratorio requeridos. Aproximadamente 13,8 por ciento no recibió medicamentos antirretrovirales. Todas las participantes recibieron el tratamiento profiláctico con cotrimoxazole y fórmula infantil para sus hijos. Para evaluar el impacto del programa sobre la supervivencia infantil se aplicó el análisis de supervivencia de Kaplan-Meier y la prueba de rangos logarítmicos. RESULTADOS: Se obtuvieron los datos completos de 348 parejas madre-hijo que terminaron el programa de prevención de la TMH del VIH. La tasa de TMH en el estudio fue de 9,2 por ciento (intervalo de confianza de 95 por ciento: 6,14 a 12,24), frente a una tasa de TMH histórica en Haití de 27 por ciento. A los 18 meses de seguimiento, los niños positivos al VIH presentaron una menor probabilidad de supervivencia que los negativos (χ2 = 19,06; P < 0,001; prueba de rangos logarítmicos). La supervivencia de los niños aumentó con el diagnóstico y el tratamiento antirretroviral pediátricos tempranos. CONCLUSIONES: El programa de prevención de la TMH descrito demostró su factibilidad y eficacia para reducir la transmisión vertical del VIH en Haití. Los autores sub rayan la necesidad de extender el tamizaje y los servicios a áreas rurales, así como de implementar el diagnóstico temprano del VIH para reducir la mortalidad infantil
Assuntos
Humanos , Feminino , Recém-Nascido , Lactente , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Haiti , Avaliação de Programas e Projetos de Saúde , Adulto JovemRESUMO
BACKGROUND: HIV voluntary counseling and testing (VCT) may be an effective strategy to prevent transmission of HIV in developing countries. Hypothesizing that primary care services and HIV VCT have synergistic benefits, we examine the feasibility, the demand, and the effect of integrating on-site primary care services into VCT at a stand-alone VCT center in Port au Prince, Haiti. METHODS: Through a retrospective review of patient records, we describe the integration of primary care services at the Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) VCT center between1985 and 2000. RESULTS: Between 1985 and 1999, services for HIV care, tuberculosis care, treatment of sexually transmitted diseases, and reproductive health were sequentially integrated into HIV VCT at GHESKIO. The number of new people seeking voluntary counseling and testing at GHESKIO increased from 142 in 1985 to 8175 in 1999, with an increasing percentage of women, adolescents, symptom-free clients, and self-referred clients. Of new adults seeking VCT in 1999, the center was able to provide AIDS care to 17%, tuberculosis treatment to 6%, sexually transmitted infection management to 18%, and family planning to 19%. HIV transmission between discordant couples was 0 infections/100 follow-up years (95% CI, 0-3.2); vertical transmission from mother to child was 11 infections/100 live births (95% CI, 4.6-21.9); These rates are significantly lower than expected rates of transmission in Haiti. CONCLUSIONS: This report demonstrates the feasibility, demand, and effective synergy of integrating on-site primary care services into HIV VCT in Haiti. VCT is a good entry point for people in need of services for communicable diseases and reproductive health, and, reciprocally, services attract more people to VCT, including populations that are at high risk for HIV infection. This program is being duplicated elsewhere in Haiti and can serve as a model for other countries.