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Background: Daily oral pre-exposure prophylaxis (PrEP) is effective in preventing HIV infection, but no study has evaluated combination prevention interventions with PrEP for transgender women (TGW) and men who have sex with men (MSM) who sell sex. Methods: The Combination Prevention Effectiveness (COPE) study was a community-based, non-randomized implementation study in Bangkok and Pattaya, Thailand. Participants were HIV-negative MSM and TGW aged 18-26 years who reported exchanging sex with men in the prior 12 months and who met 2014 U.S. Public Health Service PrEP eligibility criteria. The intervention included quarterly HIV testing, semiannual testing for sexually transmitted infections, provision of condoms with lubricant, and the opportunity to initiate or end daily oral PrEP use at any time during study participation. Participants taking PrEP received monthly adherence counseling and short message service reminders. The primary outcome was HIV incidence rate ratio (IRR) on PrEP vs. not on PrEP. Secondary outcomes were PrEP initiation, PrEP use at 12 months, and PrEP adherence. Findings: From October 2017 to August 2019, 846 participants were enrolled: 531 (62.8%) immediately initiated PrEP; 104 (12.3%) subsequently initiated PrEP, and 211 (24.9%) never initiated PrEP. Among those initiating PrEP within 30 days of enrollment; 85.9% were on PrEP at the 12-months. When taking PrEP, participants reported adherent PrEP use at 94.2% of quarterly assessments. Ten HIV seroconversions occurred without PrEP use (incidence rate [IR] = 3.42 per 100 person-years [PY]; 95% CI = 1.64-6.30), while zero cases occurred with PrEP use (IR = 0.0 per 100PY; 95% CI = 0.0-0.62), with IRR = 0.0 (95% CI = 0.0-0.22; p < 0.001). Interpretation: Young Thai MSM and TGW who exchange sex can have high PrEP uptake, persistence and adherence, and low HIV incidence when offered in supportive community-based settings. Funding: U.S. National Institute of Allergy and Infectious Diseases; Centers for Disease Control and Prevention.
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A mass Japanese encephalitis (JE) immunization campaign for children aged 9 months through 12 years was conducted in 2013 in Battambang province, western Cambodia. Vaccinators working at almost 2,000 immunization posts in approximately 800 villages provided vaccinations to almost 310,000 children using one dose of Chengdu Institute of Biological Products' live, attenuated SA14-14-2 JE vaccine (CD-JEV), achieving a coverage rate of greater than 90%. Lessons learned, in general for mass vaccination campaigns and specifically for vaccination with CD-JEV, are described. These observations will be of benefit for public health officials and to help inform planning for future campaigns for JE or other vaccine-preventable diseases in Cambodia and elsewhere.
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Encefalite Japonesa , Criança , Humanos , Camboja , Encefalite Japonesa/epidemiologia , Encefalite Japonesa/prevenção & controle , Vacinação , Programas de Imunização , ImunizaçãoRESUMO
INTRODUCTION: Japanese encephalitis (JE) virus is the most common cause of vaccine-preventable encephalitis in Asia. The SA14-14-2 JE vaccine manufactured by Chengdu Institute of Biological Products has been shown to be safe and effective in clinical trials and childhood routine immunization programs. However, there are few published reports describing results of surveillance for adverse events following immunization (AEFI) when the vaccine is used in mass campaigns. We describe the results of AEFI surveillance following a 2013 vaccination campaign among almost 310,000 children aged 9 months-12 years in Battambang Province, Cambodia. METHODS: Routine AEFI surveillance was strengthened by staff training and supplemented by active hospital surveillance. An AEFI was defined as any sign, symptom, or disease temporally associated (i.e., within 4 weeks) with receipt of the vaccine, irrespective of whether it was considered related to immunization. Data were collected on standardized forms and causality assessments were conducted for serious AEFI. RESULTS: Passive and active surveillance detected 28 AEFI for an overall incidence of 9.0 AEFI per 100,000 doses administered. The most frequent events were vasovagal episodes (n = 7, 25%) and rash (n = 6, 21%), and most other events were common childhood conditions such as fever and vomiting. Three AEFI were classified as serious, including one hypersensitivity reaction and two meningoencephalitis cases. Of these, the hypersensitivity event was the only serious AEFI classified as being consistent with a causal association to immunization. CONCLUSIONS: Most reported adverse events were conditions that commonly occur after other childhood vaccinations or independently of vaccination, and in the context of careful monitoring for serious AEFI only one serious event consistent with a causal association with immunization was identified. These results support the good safety profile of the SA14-14-2 JE vaccine, and provide reassuring data as the vaccine's use expands.
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Encefalomielite Aguda Disseminada , Hipersensibilidade , Vacinas contra Encefalite Japonesa , Sistemas de Notificação de Reações Adversas a Medicamentos , Camboja/epidemiologia , Criança , Pré-Escolar , Encefalomielite Aguda Disseminada/prevenção & controle , Humanos , Hipersensibilidade/etiologia , Programas de Imunização , Lactente , Vacinas contra Encefalite Japonesa/efeitos adversos , Vacinação/efeitos adversosRESUMO
PURPOSE: To examine how recent sex work is identified and the HIV risk factors and service needs among Thai cisgender men who have sex with men (MSM) and transgender women (TGW) who exchange sex. METHODS: MSM and TGW in Bangkok and Pattaya who exchanged sex in the last year (n = 890) were recruited through social media, outreach, and word-of-mouth. Recent sex exchange was based on the primary question, "In the last 30 days, have you sold or traded sex"; secondary questions (regarding income source and client encounters) were also investigated. RESULTS: Overall, 436 (48%) participants engaged in sex work in the last 30 days; among those, 270 (62%) reported exchanging sex by the primary question, and 160 (37%) based on secondary questions only. Recent sex exchange was associated with gonorrhea, syphilis, discussing PrEP with others, and using condoms, alcohol, methamphetamine, amyl nitrate, and Viagra. Exchanging sex based on secondary questions only was associated with being in a relationship, social media recruitment, less recent anal intercourse, and not discussing PrEP. CONCLUSIONS: Thai MSM and TGW who exchange sex need regular access to HIV/STI prevention, testing, and treatment services, and multiple approaches to assessing sex work will help identify and serve this diverse and dynamic population.
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Infecções por HIV , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Pessoas Transgênero , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Infecções Sexualmente Transmissíveis/epidemiologia , Tailândia/epidemiologiaRESUMO
In Thailand, pre-exposure prophylaxis (PrEP) is recommended for human immunodeficiency virus (HIV) prevention among at-risk men who have sex with men (MSM). We modeled the impact of PrEP and condom use as independent and combined interventions on the estimated number of HIV infections among a hypothetical population of 10,000 MSM in Bangkok, Thailand. Our model demonstrated a 92% (95% confidence interval 89.7, 94.2) reduction in HIV infections among Thai MSM who took daily PrEP and self-reported using condoms correctly and consistently (100% condom use). Increased use of PrEP and condoms likely would have a substantial impact on the HIV epidemic in Thailand.
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Preservativos/estatística & dados numéricos , Infecções por HIV/prevenção & controle , Homossexualidade Masculina/estatística & dados numéricos , Profilaxia Pré-Exposição , Adulto , Fármacos Anti-HIV/administração & dosagem , Estudos de Coortes , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Homossexualidade Masculina/psicologia , Humanos , Masculino , Adesão à Medicação , Sexo Seguro , Comportamento Sexual , Tailândia/epidemiologiaRESUMO
BACKGROUND: Pre-exposure prophylaxis (PrEP) is highly effective in the prevention of HIV acquisition, particularly for men who have sex with men (MSM). Questions remain on the benefits of PrEP and implementation strategies for those at occupational risk of HIV acquisition in sex work, as well as on methods to support adherence among young people who initiate PrEP. OBJECTIVE: The Combination Prevention Effectiveness study for young cisgender MSM and transgender women (TGW) aims to assess the effectiveness and cost-effectiveness of a combination intervention among HIV-uninfected young MSM and TGW engaged in sex work in Thailand. METHODS: This open-label, nonrandomized assessment compares the relative effectiveness of a combination prevention intervention with and without daily oral emtricitabine and tenofovir disoproxil fumarate (Truvada) PrEP with SMS-based adherence support. HIV-uninfected young MSM and TGW aged 18 to 26 years in Bangkok and Pattaya who self-report selling/exchanging sex at least once in the previous 12 months are recruited by convenience sampling and peer referral and are eligible regardless of their intent to initiate PrEP. At baseline, participants complete a standard assessment for PrEP eligibility and may initiate PrEP then or at any time during study participation. All participants complete a survey and HIV testing at baseline and every 3 months. Participants who initiate PrEP complete monthly pill pickups and may opt-in to SMS reminders. All participants are sent brief weekly SMS surveys to assess behavior with additional adherence questions for those who initiated PrEP. Adherence is defined as use of 4 or more pills within the last 7 days. The analytic plan uses a person-time approach to assess HIV incidence, comparing participant time on oral PrEP to participant time off oral PrEP for 12 to 24 months of follow-up, using a propensity score to control for confounders. Enrollment is based on the goal of observing 620 person-years (PY) on PrEP and 620 PY off PrEP. RESULTS: As of February 2019, 445 participants (417 MSM and 28 TGW) have contributed approximately 168 PY with 95% (73/77) retention at 12 months. 74.2% (330/445) of enrolled participants initiated PrEP at baseline, contributing to 134 PY of PrEP adherence, 1 PY nonadherence, and 33 PY PrEP nonuse/noninitiation. Some social harms, predominantly related to unintentional participant disclosure of PrEP use and peer stigmatization of PrEP and HIV, have been identified. CONCLUSIONS: The majority of cisgender MSM and TGW who exchange sex and participate in this study are interested in PrEP, report taking sufficient PrEP, and stay on PrEP, though additional efforts are needed to address community misinformation and stigma. This novel multilevel, open-label study design and person-time approach will allow evaluation of the effectiveness and cost-effectiveness of combination prevention intervention in the contexts of both organized sex work and exchanged sex. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/15354.
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Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV/efeitos dos fármacos , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Saúde Global , Infecções por HIV/tratamento farmacológico , Humanos , National Institute of Allergy and Infectious Diseases (U.S.) , Vigilância em Saúde Pública , Encaminhamento e Consulta , Pesquisa , Estados UnidosAssuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/farmacocinética , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição , Inibidores da Transcriptase Reversa/farmacocinética , Adulto , Feminino , Transcriptase Reversa do HIV/antagonistas & inibidores , Humanos , Ativação Linfocitária/efeitos dos fármacos , Masculino , Fosforilação , Especificidade por Substrato , Carga ViralRESUMO
Although group B Streptococcus (GBS) is a leading cause of severe invasive disease in young infants worldwide, epidemiologic data and knowledge about risk factors for the disease are lacking from low- to middle-income countries. To determine the epidemiology of invasive GBS disease among young infants in a setting with high maternal HIV infection, we conducted hospital-based surveillance during 2004-2008 in Soweto, South Africa. Overall GBS incidence was 2.72 cases/1,000 live births (1.50 and 1.22, respectively, among infants with early-onset disease [EOD] and late-onset [LOD] disease). Risk for EOD and LOD was higher for HIV-exposed than HIV-unexposed infants. GBS serotypes Ia and III accounted for 84.0% of cases, and 16.9% of infected infants died. We estimate that use of trivalent GBS vaccine (serotypes Ia, Ib, and III) could prevent 2,105 invasive GBS cases and 278 deaths annually among infants in South Africa; therefore, vaccination of all pregnant women in this country should be explored.
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Coinfecção , Infecções por HIV/epidemiologia , Sepse/epidemiologia , Sepse/etiologia , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/etiologia , Streptococcus agalactiae , Fatores Etários , Criança , Pré-Escolar , Infecções por HIV/história , História do Século XXI , Humanos , Incidência , Lactente , Recém-Nascido , Testes de Sensibilidade Microbiana , Mortalidade , Vigilância da População , Prevalência , Risco , Sepse/história , Sorotipagem , África do Sul/epidemiologia , Infecções Estreptocócicas/história , Infecções Estreptocócicas/mortalidade , Vacinas Estreptocócicas/imunologia , Streptococcus agalactiae/classificação , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/imunologiaRESUMO
BACKGROUND: Tenofovir-emtricitabine (TDF-FTC) pre-exposure prophylaxis (PrEP) has been found to be effective for prevention of HIV infection in several clinical trials. Two studies of TDF PrEP among men who have sex with men showed slight bone mineral density (BMD) loss. We investigated the effect of TDF and the interaction of TDF and hormonal contraception on BMD among HIV-uninfected African men and women. METHOD: We evaluated the effects on BMD of using daily oral TDF-FTC compared to placebo among heterosexual men and women aged 18-29 years enrolled in the Botswana TDF2 PrEP study. Participants had BMD measurements at baseline and thereafter at 6-month intervals with dual-energy X-ray absorptiometry (DXA) scans at the hip, spine, and forearm. RESULTS: A total of 220 participants (108 TDF-FTC, 112 placebo) had baseline DXA BMD measurements at three anatomic sites. Fifteen (6.8%) participants had low baseline BMD (z-score of <-2.0 at any anatomic site), including 3/114 women (2.6%) and 12/106 men (11.3%) (pâ=â0.02). Low baseline BMD was associated with being underweight (pâ=â0.02), having high blood urea nitrogen (pâ=â0.02) or high alkaline phosphatase (pâ=â0.03), and low creatinine clearance (pâ=â0.04). BMD losses of >3.0% at any anatomic site at any time after baseline were significantly greater for the TDF-FTC treatment group [34/68 (50.0%) TDF-FTC vs. 26/79 (32.9%) placebo; pâ=â0.04]. There was a small but significant difference in the mean percent change in BMD from baseline for TDF-FTC versus placebo at all three sites at month 30 [forearm -0.84% (pâ=â0.01), spine -1.62% (pâ=â0.0002), hip -1.51% (pâ=â0.003)]. CONCLUSION: Use of TDF-FTC was associated with a small but statistically significant decrease in BMD at the forearm, hip and lumbar spine. A high percentage (6.8%) of healthy Batswana young adults had abnormal baseline BMD Further evaluation is needed of the longer-term use of TDF in HIV-uninfected persons. TRIAL REGISTRATION: ClinicalTrials.gov NCT00448669.
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Fármacos Anti-HIV/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Emtricitabina/administração & dosagem , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição/métodos , Tenofovir/administração & dosagem , Absorciometria de Fóton , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Botsuana , Controle de Doenças Transmissíveis , Emtricitabina/efeitos adversos , Feminino , Antebraço/diagnóstico por imagem , Quadril/diagnóstico por imagem , Humanos , Estudos Longitudinais , Masculino , Coluna Vertebral/diagnóstico por imagem , Tenofovir/efeitos adversos , Adulto JovemRESUMO
We examined CD4 cell count and plasma viral load patterns among Botswana TDF/FTC Oral HIV Prophylaxis Trial (TDF2 study) participants who seroconverted, comparing participants assigned to receive tenofovir/emtricitabine with participants assigned to receive placebo. We also evaluated for antiretroviral drug resistance among the breakthrough HIV infections. Among nine seroconverters assigned to tenofovir/emtricitabine and 24 to placebo, there were no significant differences in their CD4 cell count or viral load profiles over time. Of the four participants who seroconverted on-study while receiving tenofovir/emtricitabine, none became infected as a result of drug-resistant HIV; moreover, no resistance mutations emerged following seroconversion.
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Fármacos Anti-HIV/uso terapêutico , Quimioprevenção/métodos , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Profilaxia Pós-Exposição/métodos , Carga Viral , Adenina/análogos & derivados , Adenina/uso terapêutico , Botsuana/epidemiologia , Contagem de Linfócito CD4 , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Emtricitabina , HIV/isolamento & purificação , Infecções por HIV/imunologia , Heterossexualidade , Humanos , Organofosfonatos/uso terapêutico , Plasma/virologia , TenofovirRESUMO
BACKGROUND: In resource-limited settings, mothers infected with human immunodeficiency virus type 1 (HIV-1) face a difficult choice: breastfeed their infants but risk transmitting HIV-1 or not breastfeed their infants and risk the infants dying of other infectious diseases or malnutrition. Recent results from observational studies and randomized clinical trials indicate daily administration of nevirapine to the infant can prevent breast-milk HIV-1 transmission. METHODS: Data from 5396 mother-infant pairs who participated in 5 randomized trials where the infant was HIV-1 negative at birth were pooled to estimate the efficacy of infant nevirapine prophylaxis to prevent breast-milk HIV-1 transmission. Four daily regimens were compared: nevirapine for 6 weeks, 14 weeks, or 28 weeks, or nevirapine plus zidovudine for 14 weeks. RESULTS: The estimated 28-week risk of HIV-1 transmission was 5.8% (95% confidence interval [CI], 4.3%-7.9%) for the 6-week nevirapine regimen, 3.7% (95% CI, 2.5%-5.4%) for the 14-week nevirapine regimen, 4.8% (95% CI, 3.5%-6.7%) for the 14-week nevirapine plus zidovudine regimen, and 1.8% (95% CI, 1.0%-3.1%) for the 28-week nevirapine regimen (log-rank test for trend, P < .001). Cox regression models with nevirapine as a time-varying covariate, stratified by trial site and adjusted for maternal CD4 cell count and infant birth weight, indicated that nevirapine reduces the rate of HIV-1 infection by 71% (95% CI, 58%-80%; P < .001) and reduces the rate of HIV infection or death by 58% (95% CI, 45%-69%; P < .001). CONCLUSIONS: Extended prophylaxis with nevirapine or with nevirapine and zidovudine significantly reduces postnatal HIV-1 infection. Longer duration of prophylaxis results in a greater reduction in the risk of infection.
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Fármacos Anti-HIV/administração & dosagem , Antibioticoprofilaxia/métodos , Infecções por HIV/prevenção & controle , HIV-1/isolamento & purificação , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Leite Humano/virologia , Nevirapina/administração & dosagem , Aleitamento Materno/estatística & dados numéricos , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Estimativa de Kaplan-Meier , Masculino , Fatores de RiscoRESUMO
BACKGROUND: Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain. METHODS: We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants. RESULTS: A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF-FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P=0.008), and dizziness (15.1% vs. 11.0%, P=0.03) than the placebo group, but the rates of serious adverse events were similar (P=0.90). Participants who received TDF-FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF-FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF-FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P=0.03). CONCLUSIONS: Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669.).
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Adenina/análogos & derivados , Antirretrovirais/uso terapêutico , Desoxicitidina/análogos & derivados , Infecções por HIV/prevenção & controle , HIV-1 , Organofosfonatos/uso terapêutico , Adenina/efeitos adversos , Adenina/uso terapêutico , Adolescente , Adulto , Antirretrovirais/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Comportamento Contraceptivo/estatística & dados numéricos , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Farmacorresistência Viral , Quimioterapia Combinada , Emtricitabina , Feminino , Soropositividade para HIV , HIV-1/genética , HIV-1/isolamento & purificação , HIV-2/genética , HIV-2/isolamento & purificação , Humanos , Estimativa de Kaplan-Meier , Masculino , Organofosfonatos/efeitos adversos , Modelos de Riscos Proporcionais , RNA Viral/sangue , Comportamento Sexual/estatística & dados numéricos , Tenofovir , Carga Viral , Adulto JovemRESUMO
BACKGROUND: We assessed morbidity rates during short intervals that accompanied weaning and cumulative mortality among HIV-exposed, uninfected infants enrolled in the postexposure prophylaxis of infants in Malawi (PEPI-Malawi) trial. METHODS: Women were counseled to stop breastfeeding (BF) by 6 months in the PEPI-Malawi trial. HIV-uninfected infants were included in this analysis starting at age 6 months. Breastfeeding and morbidity (illness and/or hospital admission and malnutrition [weight-for-age Z-score, ≤2]) were assessed during age intervals of 6-9, 9-12, and 12-15 months. BF was defined as any BF at the start and end of the interval and no breastfeeding (NBF) was defined as NBF at any time during the interval. The association of NBF with morbidity at each mutually exclusive interval was assessed using Poisson regression models controlling for other factors. Cumulative mortality among infants aged 6-15 months with BF and NBF was assessed using an extended Kaplan-Meier method. RESULTS: At age 6 months, 1761 HIV-uninfected infants were included in the study. The adjusted rate ratios for illnesses and/or hospital admission for NBF, compared with BF, was 1.7 (P < .0001) at 6-9 months, 1.66 (P = .0001) at 9-12 months, and 1.75 (P = .0008) at 12-15 months. The rates of morbidity were consistently higher among NBF infants during each age interval, compared with BF infants. The 15 months cumulative mortality among BF and NBF children was 3.5% and 6.4% (P = .03), respectively. CONCLUSIONS: Cessation of BF is associated with acute morbidity events and cumulative mortality. Prolonged BF should be encouraged, in addition to close monitoring of infant health and provision of support services.
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Aleitamento Materno/estatística & dados numéricos , Infecções por HIV/epidemiologia , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Adulto , Fármacos Anti-HIV/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Humanos , Lactente , Estimativa de Kaplan-Meier , Malaui/epidemiologia , Morbidade , Nevirapina/uso terapêutico , Distribuição de Poisson , Profilaxia Pós-Exposição , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Desmame , Zidovudina/uso terapêuticoRESUMO
BACKGROUND: The rate of bacterial meningitis declined by 55% in the United States in the early 1990s, when the Haemophilus influenzae type b (Hib) conjugate vaccine for infants was introduced. More recent prevention measures such as the pneumococcal conjugate vaccine and universal screening of pregnant women for group B streptococcus (GBS) have further changed the epidemiology of bacterial meningitis. METHODS: We analyzed data on cases of bacterial meningitis reported among residents in eight surveillance areas of the Emerging Infections Programs Network, consisting of approximately 17.4 million persons, during 1998-2007. We defined bacterial meningitis as the presence of H. influenzae, Streptococcus pneumoniae, GBS, Listeria monocytogenes, or Neisseria meningitidis in cerebrospinal fluid or other normally sterile site in association with a clinical diagnosis of meningitis. RESULTS: We identified 3188 patients with bacterial meningitis; of 3155 patients for whom outcome data were available, 466 (14.8%) died. The incidence of meningitis changed by -31% (95% confidence interval [CI], -33 to -29) during the surveillance period, from 2.00 cases per 100,000 population (95% CI, 1.85 to 2.15) in 1998-1999 to 1.38 cases per 100,000 population (95% CI 1.27 to 1.50) in 2006-2007. The median age of patients increased from 30.3 years in 1998-1999 to 41.9 years in 2006-2007 (P<0.001 by the Wilcoxon rank-sum test). The case fatality rate did not change significantly: it was 15.7% in 1998-1999 and 14.3% in 2006-2007 (P=0.50). Of the 1670 cases reported during 2003-2007, S. pneumoniae was the predominant infective species (58.0%), followed by GBS (18.1%), N. meningitidis (13.9%), H. influenzae (6.7%), and L. monocytogenes (3.4%). An estimated 4100 cases and 500 deaths from bacterial meningitis occurred annually in the United States during 2003-2007. CONCLUSIONS: The rates of bacterial meningitis have decreased since 1998, but the disease still often results in death. With the success of pneumococcal and Hib conjugate vaccines in reducing the risk of meningitis among young children, the burden of bacterial meningitis is now borne more by older adults. (Funded by the Emerging Infections Programs, Centers for Disease Control and Prevention.).
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Meningites Bacterianas/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , População Negra/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Haemophilus influenzae , Humanos , Incidência , Lactente , Recém-Nascido , Listeria monocytogenes , Masculino , Meningites Bacterianas/etnologia , Meningites Bacterianas/microbiologia , Pessoa de Meia-Idade , Neisseria meningitidis , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Streptococcus pneumoniae , Estados Unidos/epidemiologia , População Branca/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: Nevirapine and lamivudine given to mothers are transmitted to infants via breastfeeding in quantities sufficient to have biologic effects on the virus; this may lead to an increased risk of a breastfed infant's development of resistance to maternal antiretrovirals. The Kisumu Breastfeeding Study (KiBS), a single-arm open-label prevention of mother-to-child HIV transmission (PMTCT) trial, assessed the safety and efficacy of zidovudine, lamivudine, and either nevirapine or nelfinavir given to HIV-infected women from 34 wk gestation through 6 mo of breastfeeding. Here, we present findings from a KiBS trial secondary analysis that evaluated the emergence of maternal ARV-associated resistance among 32 HIV-infected breastfed infants. METHODS AND FINDINGS: All infants in the cohort were tested for HIV infection using DNA PCR at multiple study visits during the 24 mo of the study, and plasma RNA viral load for all HIV-PCR-positive infants was evaluated retrospectively. Specimens from mothers and infants with viral load >1,000 copies/ml were tested for HIV drug resistance mutations. Overall, 32 infants were HIV infected by 24 mo of age, and of this group, 24 (75%) infants were HIV infected by 6 mo of age. Of the 24 infants infected by 6 mo, nine were born to mothers on a nelfinavir-based regimen, whereas the remaining 15 were born to mothers on a nevirapine-based regimen. All infants were also given single-dose nevirapine within 48 hours of birth. We detected genotypic resistance mutations in none of eight infants who were HIV-PCR positive by 2 wk of age (specimens from six infants were not amplifiable), for 30% (6/20) at 6 wk, 63% (14/22) positive at 14 wk, and 67% (16/24) at 6 mo post partum. Among the 16 infants with resistance mutations by 6 mo post partum, the common mutations were M184V and K103N, conferring resistance to lamivudine and nevirapine, respectively. Genotypic resistance was detected among 9/9 (100%) and 7/15 (47%) infected infants whose mothers were on nelfinavir and nevirapine, respectively. No mutations were detected among the eight infants infected after the breastfeeding period (age 6 mo). CONCLUSIONS: Emergence of HIV drug resistance mutations in HIV-infected infants occurred between 2 wk and 6 mo post partum, most likely because of exposure to maternal ARV drugs through breast milk. Our findings may impact the choice of regimen for ARV treatment of HIV-infected breastfeeding mothers and their infected infants.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Aleitamento Materno , Farmacorresistência Viral/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , HIV-1/fisiologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Fármacos Anti-HIV/farmacologia , Estudos de Coortes , Farmacorresistência Viral/genética , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , Soropositividade para HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , HIV-1/imunologia , Humanos , Recém-Nascido , Quênia , Mães , Mutação/genética , Reação em Cadeia da Polimerase , Carga Viral/efeitos dos fármacosRESUMO
BACKGROUND: Effective strategies are needed for the prevention of mother-to-child HIV transmission (PMTCT) in resource-limited settings. The Kisumu Breastfeeding Study was a single-arm open label trial conducted between July 2003 and February 2009. The overall aim was to investigate whether a maternal triple-antiretroviral regimen that was designed to maximally suppress viral load in late pregnancy and the first 6 mo of lactation was a safe, well-tolerated, and effective PMTCT intervention. METHODS AND FINDINGS: HIV-infected pregnant women took zidovudine, lamivudine, and either nevirapine or nelfinavir from 34-36 weeks' gestation to 6 mo post partum. Infants received single-dose nevirapine at birth. Women were advised to breastfeed exclusively and wean rapidly just before 6 mo. Using Kaplan-Meier methods we estimated HIV-transmission and death rates from delivery to 24 mo. We compared HIV-transmission rates among subgroups defined by maternal risk factors, including baseline CD4 cell count and viral load. Among 487 live-born, singleton, or first-born infants, cumulative HIV-transmission rates at birth, 6 weeks, and 6, 12, and 24 mo were 2.5%, 4.2%, 5.0%, 5.7%, and 7.0%, respectively. The 24-mo HIV-transmission rates stratified by baseline maternal CD4 cell count <500 and ≥500 cells/mm(3) were 8.4% (95% confidence interval [CI] 5.8%-12.0%) and 4.1% (1.8%-8.8%), respectively (pâ=â0.06); the corresponding rates stratified by baseline maternal viral load <10,000 and ≥10,000 copies/ml were 3.0% (1.1%-7.8%) and 8.7% (6.1%-12.3%), respectively (pâ=â0.01). None of the 12 maternal and 51 infant deaths (including two second-born infants) were attributed to antiretrovirals. The cumulative HIV-transmission or death rate at 24 mo was 15.7% (95% CI 12.7%-19.4%). CONCLUSIONS: This trial shows that a maternal triple-antiretroviral regimen from late pregnancy through 6 months of breastfeeding for PMTCT is safe and feasible in a resource-limited setting. These findings are consistent with those from other trials using maternal triple-antiretroviral regimens during breastfeeding in comparable settings.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Aleitamento Materno , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , HIV-1/fisiologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Parto Obstétrico , Demografia , Feminino , Infecções por HIV/virologia , Humanos , Recém-Nascido , Estimativa de Kaplan-Meier , Quênia , Adesão à Medicação , Mães , Gravidez , Adulto JovemRESUMO
BACKGROUND: The World Health Organization currently recommends initiation of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-infected lactating women with CD4+ cell counts <350 cells/µL or stage 3 or 4 disease. We analyzed antiretroviral drug resistance in HIV-infected infants in the Post Exposure Prophylaxis of Infants trial whose mothers initiated HAART postpartum (with a regimen of nevirapine [NVP], stavudine, and lamivudine). Infants in the trial received single-dose NVP and a week of zidovudine (ZDV) at birth; some infants also received extended daily NVP prophylaxis, with or without extended ZDV prophylaxis. METHODS: We analyzed drug resistance in plasma samples collected from all HIV-infected infants whose mothers started HAART in the first postpartum year. Resistance testing was performed using the first plasma sample collected within 6 months after maternal HAART initiation. Categorical variables were compared by exact or trend tests; continuous variables were compared using rank-sum tests. RESULTS: Multiclass resistance (MCR) was detected in HIV from 11 (29.7%) of 37 infants. Infants were more likely to develop MCR infection if their mothers initiated HAART earlier in the postpartum period (by 14 weeks vs after 14 weeks and up to 6 months vs after 6 months, P = .0009), or if the mother was exclusively breastfeeding at the time of HAART initiation (exclusive breastfeeding vs mixed feeding vs no breastfeeding, P = .003). CONCLUSIONS: Postpartum maternal HAART initiation was associated with acquisition of MCR in HIV-infected breastfeeding infants. The risk was higher among infants whose mothers initiated HAART closer to the time of delivery or were still exclusively breastfeeding when they first reported HAART use.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Aleitamento Materno , Farmacorresistência Viral Múltipla , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Período Pós-Parto , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Plasma/virologia , RNA Viral/genética , RNA Viral/isolamento & purificaçãoRESUMO
Approximately 2 billion persons worldwide are infected with schistosomiasis and soil-transmitted helminths (STH), many in areas where endemic malaria transmission coexists. Few data exist on associations between these infections. Nested within a larger clinical trial, primigravid and secundigravid women provided blood samples for human immunodeficiency virus (HIV) testing and peripheral malaria films and stool and urine for evaluation of STH and Schistosoma spp. during their initial antenatal clinic visit. The most common parasitic infections were malaria (37.6%), S. haematobium (32.3%), and hookworm (14.4%); 14.2% of women were HIV-infected. S. haematobium infection was associated with lower malarial parasite densities (344 versus 557 parasites/µL blood; P < 0.05). In multivariate analysis, HIV and hookworm infection were independently associated with malaria infection (adjusted odds ratio = 1.9 and 95% confidence interval = 1.2-3.0 for HIV; adjusted odds ratio = 1.9 and 95% confidence interval = 1.03-3.5 for hookworm). Concurrent helminthic infection had both positive and negative effects on malaria parasitemia among pregnant women in Malawi.