RESUMO
Physiological changes during pregnancy may alter the pharmacokinetics (PK) of antituberculosis drugs. The International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1026s was a multicenter, phase IV, observational, prospective PK and safety study of antiretroviral and antituberculosis drugs administered as part of clinical care in pregnant persons living with and without HIV. We assessed the effects of pregnancy on rifampin, isoniazid, ethambutol, and pyrazinamide PK in pregnant and postpartum (PP) persons without HIV treated for drug-susceptible tuberculosis disease. Daily antituberculosis treatment was prescribed following World Health Organization-recommended weight-band dosing guidelines. Steady-state 12-hour PK profiles of rifampin, isoniazid, ethambutol, and pyrazinamide were performed during second trimester (2T), third trimester (3T), and 2-8 of weeks PP. PK parameters were characterized using noncompartmental analysis, and comparisons were made using geometric mean ratios (GMRs) with 90% confidence intervals (CI). Twenty-seven participants were included: 11 African, 9 Asian, 3 Hispanic, and 4 mixed descent. PK data were available for 17, 21, and 14 participants in 2T, 3T, and PP, respectively. Rifampin and pyrazinamide AUC0-24 and C max in pregnancy were comparable to PP with the GMR between 0.80 and 1.25. Compared to PP, isoniazid AUC0-24 was 25% lower and C max was 23% lower in 3T. Ethambutol AUC0-24 was 39% lower in 3T but limited by a low PP sample size. In summary, isoniazid and ethambutol concentrations were lower during pregnancy compared to PP concentrations, while rifampin and pyrazinamide concentrations were similar. However, the median AUC0-24 for rifampin, isoniazid, and pyrazinamide met the therapeutic targets. The clinical impact of lower isoniazid and ethambutol exposure during pregnancy needs to be determined.
Assuntos
Antituberculosos , Tuberculose , Adolescente , Feminino , Humanos , Gravidez , Antituberculosos/efeitos adversos , Antituberculosos/farmacocinética , Etambutol/efeitos adversos , Etambutol/farmacocinética , Infecções por HIV/tratamento farmacológico , Isoniazida/efeitos adversos , Isoniazida/farmacocinética , Período Pós-Parto , Estudos Prospectivos , Pirazinamida/efeitos adversos , Pirazinamida/farmacocinética , Rifampina/efeitos adversos , Rifampina/farmacocinética , Tuberculose/tratamento farmacológico , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase IV como Assunto , Estudos Observacionais como AssuntoRESUMO
The purpose of this study was to evaluate the pharmacokinetics of ritonavir-boosted fosamprenavir during pregnancy and postpartum. Amprenavir (the active moiety of fosamprenavir) and ritonavir intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy and postpartum. Plasma concentrations of amprenavir and ritonavir were measured using high-performance liquid chromatography. The target amprenavir area under the concentration-versus-time curve (AUC) was higher than the 10th percentile (27.7 µg · h/ml) of the median area under the curve for ritonavir-boosted fosamprenavir in adults receiving twice-daily fosamprenavir-ritonavir at 700 mg/100 mg. Twenty-nine women were included in the analysis. The amprenavir AUC from time zero to 12 h (AUC0-12) was lower (geometric mean ratio [GMR], 0.60 [confidence interval {CI}, 0.49 to 0.72] [P < 0.001]) while its apparent oral clearance was higher (GMR, 1.68 [CI, 1.38 to 2.03] [P < 0.001]) in the third trimester than postpartum. Similarly, the ritonavir AUC0-12 was lower in the second (GMR, 0.51 [CI, 0.28 to 0.91] [P = 0.09]) and third (GMR, 0.72 [CI, 0.55 to 0.95] [P = 0.005]) trimesters than postpartum, while its apparent oral clearance was higher in the second (GMR, 1.98 [CI, 1.10 to 3.56] [P = 0.06]) and third (GMR, 1.38 [CI, 1.05 to 1.82] [P = 0.009]) trimesters than postpartum. The amprenavir area under the curve exceeded the target for 6/8 (75%) women in the 2nd trimester, 18/28 (64%) in the 3rd trimester, and 19/22 (86.4%) postpartum, and the trough concentrations (Cmin) of amprenavir were 4- to 16-fold above the mean amprenavir-protein-adjusted 50% inhibitory concentration (IC50) of 0.146 µg/ml. Although amprenavir plasma concentrations in women receiving ritonavir-boosted fosamprenavir were lower during pregnancy than postpartum, the reduced amprenavir concentrations were still above the exposures needed for viral suppression.
Assuntos
Carbamatos/farmacocinética , Furanos/farmacocinética , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/farmacocinética , Complicações Infecciosas na Gravidez/tratamento farmacológico , Ritonavir/farmacocinética , Sulfonamidas/farmacocinética , Adulto , Área Sob a Curva , Carbamatos/efeitos adversos , Feminino , Furanos/efeitos adversos , Inibidores da Protease de HIV/efeitos adversos , Humanos , Idade Materna , Gravidez , Trimestres da Gravidez , RNA Viral/sangue , Ritonavir/efeitos adversos , Sulfonamidas/efeitos adversos , Carga ViralRESUMO
BACKGROUND: This study evaluated atazanavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples. SETTING: A nonrandomized, open-label, parallel-group, multicenter prospective study of atazanavir and cobicistat pharmacokinetics in pregnant women with HIV and their children. METHODS: Intensive steady-state 24-hour pharmacokinetic profiles were performed after administration of 300 mg of atazanavir and 150 mg of cobicistat orally in fixed-dose combination once daily during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Atazanavir and cobicistat were measured in plasma by validated high-performance liquid chromatography-ultraviolet and liquid chromatography-tandem mass spectrometry assays, respectively. A 2-tailed Wilcoxon signed-rank test (α = 0.10) was used for paired within-participant comparisons. RESULTS: A total of 11 pregnant women enrolled in the study. Compared with paired postpartum data, atazanavir AUC0-24 was 26% lower in the second trimester [n = 5, P = 0.1875, geometric mean of ratio (GMR) = 0.739, 90% CI: 0.527 to 1.035] and 54% lower in the third trimester (n = 6, GMR = 0.459, P = 0.1563, 90% CI: 0.190 to 1.109), whereas cobicistat AUC0-24 was 35% lower in the second trimester (n = 5, P = 0.0625, GMR = 0.650, 90% CI: 0.493 to 0.858) and 52% lower in the third trimester (n = 7, P = 0.0156, GMR = 0.480, 90% CI: 0.299 to 0.772). The median (interquartile range) 24-hour atazanavir trough concentration was 0.21 µg/mL (0.16-0.28) in the second trimester, 0.21 µg/mL (0.11-0.56) in the third trimester, and 0.61 µg/mL (0.42-1.03) in postpartum. Placental transfer of atazanavir and cobicistat was limited. CONCLUSIONS: Standard atazanavir/cobicistat dosing during pregnancy results in lower exposure which may increase the risk of virologic failure and perinatal transmission.
Assuntos
Sulfato de Atazanavir/farmacocinética , Infecções por HIV , Inibidores da Protease de HIV , Complicações Infecciosas na Gravidez , Fármacos Anti-HIV , Sulfato de Atazanavir/uso terapêutico , Criança , Cobicistat , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Transmissão Vertical de Doenças Infecciosas , Placenta , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estudos ProspectivosRESUMO
BACKGROUND: Tenofovir alafenamide (TAF) is a key component of HIV treatment, but pharmacokinetic data supporting the use of TAF during pregnancy are limited. In this study, we report pharmacokinetic, safety, and birth outcomes for TAF 25 mg with a boosted protease inhibitor in pregnant women living with HIV. METHODS: IMPAACT P1026s was a multicenter, nonrandomized, open-label, phase IV prospective study. Pregnant women living with HIV receiving TAF 25 mg with a boosted protease inhibitor were eligible. Intensive pharmacokinetic assessments were performed during the second and third trimesters and 6-12 weeks postpartum. Maternal and cord blood samples were collected at delivery. Infant washout samples were collected through 5-9 days postbirth. Comparisons of paired pharmacokinetic data between pregnancy and postpartum were made using geometric mean ratios (GMR) [90% confidence intervals (CIs)] and Wilcoxon signed-rank tests with P < 0.10 considered significant. RESULTS: Twenty-nine women were enrolled from the United States (median age 31 years and weight 84.5 kg during the third trimester; 48% Black, 45% Hispanic/Latina). TAF AUCtau did not significantly differ in the second [GMR 0.62 (90% CI: 0.29 to 1.34); P = 0.46] or third trimester [GMR 0.94 (90% CI: 0.63 to 1.39); P = 0.50] vs. postpartum and were comparable with historical data in nonpregnant adults. TAF was only quantifiable in 2/25 maternal delivery samples and below the limit of quantification in all cord blood and infant washout samples, likely because of the short half-life of TAF. CONCLUSION: TAF AUCtau did not significantly differ between pregnancy and postpartum. These findings provide reassurance as TAF use during pregnancy continues to expand.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Complicações Infecciosas na Gravidez , Adenina/uso terapêutico , Adulto , Alanina , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/uso terapêutico , Antivirais/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estudos Prospectivos , Inibidores de Proteases/uso terapêutico , Tenofovir/análogos & derivadosRESUMO
OBJECTIVE: To evaluate darunavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery. DESIGN: Nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of darunavir and cobicistat pharmacokinetics in pregnant women with HIV and their children in the United States. METHODS: Intensive steady-state 24-h pharmacokinetic profiles were performed after administration of 800âmg of darunavir and 150âmg of cobicistat orally in fixed dose combination once-daily during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Darunavir and cobicistat were measured in plasma by validated HPLC-UV and liquid chromatography with tandem mass spectrometry detection (LC-MS)/MS assays, respectively. A two-tailed Wilcoxon signed-rank test (αâ=â0.10) was employed for paired within-participant comparisons. RESULTS: A total of 29 pregnant women receiving darunavir and cobicistat once-daily enrolled in the study. Compared with paired postpartum data, darunavir AUC0--24 was 53% lower in the second trimester [nâ=â12, Pâ=â0.0024, geometric mean of ratio (GMR)=0.47, 90% confidence interval (CI) 0.33 - 0.68] and 56% lower in the third trimester (nâ=â18, Pâ<â0.0001, GMRâ=â0.44, 90% CI 0.36 - 0.54), whereas cobicistat AUC0--24 was 50% lower in the second trimester (nâ=â12, Pâ=â0.0024, GMRâ=â0.50, 90% CI 0.36-0.69) and 56% lower in the third trimester (nâ=â18, Pâ<â0.0001, GMRâ=â0.44, 90% CI 0.35-0.55). Placental transfer of darunavir and cobicistat was limited. CONCLUSION: Standard darunavir/cobicistat dosing during pregnancy results in significantly lower exposure during pregnancy, which may increase the risk of virologic failure and perinatal transmission.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Fármacos Anti-HIV/uso terapêutico , Criança , Cobicistat/uso terapêutico , Darunavir/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Transmissão Vertical de Doenças Infecciosas , Placenta , Período Pós-Parto , Gravidez , Estudos ProspectivosRESUMO
OBJECTIVE: To evaluate the pharmacokinetics of tenofovir alafenamide (TAF) 10âmg with cobicistat and 25âmg without boosting in pregnant and postpartum women with HIV and to characterize TAF placental transfer and infant washout pharmacokinetics. DESIGN: Open-label, multicenter phase IV prospective study of TAF pharmacokinetics during pregnancy, postpartum, delivery, and infant washout. METHODS: Pregnant women receiving TAF 10âmg with cobicistat or TAF 25âmg without boosting as part of clinical care had intensive pharmacokinetic assessments performed during the second and third trimesters, and 6-12 weeks postpartum. Maternal and cord blood samples were collected at delivery, and washout pharmacokinetic samples were collected in infants. TAF concentrations were quantified using liquid chromatography/mass spectrometry. Comparisons between pregnancy and postpartum were made using geometric mean ratios (90% confidence intervals) and Wilcoxon signed-rank tests. RESULTS: Thirty-one pregnant women receiving TAF 10âmg with cobicistat-boosting and 27 women receiving TAF 25âmg without boosting were enrolled. TAF exposures did not significantly differ between pregnancy and postpartum when administered as 10âmg with cobicistat. Antepartum TAF exposures with the 25âmg dose were 33-43% lower in comparison with postpartum, but comparable with those measured in nonpregnant adults. TAF was below the lower limit of quantitation in 43 of 44 cord blood, 41 of 45 maternal blood at delivery, and all infant washout samples. CONCLUSION: TAF exposures were comparable or higher than those measured in nonpregnant adults during pregnancy and postpartum. These findings provide reassurance on adequate TAF exposures during pregnancy, and support efforts to expand the use of TAF in pregnant women with HIV.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adenina/análogos & derivados , Adulto , Alanina , Fármacos Anti-HIV/uso terapêutico , Cobicistat/uso terapêutico , Emtricitabina/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Período Pós-Parto , Gravidez , Estudos Prospectivos , Tenofovir/análogos & derivadosRESUMO
AIM: To identify risk factors associated with and evaluate algorithms for predicting Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) cervical infections in women attending family planning clinics in Thailand. METHODS: Eligible women were recruited from family planning clinics from all regions in Thailand. The women were followed at 3-month intervals for 15-24 months. At each visit, the women were interviewed for interval sexually transmitted infection (STI) history in the past 3 months, recent sexual behavior, and contraceptive use. Pelvic examinations were performed and endocervical specimens were collected to test for CT and NG using polymerase chain reaction. RESULTS: Factors associated with incident CT/NG cervical infections in multivariate analyses included region of country other than the north, age Assuntos
Infecções por Chlamydia/epidemiologia
, Chlamydia trachomatis/isolamento & purificação
, Gonorreia/epidemiologia
, Programas de Rastreamento/métodos
, Neisseria gonorrhoeae/isolamento & purificação
, Doenças do Colo do Útero/epidemiologia
, Adolescente
, Adulto
, Algoritmos
, Instituições de Assistência Ambulatorial/estatística & dados numéricos
, Colo do Útero/microbiologia
, Infecções por Chlamydia/microbiologia
, Epitélio/microbiologia
, Feminino
, Gonorreia/microbiologia
, Humanos
, Valor Preditivo dos Testes
, Fatores de Risco
, Tailândia/epidemiologia
, Doenças do Colo do Útero/microbiologia
, Adulto Jovem
RESUMO
BACKGROUND: An association has been demonstrated between herpes simplex type 2 (HSV-2) and HIV infection among men, but prospective studies in women have yielded mixed results. OBJECTIVE: To estimate the effects of prevalent and incident HSV-2 infection on subsequent HIV acquisition among women in two African countries. DESIGN: Prospective cohort study. METHODS: HSV-2 and HIV serostatus were evaluated at enrollment and quarterly for 15-24 months among 4531 sexually active, HIV-uninfected women aged 18-35 years from Uganda and Zimbabwe. The association between prior HSV-2 infection and HIV acquisition was estimated using a marginal structural discrete survival model, adjusted for covariates. RESULTS: HSV-2 seroprevalence at enrollment was 52% in Uganda and 53% in Zimbabwe; seroincidence during follow-up was 9.6 and 8.8/100 person-years in Uganda and Zimbabwe, respectively. In Uganda, the hazard ratio (HR) for HIV was 2.8 [95% confidence interval (CI), 1.5-5.3] among women with seroprevalent HSV-2 and 4.6 (95% CI, 1.6-13.1) among women with seroincident HSV-2, adjusted for confounding. In Zimbabwe, the HR for HIV was 4.4 (95% CI, 2.7-7.2) among women with seroprevalent HSV-2, and 8.6 (95% CI, 4.3-17.1) among women with seroincident HSV-2, adjusted for confounding. The population attributable risk percent for HIV due to prevalent and incident HSV-2 infection was 42% in Uganda and 65% in Zimbabwe. CONCLUSIONS: HSV-2 plays an important role in the acquisition of HIV among women. Efforts to implement known HSV-2 control measures, as well as identify additional measures to control HSV-2, are urgently needed to curb the spread of HIV.
Assuntos
Infecções por HIV/virologia , Herpes Genital/complicações , Adolescente , Adulto , Métodos Epidemiológicos , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Herpes Genital/epidemiologia , Humanos , Comportamento Sexual , Uganda/epidemiologia , Zimbábue/epidemiologiaRESUMO
BACKGROUND: Rilpivirine pharmacokinetics is defined by its absorption, distribution, metabolism, and excretion. Pregnancy can affect these factors by changes in cardiac output, protein binding, volume of distribution, and cytochrome P450 (CYP) 3A4 activity. Rilpivirine is metabolized by CYP3A4. The impact of pregnancy on rilpivirine pharmacokinetics is largely unknown. METHODS: International Maternal Pediatric Adolescent AIDS Clinical Trials P1026s is a multicenter, nonblinded, prospective study evaluating antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving rilpivirine 25 mg once daily as part of their combination antiretrovirals for clinical care. Thirty-two women were enrolled in this study. Intensive pharmacokinetic sampling was performed at steady state during the second trimester, the third trimester, and postpartum. Maternal and umbilical cord blood samples were obtained at delivery. Plasma rilpivirine concentration was measured using liquid chromatography-mass spectrometry; lower limit of quantitation was 10 ng/mL. RESULTS: Median (range) AUC0-24 were 1969 (867-4987, n = 15), 1669 (556-4312, n = 28), and 2387 (188-6736, n = 28) ng·h/mL in the second trimester, the third trimester, and postpartum, respectively (P < 0.05 for either trimester vs postpartum). Median (range) C24 were 63 (37-225, n = 17), 56 (<10-181, n = 30), and 81 (<10-299, n = 28) ng/mL (P < 0.05 for either trimester vs postpartum). High variability in pharmacokinetic parameters was observed between subjects. Median (range) cord blood/maternal concentration ratio was 0.55 (0.3-0.8, n = 21). Delivery HIV-1 RNA was ≤50 copies per milliliter in 70% and ≤400 copies per milliliter in 90% of women. Cmin were significantly lower at 15 visits with detectable HIV-1 RNA compared with 61 visits with undetectable HIV-1 RNA, 29 (<10-93) vs 63 (15-200) ng/mL (P = 0.0001). Cmin was below the protein binding-adjusted EC90 concentration (12.2 ng/mL) at 4 visits in 3 of 31 women (10%). CONCLUSIONS: Rilpivirine exposure is lower during pregnancy compared with postpartum and highly variable. Ninety percent of women had minimum concentrations above the protein binding-adjusted EC90 for rilpivirine.
Assuntos
Fármacos Anti-HIV/farmacocinética , Infecções por HIV/sangue , Inibidores da Protease de HIV/farmacocinética , Complicações Infecciosas na Gravidez/sangue , Rilpivirina/farmacocinética , Adolescente , Adulto , Fármacos Anti-HIV/sangue , Citocromo P-450 CYP3A/sangue , Feminino , Sangue Fetal/química , Seguimentos , Inibidores da Protease de HIV/sangue , Humanos , Recém-Nascido , Período Pós-Parto , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Rilpivirina/sangue , Resultado do Tratamento , Adulto JovemRESUMO
Reports on HIV infection and risk behaviors among female drug users in developing countries, particularly in Asia, are limited. In this study, we investigated HIV prevalence and risk factors for HIV infection among 200 women admitted for 21-day inpatient drug detoxification in Chiang Mai, Thailand. Volunteers completed a face-to-face interview using a structured interview, HIV pre-test counseling, specimen collection for HIV and STD tests, and were provided test results and HIV post-test counseling 1 week later. Two-third of participants (68%) were ethnic minorities with no formal education. Overall, 14 (7%) were HIV positive: 25% among 28 heroin injectors and 4.1% among 172 opium or methamphetamine smokers (p<0.001). History of drug injection and sexual abuse were associated with HIV infection. HIV prevention strategies for drug-using women in Thailand should consider both harm reduction strategies for drug use and promoting safer sex measures in a culturally appropriate context.
Assuntos
Soropositividade para HIV/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , Estimulantes do Sistema Nervoso Central , Etnicidade , Feminino , Humanos , Metanfetamina , Entorpecentes , Ópio , Fumar , Abuso de Substâncias por Via Intravenosa/epidemiologia , Tailândia/epidemiologiaRESUMO
Alu elements and long interspersed element-1 (LINE-1 or L1) are two major human intersperse repetitive sequences. Lower Alu methylation, but not LINE-1, has been observed in blood cells of people in old age, and in menopausal women having lower bone mass and osteoporosis. Nevertheless, Alu methylation levels also vary among young individuals. Here, we explored phenotypes at birth that are associated with Alu methylation levels in young people. In 2010, 249 twenty-years-old volunteers whose mothers had participated in a study association between birth weight (BW) and nutrition during pregnancy in 1990, were invited to take part in our present study. In this study, the LINE-1 and Alu methylation levels and patterns were measured in peripheral mononuclear cells and correlated with various nutritional parameters during intrauterine and postnatal period of offspring. This included the amount of maternal intake during pregnancy, the mother's weight gain during pregnancy, birth weight, birth length, and the rate of weight gain in the first year of life. Catch-up growth (CUG) was defined when weight during the first year was >0.67 of the standard score, according to WHO data. No association with LINE-1 methylation was identified. The mean level of Alu methylation in the CUG group was significantly higher than those non-CUG (39.61% and 33.66 % respectively, P < 0.0001). The positive correlation between the history of CUG in the first year and higher Alu methylation indicates the role of Alu methylation, not only in aging cells, but also in the human growth process. Moreover, here is the first study that demonstrated the association between a phenotype during the newborn period and intersperse repetitive sequences methylation during young adulthood.
Assuntos
Elementos Alu/genética , Peso ao Nascer/genética , Adulto , Feminino , Humanos , Elementos Nucleotídeos Longos e Dispersos/genética , Metilação , Osteoporose/genética , Gravidez , Adulto JovemRESUMO
OBJECTIVE: To describe darunavir (DRV) pharmacokinetics with once-and twice-daily dosing during pregnancy and postpartum in HIV-infected women. DESIGN: Women were enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials Network Protocol P1026s, a prospective nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included separate cohorts receiving DRV/ritonavir dosed at either 800 mg/100 mg once daily or 600 mg/100 mg twice daily. METHODS: Intensive steady-state 12- or 24-hour pharmacokinetic profiles were performed during the second trimester, third trimester, and postpartum. DRV was measured using high-performance liquid chromatography (detection limit: 0.09 µg/mL). RESULTS: Pharmacokinetic data were available for 64 women (30 once daily and 34 twice daily dosing). Median DRV area under the concentration-time curve (AUC) and maximum concentration were significantly reduced during pregnancy with both dosing regimens compared with postpartum, whereas the last measurable concentration (Clast) was also reduced during pregnancy with once daily DRV. DRV AUC with once daily dosing was reduced by 38% during the second trimester and by 39% during the third trimester. With twice daily dosing, DRV AUC was reduced by 26% in both trimesters. The median (range) ratio of cord blood/maternal delivery DRV concentration in 32 paired samples was 0.18 (range: 0-0.82). CONCLUSIONS: DRV exposure is reduced by pregnancy. To achieve DRV plasma concentrations during pregnancy equivalent to those seen in nonpregnant adults, an increased twice daily dose may be necessary. This may be especially important for treatment-experienced women who may have developed antiretroviral resistance mutations.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Infecções por HIV/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacocinética , Adolescente , Adulto , Cromatografia Líquida de Alta Pressão , Estudos de Coortes , Darunavir , Feminino , Humanos , Plasma/química , Gravidez , Estudos Prospectivos , Ritonavir/administração & dosagem , Ritonavir/farmacocinética , Adulto JovemRESUMO
Cross-sectional laboratory data were used to model the patterns of total lymphocyte count and lymphocyte subpopulation counts among persons with chronic HIV-1 subtype E (CRF01_AE) infection during the 6.5 years preceding death. The data cover 331 HIV-infected decedents from a heterosexual HIV transmission study of 590 northern Thai couples enrolled in 1992-1998. From blood collected at enrollment, the lymphocyte phenotypes (CD3, CD8, CD4, natural killer, and B cells) were stained using two-color monoclonal antibody combinations and quantified by flow cytometry. Piecewise linear splines modeled the associations between lymphocyte levels and time before death. Mean CD3, CD8, and B cell levels showed no temporal associations from 6.5 to 2 years before death, but each declined significantly during the 2 years before death. CD3 levels declined 31.0% [95% confidence interval (-40.3%, -19.8%)] and CD8 levels declined 24.6% (-35.4%, -13.5%) annually in the 2 years prior to death. In contrast, CD4 and NK cell levels declined little from 6.5 to 4.5 years before death but declined significantly over the 4.5 years prior to death. CD4 levels declined 22.1% (-29.2%, -12.0%) annually from 4.5 to 2 years prior to death and 63.7% (-72.3%, -53.6%) annually over the remaining 2 years. Similar lymphocyte patterns have been reported in U. S. and European populations with HIV-1 subtype B infection.
Assuntos
Infecções por HIV/imunologia , HIV-1 , Subpopulações de Linfócitos/imunologia , Adolescente , Adulto , Linfócitos B/imunologia , Complexo CD3/análise , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Citometria de Fluxo , Genótipo , HIV-1/classificação , HIV-1/genética , Humanos , Imunofenotipagem , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Coloração e Rotulagem , TailândiaRESUMO
CRF01_AE and subtype B have dominated the HIV-1 epidemic in Thailand since 1989. We reported a new circulating recombinant form of HIV-1, CRF15_01B, as well as other unique CRF01_AE/B recombinants among prevalent HIV infections in Thailand. We sought to study this challenging molecular picture through assessment of subtypes among recent HIV-1 seroconverters in northern Thai drug users. A total of 847 HIV-1 seronegative drug users (342 IDU and 505 non-IDU) were enrolled, from 1999 to 2002, in a prospective study; 39 HIV-1 incident cases were identified and characteristics were collected. The overall HIV-1 incidence rate was 2.54/100PY, but it was 10.0/100PY among male IDU. HIV was strongly associated with injection history; 38 of 39 seroconverters gave a history of IDU. A near full-length genome of HIV-1 was recovered by PCR amplification and sequenced from peripheral mononuclear cell extracted DNA of 38 seroconverters. Phylogenetic analysis revealed that 33 (86.8%) were CRF01_AE and 5 (13.2%) were CRF01_AE/B recombinants. These recombinants had different structure but shared some common breakpoints, indicating an ongoing recombination process. Recombinant infection increased with year of sampling (0 to 57.1%). The molecular epidemiology of HIV-1 among drug users in northern Thailand has thus entered a new era. CRF01_AE remains predominant while pure subtype B is becoming rare, and now a substantial component of the epidemic. These findings support the need for CRF01_AE and subtype B components in clade-matched vaccine strategies for Thai phase III trials. Ongoing molecular surveillance of circulating HIV-1 strains is imperative for the evaluation of HIV vaccine efficacy.
Assuntos
Infecções por HIV/complicações , Infecções por HIV/epidemiologia , HIV-1/genética , Epidemiologia Molecular , Abuso de Substâncias por Via Intravenosa/complicações , Sequência de Bases , Primers do DNA , Feminino , Infecções por HIV/virologia , Humanos , Masculino , Recombinação Genética , TailândiaRESUMO
HIV-1 CRF.AE-01 (formerly subtype E) infection is highly prevalent in Southeast Asia. Despite success with public health measures, the development of an effective CRF01.AE vaccine is critical to the control of this epidemic. Sera from the open-label arms of the first clinical trial of a bivalent HIV gp120 SF2/CM235 (subtypes B and CRF.AE-01, respectively) vaccine were evaluated for the presence of gp120-specific binding (BAb) and neutralizing antibody (NAb). Twelve pre- and postvaccination sera pairs were tested for CM235 BAb; anti-gp120 CM235 BAb was found in all postvaccination samples. The 12 pre- and postvaccination (1 month after third vaccination) serum pairs were evaluated in several neutralization formats: heterologous T cell line adapted (TCLA) NP03/H9, homologous CM235/PBMC, CM235/dendritic cell, and CM235M4-C4.6/A3R5. A3R5 is a CCR5+ T cell line, and CM235M4-C4.6 is the homologous CM235 virus adapted to growth in A3R5 cells. All volunteers developed BAb, but meaningful NAb was not demonstrable against primary isolate CM235. Using the TCLA CRF01.AE virus NP03 in H9 cells, 9 of 12 persons had NAb with a geometric mean titer (GMT) of 46. The CM235M4-C4.6 virus in A3R5 cells also detected NAb in 9 of 12 persons, with a GMT of 41. CM235M4-C4.6/A3R5 detected NAb in two persons with negligible NAb to NP03/H9 and vice versa. Whether the NAb detected by the CM235M4-C4.6/A3R5 system is qualitatively different from those in more traditional NP03/H9 assays will require further study.
Assuntos
Vacinas contra a AIDS/imunologia , Anticorpos Anti-HIV/sangue , Proteína gp120 do Envelope de HIV/imunologia , HIV-1/imunologia , Sequência de Aminoácidos , Método Duplo-Cego , HIV-1/classificação , Humanos , Dados de Sequência Molecular , Testes de Neutralização , Receptores CCR5/análise , VacinaçãoRESUMO
Several CD4 lymphocyte enumeration methods have been developed to be used as alternatives to conventional flow cytometry. However, no consensus has been reached on which technique should be widely adopted. We introduce here a novel nonflow cytometric method, called CD4 Select, for enumeration of CD4 lymphocytes. Instead of using a flow cytometer, the method requires only an automatic hematoanalyzer (complete blood count [CBC] machine). The correlations of the percentage of CD4 lymphocytes and absolute CD4 counts with the CD4 Select method and standard flow cytometry were 0.932 and 0.922, respectively. The CD4 Select method yielded percentage of CD4 lymphocytes greater than flow cytometry by a mean of 0.06%, and the limits of agreement at 95% confidence interval (CI) were 9.46% to -9.56% using Bland-Altman analysis. The CD4 select method is cheap, valid, and simple enough to be conducted locally at small facilities. The method yields not only absolute CD4 lymphocytes, but also percentage of CD4 lymphocytes. The use of a hematoanalyzer also gives this method relatively high sample throughput and makes it less labor-intensive than other nonflow cytometric methods.
Assuntos
Contagem de Linfócito CD4/economia , Contagem de Linfócito CD4/métodos , Infecções por HIV/imunologia , Anticorpos Monoclonais/metabolismo , Citometria de Fluxo/economia , Citometria de Fluxo/métodos , HumanosRESUMO
OBJECTIVE: To determine risk factors for incident bacterial vaginosis (BV) in young Thai women. STUDY DESIGN: Prospective data from a cohort of 1522 women aged 18 to 35 years, who were enrolled in a study of hormonal contraception and HIV acquisition, were used to evaluate potential risk factors for BV, as diagnosed by Amsel criteria. RESULTS: The median prevalence of BV from 3 to 24 months of follow-up visits was 2.5%. The BV incidence was 10.0 per 100-woman years. Statistically significant factors in multivariable analysis were sex during menstruation [hazard ratio (HR), 1.80; 95% CI, 1.11-2.92], male partners having sex with other women (HR, 2.3; 95% CI, 1.45-2.98), cigarette smoking (HR, 1.79; 95% CI, 1.08-2.98), and trichomoniasis (HR, 15.68; 95% CI, 4.95-49.68). Intravaginal practices were not associated with incident BV in unadjusted or adjusted analysis. CONCLUSIONS: This study supports the association between sexual behaviors and the incident BV. Failure to detect an association between intravaginal practices and incident BV warrants further studies in high-risk populations or in women with a higher prevalence of intravaginal practices.
Assuntos
Vaginose Bacteriana/epidemiologia , Vaginose Bacteriana/prevenção & controle , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Incidência , Prevalência , Estudos Prospectivos , Fatores de Risco , Comportamento Sexual , Fatores Socioeconômicos , Tailândia/epidemiologia , Vaginose Bacteriana/etiologiaRESUMO
HIV voluntary counseling and testing (VCT), an important strategy for HIV prevention and care, has been available in all government hospitals in Thailand since 1992. We assessed factors associated with HIV testing, its uptake, and estimates of HIV incidence after HIV testing among male northern Thai injecting drug users (IDUs) admitted for inpatient drug treatment. Participants were interviewed about risk behaviors and HIV testing history before VCT was provided as part of the study. Of 825 IDUs who participated, 36% reported a prior HIV test. Factors associated with prior HIV testing in multiple logistic regression analysis included higher education and having >1 lifetime sex partner. Needle sharing was not associated with prior HIV testing. Of the 298 men with a prior test, 80% reported a negative result on their last prior HIV test, of whom 28% tested positive in our study, leading to an estimated incidence rate of 10.2 per 100 person-years. Fifty-nine percent of the IDUs who reported a prior HIV test stated that they did not receive pre- and/or posttest counseling. HIV incidence among IDUs remains high despite having VCT. Extending HIV prevention and harm reduction programs is urgently needed for IDUs in the region.
Assuntos
Infecções por HIV/epidemiologia , Abuso de Substâncias por Via Intravenosa , Sorodiagnóstico da AIDS/estatística & dados numéricos , Adulto , Estudos Transversais , Aconselhamento Diretivo/estatística & dados numéricos , Programas Governamentais/estatística & dados numéricos , Infecções por HIV/prevenção & controle , Humanos , Incidência , Masculino , Avaliação de Programas e Projetos de Saúde , Fatores de Risco , Comportamento Sexual , Centros de Tratamento de Abuso de Substâncias , Inquéritos e Questionários , Tailândia/epidemiologiaRESUMO
A barrier to the appropriate provision of antiretroviral therapy to treat immunosuppressed HIV-infected persons in resource-poor countries is identifying who requires treatment. The World Health Organization (WHO) has suggested using a clinical algorithm combined with a total lymphocyte count (TLC) < 1200 cells/mm as a surrogate for a CD4 count less than 200 cells/mm when it is not possible to measure the CD4 count. We evaluated various TLC levels, anemia, and body mass index and compared our data with the WHO criteria to develop a more sensitive algorithm to predict CD4 counts of < 200 cells/mm and < 350 cells/mm in 839 men and women from Thailand infected with HIV-1 subtype E (CRF01_AE). The December 2003 WHO guidelines had a sensitivity of 34.1% in men and 31.8% in women to detect persons with a CD4 count < 200 cells/mm in this HIV-infected population from Thailand. The use of a TLC < 1500 cells/mm or TLC < 2000 cells/mm combined with anemia or WHO stage II infection doubled the sensitivity to detect persons with a CD4 count < 200 (63.0% in men, 68.2% in women) with less than a 6% decrease in specificity.
Assuntos
Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/imunologia , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Alocação de Recursos para a Atenção à Saúde , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Algoritmos , Fármacos Anti-HIV/economia , Custos e Análise de Custo , Feminino , Humanos , Contagem de Linfócitos , Masculino , Sensibilidade e Especificidade , Caracteres Sexuais , TailândiaRESUMO
The authors sought to determine sociodemographic and sexual and drug use risk factors for HIV infection among drug users in northern Thailand adjacent to the Golden Triangle. The authors enrolled patients admitted for inpatient drug detoxification at one treatment center in northern Thailand and studied HIV risks and prevalence using an interviewer-administered questionnaire and serum collection with HIV pretest and posttest counseling. Between February 1, 1999 and January 31, 2000, 1865 patients admitted for opiate and methamphetamine dependence completed study procedures. Overall HIV prevalence was 10.3%: 30.0% among 513 injection drug users (IDUs) and 2.8% among non-IDUs (OR = 14.8, 95% CI: 10.2, 21.6). HIV seroprevalence was 2.4% among exclusive methamphetamine users (98% of whom are non-IDUs) and 3.4% among opium smokers. Injection drug use was the dominant risk factor in multivariate models. Although Thailand is widely recognized as having a successful national response to the heterosexual HIV epidemic, seroprevalence in IDUs remains high. Despite a sharp increase of non-IDUs admitted to the drug treatment center, HIV infection and risks remained high among IDUs in northern Thailand. HIV prevention campaigns need to focus on IDUs and to implement harm reduction strategies to reduce transmission to IDUs and further contain the HIV epidemic in Thailand.