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2.
Lancet ; 372(9635): 300-13, 2008 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-18657709

RESUMO

BACKGROUND: UNICEF/WHO recommends that infants born to HIV-infected mothers who do not have access to acceptable, feasible, affordable, sustainable, and safe replacement feeding should be exclusively breastfed for at least 6 months. The aim of three trials in Ethiopia, India, and Uganda was to assess whether daily nevirapine given to breastfed infants through 6 weeks of age can decrease HIV transmission via breastfeeding. METHODS: HIV-infected women breastfeeding their infants were eligible for participation. Participants were randomly assigned to receive either single-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborns after birth) or 6 week extended-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborn babies after birth plus nevirapine 5 mg daily from days 8-42 for the infant). The randomisation sequences were generated by computer at a central data coordinating centre. The primary endpoint was HIV infection at 6 months of age in infants who were HIV PCR negative at birth. Analyses were by modified intention to treat, excluding infants with missing specimens and those with indeterminate or confirmed HIV infection at birth. These studies are registered with ClinicalTrials.gov, numbers NCT00074399, NCT00061321, and NCT00639938. FINDINGS: 2024 liveborn infants randomised in the study had at least one specimen tested before 6 months of age (1047 infants in the single-dose group and 977 infants in the extended-dose group). The modified intention-to-treat population included 986 infants in the single-dose group and 901 in the extended-dose group. At 6 months, 87 children in the single-dose group and 62 in the extended-dose group were infected with HIV (relative risk 0.80, 95% CI 0.58-1.10; p=0.16). At 6 weeks of age, 54 children in the single-dose group and 25 in the extended-dose group were HIV positive (0.54, 0.34-0.85; p=0.009). 393 infants in the single-dose group and 346 in the extended-dose group experienced grade 3 or 4 serious adverse events during the study (p=0.54). INTERPRETATION: Although a 6-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at 6 weeks of age, the lack of a significant reduction in the primary endpoint-risk of HIV transmission at 6 months-suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high. FUNDING: US National Institutes of Health; US National Institute of Allergy and Infectious Diseases; Fogarty International Center.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Aleitamento Materno/efeitos adversos , Infecções por HIV/prevenção & controle , Nevirapina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Esquema de Medicação , Etiópia , Feminino , Infecções por HIV/etiologia , Humanos , Índia , Lactente , Recém-Nascido , Masculino , Estudos Multicêntricos como Assunto , Nevirapina/administração & dosagem , Nevirapina/efeitos adversos , Gravidez , Uganda
3.
Contraception ; 77(6): 410-4, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18477489

RESUMO

BACKGROUND: Progestin-only injectable contraceptives continue to gain in popularity, but uncertainty remains about pregnancy risk among women late for reinjection. The World Health Organization (WHO) recommends a "grace period" of 2 weeks after the scheduled 13-week reinjection. Beyond 2 weeks, however, many providers send late clients home to await menses. STUDY DESIGN: A prospective cohort study in Uganda, Zimbabwe and Thailand followed users of depot-medroxyprogesterone acetate (DMPA) for up to 24 months. Users were tested for pregnancy at every reinjection, allowing analysis of pregnancy risk among late comers. RESULTS: The analysis consists of 2290 participants contributing 13,608 DMPA intervals. The pregnancy risks per 100 women-years for "on time" [0.6; 95% confidence interval (CI), 0.33-0.92], "2-week grace" (0.0; 95% CI, 0.0-1.88) and "4-week grace" (0.4; 95% CI, 0.01-2.29) injections were low and virtually identical. CONCLUSION: Extending the current WHO grace period for DMPA reinjection from 2 to 4 weeks does not increase pregnancy risk and could increase contraceptive continuation.


Assuntos
Anticoncepcionais Femininos/administração & dosagem , Medroxiprogesterona/administração & dosagem , Taxa de Gravidez , Adulto , Estudos de Coortes , Comportamento Contraceptivo , Esquema de Medicação , Feminino , Humanos , Injeções Intramusculares , Gravidez , Estudos Prospectivos , Tailândia , Resultado do Tratamento , Uganda , Zimbábue
4.
AIDS ; 21(12): 1515-23, 2007 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-17630545

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/epidemiologia
5.
AIDS ; 21(13): 1779-89, 2007 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-17690577

RESUMO

OBJECTIVE: To assess whether male circumcision of the primary sex partner is associated with women's risk of HIV. DESIGN: Data were analyzed from 4417 Ugandan and Zimbabwean women participating in a prospective study of hormonal contraception and HIV acquisition. Most were recruited from family planning clinics; some in Uganda were referred from higher-risk settings such as sexually transmitted disease clinics. METHODS: Using Cox proportional hazards models, time to HIV acquisition was compared for women with circumcised or uncircumcised primary partners. Possible misclassification of male circumcision was assessed using sensitivity analysis. RESULTS: At baseline, 74% reported uncircumcised primary partners, 22% had circumcised partners and 4% had partners of unknown circumcision status. Median follow-up was 23 months, during which 210 women acquired HIV (167, 34, and 9 women whose primary partners were uncircumcised, circumcised, or of unknown circumcision status, respectively). Although unadjusted analyses indicated that women with circumcised partners had lower HIV risk than those with uncircumcised partners, the protective effect disappeared after adjustment for other risk factors [hazard ratio (HR), 1.03; 95% confidence interval (CI), 0.69-1.53]. Subgroup analyses suggested a non-significant protective effect of male circumcision on HIV acquisition among Ugandan women referred from higher-risk settings: adjusted HR 0.16 (95% CI, 0.02-1.25) but little effect in Ugandans (HR, 1.33; 95% CI, 0.72-2.47) or Zimbabweans (HR, 1.12; 95% CI, 0.65-1.91) from family planning clinics. CONCLUSIONS: After adjustment, male circumcision was not significantly associated with women's HIV risk. The potential protection offered by male circumcision for women recruited from high-risk settings warrants further investigation.


Assuntos
Circuncisão Masculina/estatística & dados numéricos , Infecções por HIV/prevenção & controle , Adolescente , Adulto , Países em Desenvolvimento , Métodos Epidemiológicos , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Humanos , Masculino , Comportamento Sexual , Uganda/epidemiologia , Zimbábue/epidemiologia
6.
AIDS ; 21(1): 85-95, 2007 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-17148972

RESUMO

BACKGROUND: Combined oral contraceptives (COC) and depot-medroxyprogesterone acetate (DMPA) are among the most widely used family planning methods; their effect on HIV acquisition is not known. OBJECTIVE: To evaluate the effect of COC and DMPA on HIV acquisition and any modifying effects of other sexually transmitted infections. METHODS: This multicenter prospective cohort study enroled 6109 HIV-uninfected women, aged 18-35 years, from family planning clinics in Uganda, Zimbabwe and Thailand. Participants received HIV testing quarterly for 15-24 months. The risk of HIV acquisition with different contraceptive methods was assessed (excluding Thailand, where there were few HIV cases). RESULTS: HIV infection occurred in 213 African participants (2.8/100 woman-years). Use of neither COC [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.69-1.42] nor DMPA (HR, 1.25; 95% CI, 0.89-1.78) was associated with risk of HIV acquisition overall, including among participants with cervical or vaginal infections. While absolute risk of HIV acquisition was higher among participants who were seropositive for herpes simplex virus 2 (HSV-2) than in those seronegative at enrolment, among the HSV-2-seronegative participants, both COC (HR, 2.85; 95% CI, 1.39-5.82) and DMPA (HR, 3.97; 95% CI, 1.98-8.00) users had an increased risk of HIV acquisition compared with the non-hormonal group. CONCLUSIONS: No association was found between hormonal contraceptive use and HIV acquisition overall. This is reassuring for women needing effective contraception in settings of high HIV prevalence. However, hormonal contraceptive users who were HSV-2 seronegative had an increased risk of HIV acquisition. Additional research is needed to confirm and explain this finding.


Assuntos
Anticoncepcionais Orais Hormonais , Infecções por HIV/transmissão , HIV , Acetato de Medroxiprogesterona , Adulto , Intervalos de Confiança , Comportamento Contraceptivo , Preparações de Ação Retardada , Transmissão de Doença Infecciosa , Feminino , Infecções por HIV/virologia , Herpes Simples/complicações , Herpesvirus Humano 2 , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Tailândia , Uganda , Zimbábue
7.
AIDS ; 21(15): 2077-82, 2007 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-17885298

RESUMO

OBJECTIVES: Use of single dose nevirapine (SD NVP) for prevention of HIV-1 mother-to-child transmission (pMTCT) is associated with selection of K103N-containing HIV variants. Repeat use of SD NVP for pMTCT may influence emergence and persistence of NVP-resistant variants. DESIGN: K103N-containing variants were studied in 48 Ugandan women who received SD NVP in the HIVNET 012 trial, and were re-exposed to SD NVP in one (n = 44) or two (n = 4) subsequent pregnancies during a 5-year follow-up study. METHODS: Samples were analyzed using the LigAmp assay (assay cutoff: 0.5% K103N). RESULTS: Among 44 women who were re-exposed to SD NVP in one subsequent pregnancy, 37.8% had K103N detected within 1 year of SD-NVP re-exposure. Detection of K103N was independently associated with detection of K103N 6-8 weeks after the first SD NVP exposure and with pre-NVP viral load. The portion of women with undetectable K103N by 2 years after SD NVP administration was similar after first versus second use of SD NVP for pMTCT. K103N was undetectable in 93.2% of evaluable women by 3 years of re-exposure. Only two of four women who received SD NVP in two pregnancies during the follow-up study had K103N detected after the last SD NVP exposure. CONCLUSIONS: K103N was detected in some women within 1 year of SD NVP re-exposure, but faded from detection in most women by 3 years after re-exposure. Detection of K103N by 1 year after SD NVP re-exposure was associated with prior selection of K103N-containing variants and with pre-NVP viral load.


Assuntos
Infecções por HIV/genética , HIV-1 , Nevirapina/farmacologia , Complicações Infecciosas na Gravidez/genética , Inibidores da Transcriptase Reversa/farmacologia , Farmacorresistência Viral/genética , Feminino , Seguimentos , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Nevirapina/administração & dosagem , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Inibidores da Transcriptase Reversa/administração & dosagem , Uganda , Carga Viral
8.
AIDS Res Hum Retroviruses ; 23(6): 764-8, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17604538

RESUMO

K103N is frequently detected in HIV-infected women after single dose (SD) nevirapine (NVP). K103N-containing variants were detected more frequently by the ViroSeq HIV-1 Genotyping System in women with subtype C (69.2%) than subtypes A (19.4%, p < 0.0001) or D (36.1%, p < 0.0001). K103N-containing variants were also detected more frequently and at higher levels in women with subtype C by the LigAmp assay. In this report, we analyzed samples collected prior to or within hours after SD NVP administration from antiretroviral drug-naive African women with subtypes A, C, and D. Only 1/254 samples had an NVP resistance mutation detected with the ViroSeq system, and only 4/236 samples had K103N detected at < 0.5% with the LigAmp assay [2/110 (1.8%) with subtype A, 1/46 (2.2%) with subtype C, and 1/80 (1.3%) with subtype D] (p = 0.92). We did not detect significant differences in the pre-NVP frequency of NVP resistance mutations or the pre-NVP levels of K103N-containing variants in women with subtypes A, C, and D that explain the dramatic subtype-based differences in emergence of HIV-1 variants with these mutations after SD NVP exposure.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV , HIV-1/genética , Nevirapina/farmacologia , Polimorfismo de Nucleotídeo Único/genética , África , População Negra , Análise Mutacional de DNA , Esquema de Medicação , Feminino , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , HIV-1/classificação , HIV-1/efeitos dos fármacos , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Gravidez , Complicações Infecciosas na Gravidez
9.
Obstet Gynecol ; 110(5): 1003-9, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17978111

RESUMO

OBJECTIVE: To estimate the probability of pregnancy for oral contraceptive pill (OCP), injectable contraceptive, and condom users in Uganda, Thailand, and Zimbabwe. METHODS: This study is a secondary analysis of 5,224 women who participated in a prospective study evaluating the association between hormonal contraception and human immunodeficiency virus (HIV) acquisition. RESULTS: The overall 12-month cumulative probability of pregnancy of injectable contraceptive users was 0.6% (95% confidence interval [CI] 0.3-1.0), with similar risks in Uganda (0.3%, 95% CI 0-0.7), Thailand (0.6%, 95% CI 0-1.2), and Zimbabwe (1.0%, 95% CI 0.3-1.7). The 12-month cumulative probability of pregnancy for OCP users was 9.5% (95% CI 8.1-11.0%), with similar risks of pregnancy in Uganda and Zimbabwe (14.6%, 95% CI 11.7-17.4; and 10.2%, 95% CI 8.0-12.5, respectively) but substantially lower risk in Thailand (0.5%, 95% CI 0-1.2). The overall 12-month cumulative probability of pregnancy for women intending to use a given method at baseline was 2.0% (95% CI 1.4-2.6%) for injectable contraceptives, 15.7% (95% CI 14.1-17.3%) for OCPs, and 25.8% (95% CI 23.2-28.4) for condoms. Women in Thailand experienced lower pregnancy risk with condoms (18.4%, 95% CI 11.1-25.7) than in Uganda (29.5%, 95% CI 25.7-33.4), and Zimbabwe (23.3%, 95% CI 19.4-27.2). CONCLUSION: The overall risk of pregnancy for injectable contraceptive users was substantially lower than for oral contraceptive pill users. However, Thai participants had similarly low cumulative pregnancy probabilities for both methods. Women receiving contraceptive counseling should be informed that their experience with a given method may differ from the average or typical-use pregnancy rates often discussed during contraceptive counseling. Tailored counseling is necessary for women to make informed choices. LEVEL OF EVIDENCE: II.


Assuntos
Preservativos , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Orais Combinados/uso terapêutico , Acetato de Medroxiprogesterona/administração & dosagem , Taxa de Gravidez , Adolescente , Adulto , Aconselhamento , Feminino , Humanos , Injeções Intramusculares , Estimativa de Kaplan-Meier , Gravidez , Estudos Prospectivos , Tailândia , Resultado do Tratamento , Uganda , Zimbábue
10.
AIDS ; 20(2): 217-22, 2006 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-16511414

RESUMO

BACKGROUND: To correlate nevirapine presence and concentration in cord bloods of infants born to HIV-1 infected women with report of timing of dose and HIV-1 transmission at 6 weeks of age. METHODS: All available cord blood samples from the infants of mothers enrolled in the HIVNET 012 trial who were randomly assigned to receive either nevirapine or zidovudine at the onset of labor were tested for a nevirapine concentration. RESULTS: Nevirapine was detected in the cord blood of 244 of 259 (94%) infants whose mothers reported they took nevirapine in labor more than 1 h before delivery and in 12 of 13 (92%) infants whose mothers reported they took nevirapine less than 1 h before delivery. The median nevirapine cord blood concentration was 1238 ng/ml [interquartile range (IQR), 905-1474 ng/ml] and 122 ng/ml (IQR, 64-321 ng/ml) for women who reported taking nevirapine more or less than 1 h before delivery, respectively (P < 0.001). The median nevirapine cord blood concentration of infants who were HIV-1 negative at birth, but positive at 6-8 weeks of age (n = 11), was 916 ng/ml (IQR, 737-1245 ng/ml) compared with 1192 ng/ml (IQR, 875-1471 ng/ml) for uninfected infants (n = 236). CONCLUSIONS: Cord blood nevirapine concentration correlated well with report of nevirapine administration and timing of dose before delivery. The nevirapine cord blood concentration was modestly lower in infected infants, although the number of infants infected between birth and 6-8 weeks of age was small (n = 11). The high adherence rate in the HIVNET 012 study supports the efficacy, simplicity and deliverability of this regimen.


Assuntos
Fármacos Anti-HIV/sangue , Sangue Fetal/química , Infecções por HIV/sangue , HIV-1 , Nevirapina/sangue , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Esquema de Medicação , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Troca Materno-Fetal , Nevirapina/administração & dosagem , Nevirapina/uso terapêutico , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/sangue , Inibidores da Transcriptase Reversa/uso terapêutico
11.
BMC Med Educ ; 6: 13, 2006 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-16509979

RESUMO

BACKGROUND: Cervical cancer is the commonest cancer of women in Uganda. Over 80% of women diagnosed in Mulago national referral and teaching hospital, the biggest hospital in Uganda, have advanced disease. Pap smear screening, on opportunistic rather than systematic basis, is offered free in the gynaecological outpatients clinic and the postnatal/family planning clinics. Medical students in the third and final clerkships are expected to learn the techniques of screening. Objectives of this study were to describe knowledge on cervical cancer, attitudes and practices towards cervical cancer screening among the medical workers of Mulago hospital. METHODS: In a descriptive cross-sectional study, a weighted sample of 310 medical workers including nurses, doctors and final year medical students were interviewed using a self-administered questionnaire. We measured knowledge about cervical cancer: (risk factors, eligibility for screening and screening techniques), attitudes towards cervical cancer screening and practices regarding screening. RESULTS: Response rate was 92% (285). Of these, 93% considered cancer of the cervix a public health problem and knowledge about Pap smear was 83% among respondents. Less than 40% knew risk factors for cervical cancer, eligibility for and screening interval. Of the female respondents, 65% didn't feel susceptible to cervical cancer and 81% had never been screened. Of the male respondents, only 26% had partners who had ever been screened. Only 14% of the final year medical students felt skilled enough to use a vaginal speculum and 87% had never performed a pap smear. CONCLUSION: Despite knowledge of the gravity of cervical cancer and prevention by screening using a Pap smear, attitudes and practices towards screening were negative. The medical workers who should be responsible for opportunistic screening of women they care for are not keen on getting screened themselves. There is need to explain/understand the cause of these attitudes and practices and identify possible interventions to change them. Medical students leave medical school without adequate skills to be able to effectively screen women for cervical cancer wherever they go to practice. Medical students and nurses training curricula needs review to incorporate practical skills on cervical cancer screening.


Assuntos
Atitude do Pessoal de Saúde , Competência Clínica/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Corpo Clínico Hospitalar/psicologia , Recursos Humanos de Enfermagem Hospitalar/psicologia , Teste de Papanicolaou , Estudantes de Medicina/psicologia , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal/estatística & dados numéricos , Adulto , Instituições de Assistência Ambulatorial/normas , Estudos Transversais , Feminino , Ginecologia/educação , Ginecologia/normas , Conhecimentos, Atitudes e Prática em Saúde , Hospitais de Ensino/normas , Humanos , Masculino , Programas de Rastreamento/métodos , Corpo Clínico Hospitalar/educação , Pessoa de Meia-Idade , Recursos Humanos de Enfermagem Hospitalar/educação , Padrões de Prática Médica/estatística & dados numéricos , Fatores de Risco , Inquéritos e Questionários , Uganda/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Esfregaço Vaginal/métodos
12.
AIDS ; 19(18): 2167-9, 2005 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-16284468

RESUMO

The administration of single-dose nevirapine to women in labor and their infants can prevent HIV-1 mother-to-child transmission. We examined nevirapine resistance in infants who were HIV-1 infected despite single-dose nevirapine prophylaxis, including 18 Ugandan infants (HIVNET 012 trial, nine subtype A and nine subtype D) and 23 Malawian infants (NVAZ trial, all subtype C). Nevirapine resistance was more frequent in infants with subtype C than with subtypes A and D (87 versus 50%, P = 0.016).


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/prevenção & controle , HIV-1 , Nevirapina/administração & dosagem , Complicações Infecciosas na Gravidez/prevenção & controle , Farmacorresistência Viral , Feminino , Infecções por HIV/transmissão , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Malaui , Gravidez
13.
Lancet ; 362(9387): 859-68, 2003 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-13678973

RESUMO

BACKGROUND: In 1999, we reported safety and efficacy data for short-course nevirapine from a Ugandan perinatal HIV-1 prevention trial when 496 babies were followed up to age 14-16 weeks. Safety and efficacy data are now presented for all babies followed up to 18 months of age. METHODS: From November, 1997, to April, 1999, HIV-1 infected pregnant women in Kampala, Uganda, were randomly assigned nevirapine (200 mg at labour onset and 2mg/kg for babies within 72 h of birth; regimen A) or zidovudine (600 mg orally at labour onset and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily for babies for 7 days, regimenB). Infant HIV-1 testing was done at birth, age 6-8 and 14-16 weeks, and age 12 months by HIV-1 RNA PCR, and by HIV-1 antibody at 18 months. HIV-1 transmission and HIV-1-free survival were assessed using Kaplan-Meier analysis. We recorded adverse experiences through 6-8 weeks postpartum for mothers, and 18 months for babies. Efficacy analyses were by intention to treat. FINDINGS: We enrolled 645 mothers to the study: 313 were assigned regimen A, 313 regimen B, and 19 placebo. Eight mothers were lost to follow-up before delivery. 99% of babies were breastfed (median duration 9 months). Estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were 10.3% and 8.1% at birth (p=0.35); 20.0% and 11.8% by age 6-8 weeks (p=0.0063); 22.1% and 13.5% by age 14-16 weeks (p=0.0064); and 25.8% and 15.7% by age 18 months (p=0.0023). Nevirapine was associated with a 41% (95% CI 16-59) reduction in relative risk of transmission through to age 18 months. Both regimens were well-tolerated with few serious side-effects. INTERPRETATION: Intrapartum/neonatal nevirapine significantly lowered HIV-1 transmission risk in a breastfeeding population in Uganda compared with a short intrapartum/neonatal zidovudine regimen. The absolute 8.2% reduction in transmission at 6-8 weeks was sustained at age 18 months (10.1% [95% CI 3.5-16.6]). This simple, inexpensive, well-tolerated regimen has the potential to significantly decrease HIV-1 perinatal transmission in less-developed countries.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Transmissão de Doença Infecciosa/prevenção & controle , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , HIV-1 , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Nevirapina/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Zidovudina/uso terapêutico , Adulto , Esquema de Medicação , Feminino , Seguimentos , Infecções por HIV/transmissão , Humanos , Lactente , Recém-Nascido , Início do Trabalho de Parto/efeitos dos fármacos , Gravidez , Uganda
14.
AIDS Res Hum Retroviruses ; 21(4): 319-24, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15943576

RESUMO

The HIVNET 012 trial in Uganda demonstrated that a regimen of single-dose nevirapine (NVP) can prevent HIV-1 mother-to-child transmission. Previous studies show that HIV-1 with one or more NVP resistance (NVPR) mutations can be selected in many women as early as 7 days after single-dose NVP. We evaluated the genetic linkage of NVPR mutations in plasma from women in HIVNET 012 collected 7 days after single-dose NVP administration. The HIV-1 pol region was amplified and cloned from 20 plasma samples (16 with NVPR mutations detected by population sequencing and 4 with no NVPR mutations detected), and 10 clones from each sample were sequenced. Up to five different NVPR mutations were detected in clones from a single sample. K103N and Y181C were the most common mutations detected. Clones with two genetically linked mutations were detected in four samples. Different combinations of NVPR mutations were linked in individual clones, but none of the clones contained both K103N and Y181C. Further studies are needed to evaluate whether selection of minority variants with one or more NVPR mutations after single-dose NVP is clinically relevant.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/genética , Nevirapina/farmacologia , Substituição de Aminoácidos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Feminino , Protease de HIV/genética , Transcriptase Reversa do HIV/genética , HIV-1/efeitos dos fármacos , HIV-1/isolamento & purificação , Humanos , Dados de Sequência Molecular , Mutação , Nevirapina/administração & dosagem , Nevirapina/uso terapêutico , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêutico , Análise de Sequência de DNA , Uganda
15.
Nutrition ; 21(1): 25-31, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15661475

RESUMO

OBJECTIVE: We investigated whether vitamin A supplementation would decrease mortality and morbidity rates in children infected with the human immunodeficiency virus (HIV). METHODS: We conducted a randomized, double-blind, placebo-controlled clinical trial at Mulago Hospital, a large hospital that serves the urban and semiurban populations of Kampala, Uganda. One hundred eighty-one HIV-infected children were enrolled at 6 mo and randomized to receive vitamin A supplementation, 60 mg retinol equivalent, or placebo every 3 mo from ages 15 to 36 mo. Morbidity was assessed through a 7-d morbidity history every 3 mo, and vital events were measured. Children received daily trimethoprim-sulfamethoxazole prophylactic therapy. RESULTS: After age 15 mo, children were followed for a median of 17.8 mo (interquartile range = 11.1 to 21.0 mo). The trial was stopped when there was a new policy to implement a program of mass supplementation of vitamin A in the country. Mortality rates among 87 children in the vitamin A group and 94 children in the control group were 20.6% and 32.9%, respectively, yielding a relative risk of 0.54 (95% confidence interval, 0.30 to 0.98; P = 0.044) after adjusting for baseline weight-for-height Z score. Children who received vitamin A had lower modified point prevalences of persistent cough (odds ratio, 0.47; 95% confidence interval, 0.23 to 0.96; P = 0.038) and chronic diarrhea (odds ratio, 0.48; 95% confidence interval, 0.19 to 1.18; P = 0.11) and a shorter duration of ear discharge (P = 0.03). Vitamin A supplementation had no significant effect on modified point prevalences of fever, ear discharge, bloody stools, or hospitalizations. CONCLUSIONS: Vitamin A supplementation decreases mortality rate in HIV-infected children and should be considered in the care for these children in developing countries.


Assuntos
Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Deficiência de Vitamina A/prevenção & controle , Vitamina A/administração & dosagem , Anti-Infecciosos/administração & dosagem , Pré-Escolar , Intervalos de Confiança , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Infecções por HIV/complicações , Humanos , Lactente , Masculino , Morbidade , Estado Nutricional , Fatores de Risco , Índice de Gravidade de Doença , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Uganda/epidemiologia , Vitamina A/uso terapêutico , Deficiência de Vitamina A/complicações
16.
AIDS ; 16(10): 1391-400, 2002 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-12131216

RESUMO

OBJECTIVES: To assess the safety, tolerance, pharmacokinetics, and virologic and immunologic changes associated with the use of Ugandan HIV hyperimmune globulin (HIVIGLOB) in HIV infected pregnant Ugandan women and their infants. DESIGN: A prospective, phase I/II, three-arm dose escalation trial of HIVIGLOB. METHODS: HIVIGLOB was prepared from discarded HIV infected units of blood collected from the National Blood Bank in Kampala. From June 1996 to April 1997, 31 HIV positive pregnant women were enrolled with HIVIGLOB infusions given at 37 weeks gestation and within 16 h of birth for infants. The first 10 mother-infant pairs were infused at a dose of 50 mg/kg, followed by 11 pairs at 200 mg/kg, and 10 pairs at 400 mg/kg. Study participants were followed for 30 months. RESULTS: Thirty-one women and 29 infants were infused with HIVIGLOB. The infusions were safe and well tolerated by the women and their infants at all doses. There were no significant changes in virologic or immunologic parameters after HIVIGLOB infusion. Pharmacokinetic properties of this product were similar to other immune globulin products with a median half-life of 28 days in women and 30 days in infants. CONCLUSION: An HIV immune globulin product derived from HIV infected Ugandan donors is safe, well tolerated, and has pharmacokinetic properties consistent with other immunoglobulin products. Data suggest that a 400 mg/kg dose of HIVIGLOB would be the most appropriate dose for a subsequent efficacy trial of HIVIGLOB for the prevention of mother to child HIV transmission.


Assuntos
Anticorpos Anti-HIV/administração & dosagem , Infecções por HIV/prevenção & controle , Imunoglobulinas Intravenosas/administração & dosagem , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Adulto , Feminino , Anticorpos Anti-HIV/metabolismo , Infecções por HIV/metabolismo , Meia-Vida , Humanos , Imunoglobulinas Intravenosas/farmacocinética , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , Uganda
17.
J Acquir Immune Defic Syndr ; 64(5): 464-71, 2013 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-24121753

RESUMO

OBJECTIVES: To describe 5-year growth, survival, and long-term safety among children exposed to nevirapine or zidovudine in an African perinatal prevention trial, HIVNET 012. METHODS: All study children who were alive at the age 18 months were eligible for an extended follow-up study. Children whose families consented were enrolled and evaluated every 6 months from 24 to 60 months. At each visit, history, physical examination, and growth measures were taken. From these measurements, Z scores based on World Health Organization (WHO) standards were computed. Serious adverse event data were collected. Data from the initial and extended follow-up cohorts were included in the analysis. RESULTS: Five hundred twenty-eight study children were alive at the age 18 months, and 491 (426 HIV uninfected and 65 infected) were enrolled into the follow-up study. Both exposed but uninfected children and HIV-infected children were substantially below WHO growth standards for weight and height. Head circumference Z scores for uninfected children were comparable with WHO norms. Five-year survival rates were 93% for uninfected children versus 43% for infected children. Long-term safety and growth outcomes in the 2 study arms were similar. CONCLUSIONS: Both infected and uninfected children in the 5-year HIVNET 012 follow-up showed poor height and weight growth outcomes, underscoring the need for early nutritional interventions to improve long-term growth of all infants born to HIV-infected women in resource-limited settings. Similarly, the low 5-year survival among HIV-infected children support the importance of early initiation of antiretroviral therapy. Both peripartum nevirapine and zidovudine were safe.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Quimioprevenção/métodos , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Nevirapina/uso terapêutico , Zidovudina/uso terapêutico , Antropometria , Estatura , Peso Corporal , Pré-Escolar , Feminino , Seguimentos , Infecções por HIV/transmissão , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Análise de Sobrevida
18.
J Acquir Immune Defic Syndr ; 58(4): 399-407, 2011 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-21826009

RESUMO

BACKGROUND: This phase III, randomized, clinical trial compared single-dose nevirapine (sdNVP) plus HIV hyperimmune globulin (HIVIGLOB) with sdNVP alone for preventing maternal-to-child transmission of HIV. Primary objectives were to determine rates of HIV infection among infants and to assess the safety of HIVIGLOB in combination with sdNVP in HIV-infected Ugandan pregnant women and their infants. METHODS: Mother-infant pairs were randomized to receive 200 mg of nevirapine to women in labor and 2 mg/kg NVP to newborns within 72 hours after birth (sdNVP arm) or to receive sdNVP plus a single intravenous 240-mL dose of HIVIGLOB given to women at 36- to 38-week gestation and a single intravenous 24-mL dose to newborns within 18 hours of birth (HIVIGLOB/sdNVP arm). Risk of HIV infection was determined using Kaplan-Meier and risk ratio estimates at birth, 2, 6, 14 weeks, 6, and 12 months of age. RESULTS: Intent-to-treat analysis included 198 HIVIGLOB/sdNVP and 294 sdNVP mother-infant pairs. At 6 months of age, the primary endpoint, there was no statistically significant difference in HIV transmission in the HIVIGLOB/sdNVP arm vs. the sdNVP arm [18.7% vs. 15.0%; risk ratio = 1.240 (95% confidence interval: 0.833 to 1.846); P = 0.290]. Similarly, the proportion of serious adverse events in the HIVIGLOB/sdNVP and sdNVP arms, respectively, for mothers (18.9% vs. 19.3%; P = 0.91) and infants (62.6% vs. 59.5%; P = 0.51) was not significantly different. CONCLUSIONS: Giving mother-infant pairs an infusion of peripartum HIV hyperimmune globulin in addition to sdNVP for preventing maternal-to-child transmission was as safe as sdNVP alone but was no more effective than sdNVP alone in preventing HIV transmission.


Assuntos
Infecções por HIV/transmissão , HIV-1/efeitos dos fármacos , Imunoglobulinas Intravenosas/administração & dosagem , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Adolescente , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Nevirapina/administração & dosagem , Nevirapina/efeitos adversos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/prevenção & controle , Uganda/epidemiologia , Adulto Jovem
20.
Diagn Cytopathol ; 38(8): 555-63, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19937939

RESUMO

Screening for HPV-driven cervical dysplasia and neoplasia is a significant public health concern in the developing world. The purpose of this study was to use a manual, low-cost liquid-based Pap preparation to determine HPV prevalence in HIV-positive and HIV-negative young women in Kampala, Uganda and to correlate cervical cytopathology with HPV-DNA genotype. About 196 post-partum women aged 18-30 years underwent rapid HIV testing and pelvic examination. Liquid-based cervical cytology samples were processed using a low-cost manual technique. A DNA collection device was used to collect specimens for HPV genotyping. HIV and HPV prevalence was 18 and 64%, respectively. Overall, 49% of women were infected with a high-risk HPV genotype. The most common high-risk HPV genotypes were 16 (8.2%), 33 (7.7%), 35 (6.6%), 45 (5.1%), and 58 (5.1%). The prevalence of HPV 18 was 3.6%. HIV-positive women had an HPV prevalence of 86% compared to 59% in HIV-negative women (P = 0.003). The prevalence of HPV 16/18 did not differ by HIV status. HIV-positive women were infected with a significantly greater number of HPV genotypes compared to HIV-negative women. By multivariate analysis, the main risk factor for HPV infection was coinfection with HIV. HIV-positive women were four times more likely to have abnormal cytology than HIV-negative women (43% vs. 11.6%, P < 0.001). These data highlight that HIV infection is a strong risk factor for HPV infection and resultant abnormal cervical cytology. Notably, the manual low-cost liquid-based Pap preparation is practical in this setting and offers an alternate method for local studies of HPV vaccine efficacy.


Assuntos
Alphapapillomavirus/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Esfregaço Vaginal/economia , Esfregaço Vaginal/métodos , Adolescente , Adulto , Alphapapillomavirus/genética , Colo do Útero/patologia , Colo do Útero/virologia , Demografia , Feminino , Humanos , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Prevalência , Fatores de Risco , Uganda , Adulto Jovem
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