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1.
BMJ Sex Reprod Health ; 46(1): 8-16, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31919239

RESUMO

OBJECTIVE: To update a 2016 systematic review on hormonal contraception use and HIV acquisition. METHODS: We searched Pubmed and Embase between 15 January 2016 and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using a hormonal contraceptive method and either non-users or users of another specific hormonal contraceptive method. We extracted information from newly identified studies, assessed study quality, and updated forest plots and meta-analyses. RESULTS: In addition to 31 previously included studies, five more were identified; three provided higher quality evidence. A randomised clinical trial (RCT) found no statistically significant differences in HIV risk among users of intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG implant) or the copper intrauterine device (Cu-IUD). An observational study found no statistically significant differences in HIV risk among women using DMPA, norethisterone enanthate (NET-EN), implants (type not specified) or Cu-IUD. Updated results from a previously included observational study continued to find a statistically significant increased HIV risk with oral contraceptives and DMPA compared with no contraceptive use, and found no association between LNG implant and HIV risk. CONCLUSIONS: High-quality RCT data comparing use of DMPA, LNG implant and Cu-IUD does not support previous concerns from observational studies that DMPA-IM use increases the risk of HIV acquisition. Use of other hormonal contraceptive methods (oral contraceptives, NET-EN and implants) is not associated with an increased risk of HIV acquisition.

2.
PLoS One ; 15(1): e0224359, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31914129

RESUMO

Sexually transmitted infections (STIs) and vaginal dysbiosis (disturbed resident microbiota presenting with abnormal Nugent score or candidiasis) have been associated with mucosal inflammation and risk of HIV-1 infection, cancer and poor reproductive outcomes. To date, the temporal relationships between aberrant cervical innate immunity and the clinical onset of microbial disturbance have not been studied in a large population of reproductive age women. We examined data from a longitudinal cohort of 934 Ugandan and Zimbabwean women contributing 3,274 HIV-negative visits who had complete laboratory, clinical and demographic data. Among those, 207 women later acquired HIV, and 584 women were intermittently diagnosed with C. trachomatis (CT), N. gonorrhoeae (NG), genital herpes (HSV-2), T. vaginalis (TV), candidiasis, and abnormal intermediate (4-6) or high (7-10) Nugent score, i.e. bacterial vaginosis (BV). Immune biomarker concentrations in cervical swabs were analyzed by generalized linear and mixed effect models adjusting for site, age, hormonal contraceptive use (HC), pregnancy, breastfeeding, genital practices, unprotected sex and overlapping infections. High likelihood ratios (1.5-4.9) denoted the values of cervical immune biomarkers to predict onset of abnormal Nugent score and candidiasis at the next visits. When controlling for covariates, higher levels of ß-defensin-2 were antecedent to BV, CT and HSV-2, lower anti-inflammatory ratio IL-1RA:IL-1ß-to intermediate Nugent scores and candida, lower levels of the serine protease inhibitor SLPI-to candida, lower levels of the adhesion molecule ICAM-1 -to TV, and lower levels of the oxidative stress mitigator and endothelial activation marker VEGF-to NG. Changes in innate immunity following onset of dysbiosis and infections were dependent on HC use when controlling for all other covariates. In conclusion, imminent female genital tract dysbiosis or infection can be predicted by distinct patterns of innate immunity. Future research should characterize biotic and abiotic determinants of this pre-existing innate immunity state.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31985699

RESUMO

BACKGROUND: We previously reported association of increased cervical RANTES and decreased SLPI with higher risk of HIV acquisition in reproductive age women. We now examine the interaction of concomitantly altered systemic and cervical immunity on such risk. METHODS: We measured immune biomarkers in 4390 cervical and 2390 paired serum specimens at quarterly visits in 218 HIV seroconverters and 784 seronegative women. We assessed proinflammatory (IL-1ß, IL-6, IL-8, MIP-3α, RANTES), anti-inflammatory (IL-1RA, SLPI), vascular activation (VEGF and ICAM-1) and defensin (BD2) cervical biomarkers and systemic (peripheral blood) CRP, IL-6, IL-7 and sCD14 as indicators of immune dysregulation. Biomarker levels were Box-Cox transformed and odds ratios for HIV acquisition calculated based on top quartile or higher/lower than median levels for all HIV negative visits. RESULTS: Subsequent HIV acquisition was associated with 5 of 14 individual biomarkers: low systemic CRP (OR=1.49, 1.21-1.83) and IL-6 (OR=1.23, 1.00-1.51), high cervical BD-2 (OR=1.33, 1.11-1.58) and RANTES (OR=1.20, 1.01-1.43) and low cervical IL-1RA (OR=0.65, 0.48-0.86). Low systemic CRP concomitant with altered cervical immunity, especially high BD2 conveyed highest HIV risk (1.63, 12.9-2.05). Additional markers of increased risk emerged when low systemic CRP coincided with: low systemic IL-6 and IL-7 (OR=1.53, 1.18-1.97); high cervical IL-8 and MIP-3α (OR=1.40, 1.07-1.83); high cervical IL-1ß and IL-6 (OR=1.43, 1.09-1.86); or low cervical SLPI (OR=1.36, 1.08-1.71). CONCLUSIONS: Changes in both peripheral and mucosal immunity may precede and predispose women to HIV infection. Suppressed systemic immunity (i.e. low CRP) alone or in combination with imbalanced cervical innate immunity (high proinflammatory and low anti-inflammatory mediators) indicated increased vulnerability to infection. Understanding these combined effects on HIV susceptibility is essential to preventing new infections.

4.
BMJ Sex Reprod Health ; 46(1): 17-25, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31919240

RESUMO

OBJECTIVES: To review systematically copper intrauterine device (Cu-IUD) use and HIV acquisition in women. METHODS: We searched Pubmed, Embase and the Cochrane Library between database inception and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using an unspecified IUD or Cu-IUD compared with non-hormonal or no contraceptive users, or hormonal contraceptive users. We extracted information from included studies, assessed study quality, and summarised study findings. RESULTS: From 2494 publications identified, seven met our inclusion criteria. One randomised controlled trial (RCT), judged "informative with few limitations", found no statistically significant differences in HIV risk between users of the Cu-IUD and either intramuscular depot medroxyprogesterone acetate (DMPA-IM) or levonorgestrel implant. One observational study, deemed "informative but with important limitations", found no statistically significant difference in HIV incidence among IUD users compared with women who had tubal ligation or who were not using any contraception. Another "informative but with important limitations" observational study found no difference in HIV incidence between Cu-IUD users and DMPA or norethisterone enanthate injectable, or implant users. An RCT considered "unlikely to inform the primary question" also found no difference in HIV risk between Cu-IUD and progestogen-only injectable users. Findings from the other three "unlikely to inform the primary question" cohort studies were consistent with the more robust studies suggesting no increased risk of HIV acquisition among Cu-IUD users. CONCLUSION: The collective evidence, including that from a large high-quality RCT, does not indicate an increased risk of HIV acquisition among users of Cu-IUDs.

5.
N Engl J Med ; 381(14): 1333-1346, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31577875

RESUMO

BACKGROUND: The safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown. METHODS: In this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years. RESULTS: A total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], -4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, -0.39; 95% CI, -1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 person-years in the deferred group (rate difference, 0.01; 95% CI, -0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9). CONCLUSIONS: The risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. (Funded by the National Institutes of Health; IMPAACT P1078 TB APPRISE ClinicalTrials.gov number, NCT01494038.).


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Isoniazida/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Tuberculose/prevenção & controle , Adolescente , Adulto , Antituberculosos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Isoniazida/efeitos adversos , Testes de Função Hepática , Período Pós-Parto , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Adulto Jovem
6.
J Acquir Immune Defic Syndr ; 81(5): 521-532, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31295174

RESUMO

BACKGROUND: In the multicountry PROMISE 1077BF/1077FF trial, the risk of low birth weight (LBW; <2500 g) and preterm delivery (PTD; <37 weeks) was significantly higher among women initiating a protease inhibitor-based antiretroviral treatment (ART) regimen than those receiving ZDV alone. Among those assigned to a protease inhibitor regimen, tenofovir/emtricitabine was associated with the more severe outcomes of very LBW (<1500 g) and very PTD (<34 weeks) compared with zidovudine/lamivudine. METHODS: We used multivariate logistic regression to further explore these treatment findings, taking into account demographic baseline clinical and postentry obstetrical factors. We evaluated individual adverse outcomes and composites that included stillbirth and early loss/spontaneous abortion. RESULTS: Among 3333 women delivering at least 1 live infant, median maternal age at enrollment was 26 years; 661 (20%) were primiparous, and 110 (3.3%) reported at least 1 previous PTD. Seventeen percent of newborns were LBW, 1% were very LBW, 17% had PTD, and 3% had very PTD. Treatment allocation remained strongly associated with multiple adverse outcomes after controlling for other risk factors with both ART regimens exhibiting increased risk relative to ZDV alone. Other risk factors remaining significant in at least one of the multivariate models included the following: country, gestational age at entry, maternal age, maternal body mass index, previous PTD, history of alcohol use, baseline HIV viral titer, multiple gestation, and several obstetric risk factors. CONCLUSIONS: ART effects on adverse pregnancy outcomes reported in the randomized PROMISE trial remained strongly significant even after controlling for demographic, baseline clinical, and obstetrical risk factors, which were also associated with these outcomes.

8.
Pan Afr Med J ; 34: 94, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31934237

RESUMO

Introduction: Abortion in Zimbabwe is allowed to preserve the physical health of the woman, or in cases of rape, incest, or fetal impairment. Access even under these conditions is difficult and rare. We aimed to understand knowledge of the abortion law and attitudes towards abortion amongst health care providers' and abortion experts in Zimbabwe as these can hinder access to safe legal abortion. Methods: In 2016, we conducted a Health Facility Survey (HFS) (n=227) among health care providers' knowledgeable about abortion services in their facility in a census of facilities offering Post Abortion Care (PAC), and a Health Professionals Survey (HPS) among 118 abortion experts. Results: Twenty-five percent of providers and 47% of experts knew all four reasons under which abortion is legal in Zimbabwe. Amongst providers and experts, 31% and 50% respectively were misinformed about one or more legal criteria. Most providers and experts were in support of expanding the legal provision of abortion to cases when the woman's mental health is at risk (65% and 79%, respectively) and if the woman is mentally incapacitated (66% amongst all). Seventy-one percent of experts recommend liberalizing the abortion law in order to reduce unsafe abortions. Conclusion: There is incomplete and sometimes inaccurate knowledge on the legal provisions for performing abortions in Zimbabwe amongst both health care providers and abortion experts. Incomplete knowledge of the law may be further reducing abortion access, highlighting the urgent need for educating health care providers on the legal status of abortion.


Assuntos
Aborto Induzido/psicologia , Aborto Legal/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/estatística & dados numéricos , Adulto , Atitude do Pessoal de Saúde , Estudos Transversais , Feminino , Pesquisas sobre Serviços de Saúde , Pessoal de Saúde/psicologia , Acesso aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Adulto Jovem , Zimbábue
9.
PLoS One ; 13(12): e0208805, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30543692

RESUMO

BACKGROUND: The PROMOTE study aims to measure long-term antiretroviral treatment (ART) safety and adherence; compare HIV disease progression; assess subsequent adverse pregnancy outcomes; evaluate effect of ART exposure on growth and development in HIV-exposed uninfected children; and assess long-term survival of mothers and children. This report primarily describes cohort characteristics at baseline to better understand long-term outcomes. METHODS AND FINDINGS: This is a prospective study. HIV-infected mothers and their children originally recruited in a multisite randomized clinical trial for prevention of perinatal HIV transmission were re-enrolled in PROMOTE. A total of 1987 mothers and 1784 children were enrolled from eight sites in Uganda, Malawi, Zimbabwe and South Africa. Most women (≥75%) reported being married in Malawi and Zimbabwe compared to low proportions in South Africa (4.4% in Durban and 15% in Soweto), and 43.5% in Uganda (p<0.001). There were variabilities in contraceptive practices: injectable contraceptive was the commonest reported method (40.9% overall); implant was the second commonest (15.7% overall); oral contraceptives were common in Zimbabwe; and tubal ligation was common in Malawi and South Africa. At baseline, 97.8% of women reported currently using ART; 96.4% were in WHO clinical class 1 or 2; median CD4 cell count was 825 cells per uL; and viral load was undetectable in 1637 (~85%) of the women. Approximately, 14% of women did not inform their primary partners of their own HIV status, 18% reported that they knew their partners were not HIV tested, and 9% did not know if partner was tested. Overall mean age of children at enrollment was 3.5 years; and 5.7% and 25.0% had weight-for-age and height-for-age z-scores <2 standard deviations, respectively. CONCLUSIONS: These baseline data show high adherence to ART use. However, issues of HIV disclosure and reproductive intentions remain important. In addition to ART and ensuring high adherence, other preventive measures should be included.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/transmissão , Transmissão Vertical de Doença Infecciosa/prevenção & controle , África ao Sul do Saara , Pré-Escolar , Progressão da Doença , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Humanos , Masculino , Adesão à Medicação , Gravidez , Estudos Prospectivos , Parceiros Sexuais , Resultado do Tratamento
10.
Syst Rev ; 7(1): 198, 2018 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-30447695

RESUMO

BACKGROUND: There is scanty or inconclusive evidence on which cervical cancer screening tool is effective and suitable for human immunodeficiency virus (HIV)-seropositive women. The aim of this review was to assess, synthesise and document published evidence relating to the available cervical cancer screening modalities for HIV-seropositive women in developing countries. This paper did not review the issue of human papillomavirus (HPV) prophylactic vaccine on HIV-seropositive women. METHODS: Five electronic databases were systematically searched from inception to January 2018 for relevant published original research examining cervical cancer prevention modalities for HPV infection, abnormal cytology and direct visualisation of the cervix amongst HIV-seropositive women in developing countries. Extra studies were identified through reference list and citation tracking. RESULTS: Due to methodological and clinical heterogeneity, a narrative synthesis was presented. Of the 2559 articles, 149 underwent full-text screening and 25 were included in the review. Included studies were of moderate quality, and no exclusions were made based on quality or bias. There is no standard cervical cancer screening test or programme for HIV-seropositive women and countries screening according to available resources and expertise. The screening methods used for HIV-seropositive women are the same for HIV-negative women, with varying clinical performance and accuracy. The main cervical cancer screening methods described for HIV-seropositive women are HPV deoxyribonucleic acid/messenger RNA (DNA/mRNA) testing (n = 16, 64.0%), visual inspection with acetic acid (VIA) (n = 13, 52.0%) and Pap smear (n = 11, 44.0%). HPV testing has a better accuracy/efficiency than other methods with a sensitivity of 80.0-97.0% and specificity of 51.0-78.0%. Sequential screening using VIA or visual inspection with Lugol's iodine (VILI) and HPV testing has shown better clinical performance in screening HIV-seropositive women. CONCLUSION: Although cervical cancer screening exists in almost all developing countries, what is missing is both opportunistic and systematic organised population-based screenings. Cervical cancer screening programmes need to be integrated into already existing HIV services to enable early detection and treatment. There is a need to offer opportunistic and coordinated screening programmes that are provider-initiated to promote early identification of cervical precancerous lesions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018095702.


Assuntos
Detecção Precoce de Câncer/métodos , Infecções por Papillomavirus/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Países em Desenvolvimento , Feminino , Soropositividade para HIV , Testes de DNA para Papilomavírus Humano , Humanos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Esfregaço Vaginal
11.
PLoS One ; 13(10): e0205239, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30356264

RESUMO

BACKGROUND: Zimbabwe has the highest contraceptive prevalence rate in sub-Saharan Africa, but also one of the highest maternal mortality ratios in the world. Little is known, however, about the incidence of abortion and post-abortion care (PAC) in Zimbabwe. Access to legal abortion is rare, and limited to circumstances of rape, incest, fetal impairment, or to save the woman's life. OBJECTIVES: This paper estimates a) the national provision of PAC, b) the first-ever national incidence of induced abortion in Zimbabwe, and c) the proportion of pregnancies that are unintended. METHODS: We use the Abortion Incidence Complications Method (AICM), which indirectly estimates the incidence of induced abortion by obtaining a national estimate of PAC cases, and then estimates what proportion of all induced abortions in the country would result in women receiving PAC. Three national surveys were conducted in 2016: a census of health facilities with PAC capacity (n = 227), a prospective survey of women seeking abortion-related care in a nationally-representative sample of those facilities (n = 127 facilities), and a purposive sample of experts knowledgeable about abortion in Zimbabwe (n = 118). The estimate of induced abortion, along with census and Demographic Health Survey data was used to estimate unintended pregnancy. RESULTS: There were an estimated 25,245 PAC patients treated in Zimbabwe in 2016, but there were critical gaps in their care, including stock-outs of essential PAC medicines at half of facilities. Approximately 66,847 induced abortions (uncertainty interval (UI): 54,000-86,171) occurred in Zimbabwe in 2016, which translates to a national rate of 17.8 (UI: 14.4-22.9) abortions per 1,000 women 15-49. Overall, 40% of pregnancies were unintended in 2016, and one-quarter of all unintended pregnancies ended in abortion. CONCLUSION: Zimbabwe has one of the lowest abortion rates in sub-Saharan Africa, likely due to high rates of contraceptive use. There are gaps in the health care system affecting the provision of quality PAC, potentially due to the prolonged economic crisis. These findings can inform and improve policies and programs addressing unsafe abortion and PAC in Zimbabwe.


Assuntos
Aborto Induzido , Aborto Espontâneo/epidemiologia , Gravidez não Planejada , Aborto Legal , Aborto Espontâneo/mortalidade , Aborto Espontâneo/fisiopatologia , Adolescente , Adulto , Censos , Feminino , Inquéritos Epidemiológicos , Humanos , Mortalidade Materna , Gravidez , Estudos Prospectivos , Zimbábue/epidemiologia
12.
AIDS Res Hum Retroviruses ; 34(10): 889-899, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30047279

RESUMO

Hormonal contraception (HC), particularly injectable depot-medroxyprogesterone acetate (DMPA), has been associated with increased HIV acquisition and higher levels of cervical regulated upon activation, normal T-cell expressed, and secreted (RANTES), also associated with HIV seroconversion. Longitudinal changes in cervical immunity associated with DMPA and combined oral contraceptives (COCs) have not been studied. Cervical samples from 216 HIV seroconverters in Uganda and Zimbabwe with matched samples from 727 HIV-uninfected controls were collected at two quarterly visits before (t - 2, t - 1), at (t0), and two visits following (t + 1, t + 2) HIV seroconversion and corresponding visits for HIV-negative controls. We measured 10 biomarkers of inflammation and immunity and used generalized linear models to estimate and compare biomarker levels across HIV status, contraceptive, and pregnancy groups. Biomarkers remained relatively stable across visits for controls, while in HIV-infected women cervical immunity started to change before seroconversion with RANTES and BD-2 increased and secretory leukocyte protease inhibitor (SLPI) decreased at t - 1 and continued to change at t0 with ICAM-1 up and IL-8 down and with more biomarkers after seroconversion (IL-1ß, IL-6, MIP-3α, VEGF, and IL-1RA down and IL-1RA:IL-1ß ratio up). In multivariable analyses, seroconverters had higher BD-2 at t - 1, higher RANTES and lower SLPI from t - 1 through t + 2, and lower IL-8 and IL-1RA at and/or after seroconversion compared to nonseroconverters. Compared to non-HC users, DMPA users had higher RANTES at all visits and lower BD-2 at t - 2 through t0, while COC users and pregnant women had higher IL-8 and SLPI at all visits; COC users also had lower BD-2 preseroconversion; pregnant women had lower RANTES at t0 - t + 2. Longitudinal patterns of cervical immunity differ between HIV seroconverters and HIV-negative women; seroconverters demonstrate increased RANTES and decreased SLPI starting before and continuing postseroconversion. Furthermore, these patterns are differentially regulated by DMPA, COC, and pregnancy.


Assuntos
Colo do Útero/imunologia , Anticoncepcionais Orais Hormonais/imunologia , Infecções por HIV/imunologia , Mediadores da Inflamação/metabolismo , Adolescente , Adulto , Biomarcadores/metabolismo , Colo do Útero/metabolismo , Anticoncepcionais Orais Combinados/imunologia , Anticoncepcionais Orais Hormonais/administração & dosagem , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/metabolismo , Humanos , Estudos Longitudinais , Acetato de Medroxiprogesterona/imunologia , Gravidez , Soroconversão , Uganda/epidemiologia , Esfregaço Vaginal , Adulto Jovem , Zimbábue/epidemiologia
13.
BMJ Open ; 8(2): e019658, 2018 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-29440163

RESUMO

OBJECTIVES: Abortion complications cause significant morbidity and mortality. We aimed to assess the severity and factors associated with abortion complications (induced or spontaneous), and the management of postabortion care (PAC) in Zimbabwe. DESIGN: Prospective, facility-based 28 day survey among women seeking PAC and their providers. SETTING: 127 facilities in Zimbabwe with the capacity to provide PAC, including all central and provincial hospitals, and a sample of primary health centres (30%), district/general/mission hospitals (52%), private (77%) and non-governmental organisation (NGO) (68%) facilities. PARTICIPANTS: 1002 women presenting with abortion complications during the study period. MAIN OUTCOME MEASURES: Severity of abortion complications and associated factors, delays in care seeking, and clinical management of complications. RESULTS: Overall, 59% of women had complications classified as mild, 19% as moderate, 19% as severe, 3% as near miss and 0.2% died. A median of 47 hours elapsed between experiencing complication and receiving treatment; many delays were due to a lack of finances. Women who were rural, younger, not in union, less educated, at later gestational ages or who had more children were significantly more likely to have higher severity complications. Most women were treated by doctors (91%). The main management procedure used was dilatation and curettage/dilatation and evacuation (75%), while 12% had manual vacuum aspiration (MVA) or electrical vacuum aspiration and 11% were managed with misoprostol. At discharge, providers reported that 43% of women received modern contraception. CONCLUSION: Zimbabwean women experience considerable abortion-related morbidity, particularly young, rural or less educated women. Abortion-related morbidity and concomitant mortality could be reduced in Zimbabwe by liberalising the abortion law, providing PAC in primary health centres, and training nurses to use medical evacuation with misoprostol and MVA. Regular in-service training on PAC guidelines with follow-up audits are needed to ensure compliance and availability of equipment, supplies and trained staff.


Assuntos
Aborto Induzido/efeitos adversos , Aborto Espontâneo/epidemiologia , Anticoncepção/estatística & dados numéricos , Complicações Pós-Operatórias/mortalidade , Curetagem a Vácuo/efeitos adversos , Abortivos não Esteroides/uso terapêutico , Adolescente , Adulto , Assistência ao Convalescente/métodos , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Misoprostol/uso terapêutico , Análise Multivariada , Complicações Pós-Operatórias/terapia , Gravidez , Estudos Prospectivos , Análise de Regressão , Índice de Gravidade de Doença , Adulto Jovem , Zimbábue/epidemiologia
14.
PLoS Pathog ; 14(1): e1006754, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29346424

RESUMO

In the majority of cases, human immunodeficiency virus type 1 (HIV-1) infection is transmitted through sexual intercourse. A single founder virus in the blood of the newly infected donor emerges from a genetic bottleneck, while in rarer instances multiple viruses are responsible for systemic infection. We sought to characterize the sequence diversity at early infection, between two distinct anatomical sites; the female reproductive tract vs. systemic compartment. We recruited 72 women from Uganda and Zimbabwe within seven months of HIV-1 infection. Using next generation deep sequencing, we analyzed the total genetic diversity within the C2-V3-C3 envelope region of HIV-1 isolated from the female genital tract at early infection and compared this to the diversity of HIV-1 in plasma. We then compared intra-patient viral diversity in matched cervical and blood samples with three or seven months post infection. Genetic analysis of the C2-V3-C3 region of HIV-1 env revealed that early HIV-1 isolates within blood displayed a more homogeneous genotype (mean 1.67 clones, range 1-5 clones) than clones in the female genital tract (mean 5.7 clones, range 3-10 clones) (p<0.0001). The higher env diversity observed within the genital tract compared to plasma was independent of HIV-1 subtype (A, C and D). Our analysis of early mucosal infections in women revealed high HIV-1 diversity in the vaginal tract but few transmitted clones in the blood. These novel in vivo finding suggest a possible mucosal sieve effect, leading to the establishment of a homogenous systemic infection.


Assuntos
Colo do Útero/virologia , Variação Genética , Infecções por HIV/virologia , Soropositividade para HIV/virologia , HIV-1/genética , Vagina/virologia , Viremia/virologia , Sequência de Bases , Estudos de Coortes , Feminino , Soropositividade para HIV/sangue , HIV-1/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estudos Longitudinais , RNA Viral/sangue , RNA Viral/química , RNA Viral/isolamento & purificação , Infecções do Sistema Genital/sangue , Infecções do Sistema Genital/virologia , Uganda , Carga Viral , Viremia/sangue , Zimbábue , Produtos do Gene env do Vírus da Imunodeficiência Humana/química , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
15.
Syst Rev ; 7(1): 22, 2018 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-29370853

RESUMO

BACKGROUND: Cervical cancer has become the most common cancer affecting women in Africa. Significantly, 85% of these annual deaths occur in the developing world, with the majority being middle-aged women. Research has shown that in sub-Saharan Africa, cervical cancer trends are on the rise in the past two decades because of HIV and this has resulted in an increase in cervical cancer cases among young women. However, little or no information exists that has shown that any of the available treatment methods are more effective than others when it comes to treating cervical cancer in HIV-seropositive women. The aim of this protocol is to offer a plan on how to systematically review cervical cancer treatment methods available for HIV-seropositive women in developing countries. METHODS/DESIGN: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement was used to develop the protocol for the systematic review which will be reported in accordance with the PRISMA guidelines. A number of databases, Embase, MEDLINE, PubMed, CINAHL and Cochrane Library, will be searched for relevant studies, and citation and reference list tracking will be used to search for additional studies. Prospective and retrospective cohort studies, case-control, randomised controlled trials and cross-sectional studies that were carried out in and for the developing world will be eligible for inclusion. Peer-reviewed studies and grey literature examining cervical cancer treatment modalities in HIV-seropositive women will be included. Descriptive statistics and tables will be used to summarise results, and meta-analysis will be used where appropriate. DISCUSSION: The review findings will provide the current picture of the existing treatment methods being used to treat cervical cancer in HIV-seropositive women in developing countries. The findings might be used for the establishment of evidence-based guidelines for treatment of cervical cancer in seropositive women as well as prompt policy-makers and governments to decide and support future research in a way to find a lasting solution. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017054676 https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=54676.


Assuntos
Soropositividade para HIV/complicações , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/terapia , África , Países em Desenvolvimento , Feminino , Humanos
16.
HIV Clin Trials ; 19(6): 209-224, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30890061

RESUMO

BACKGROUND: IMPAACT PROMISE 1077BF/FF was a randomized study of antiretroviral therapy (ART) strategies for pregnant and postpartum women with high CD4+ T-cell counts. We describe postpartum outcomes for women in the study who were randomized to continue or discontinue ART after delivery. METHODS: Women with pre-ART CD4+ cell counts ≥350 cells/mm3 who started ART during pregnancy were randomized postpartum to continue or discontinue treatment. Women were enrolled from India, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. The primary outcome was a composite of progression to AIDS-defining illness or death. Log-rank tests and Cox regression models assessed treatment effects. Incidence rates were calculated per 100 person-years. A post hoc analysis evaluated WHO Stage 2/3 events. All analyses were intent-to-treat. FINDINGS: 1611 women were enrolled (June 2011-October 2014) and 95% were breastfeeding. Median age at entry was 27 years, CD4+ count 728 cells/mm3 and the majority of women were Black African (97%). After a median follow-up of 1.6 years, progression to AIDS-defining illness or death was rare and there was no significant difference between arms (HR: 0·55; 95%CI 0·14, 2·08, p = 0.37). WHO Stage 2/3 events were reduced with continued ART (HR: 0·60; 95%CI 0·39, 0·90, p = 0.01). The arms did not differ with respect to the rate of grade 2, 3, or 4 safety events (p = 0.61). INTERPRETATION: Serious clinical events were rare among predominately breastfeeding women with high CD4+ cell counts over 18 months after delivery. ART had significant benefit in reducing WHO 2/3 events in this population.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Saúde Materna , Adulto , Aleitamento Materno , Contagem de Linfócito CD4 , Progressão da Doença , Feminino , Infecções por HIV/virologia , Humanos , Período Pós-Parto , Gravidez , Resultado do Tratamento , Adulto Jovem
17.
Syst Rev ; 6(1): 91, 2017 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-28438187

RESUMO

BACKGROUND: Over 85% of cervical cancer cases and deaths occur in developing countries. HIV-seropositive women are more likely to develop precancerous lesions that lead to cervical cancer than HIV-negative women. However, the literature on cervical cancer prevention in seropositive women in developing countries has not been reviewed. The aim of this study is to systematically review cervical cancer prevention modalities available for HIV-seropositive women in developing countries. METHODS/DESIGN: This protocol was developed by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement, and the systematic review will be reported in accordance with the PRISMA guidelines. Embase, MEDLINE, PubMed, CINAHL and Cochrane Library will be searched from inception up to date of final search, and additional studies will be located through citation and reference list tracking. Eligible studies will be randomised controlled trials, prospective and retrospective cohort studies, case-control and cross-sectional studies carried out in developing countries. Studies will be included if they are published in English and examine cervical cancer prevention modalities in HIV-seropositive women. Results will be summarised in tables and, where appropriate, combined using meta-analysis. DISCUSSION: This review will address the gap in evidence by systematically reviewing the published literature on the different prevention modalities being used to prevent cervical cancer in HIV-seropositive women in developing countries. The findings may be used to inform evidence-based guidelines for prevention of cervical cancer in seropositive women as well as future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017054678 .


Assuntos
Países em Desenvolvimento , Soropositividade para HIV/complicações , Projetos de Pesquisa , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/prevenção & controle , Feminino , Humanos , Revisão Sistemática como Assunto
18.
AIDS Res Hum Retroviruses ; 33(6): 555-557, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28318310

RESUMO

Accurate methods for cross-sectional incidence estimation are needed for HIV prevention research. The Limiting Antigen Avidity (LAg-Avidity) assay has been marketed by two vendors, Maxim Biomedical and Sedia BioSciences Corporation. Performance differences between the two versions of the assay are unknown. We tested a total 1,410 treatment-naive samples with both versions of the assay. The samples came from 176 seroconverters from the Zimbabwe Hormonal Contraception and HIV Study. The correlation between the two versions of the assay was 0.93 for the optical density (OD) and 0.86 for the normalized OD. As the difference was more pronounced for the normalized OD, the difference in assays can be attributed to the calibrators. The mean duration of recent infection (MDRI), the average time individuals infected <2 years appear recently infected, was determined for both versions using an assay cutoff of 1.5 OD-n alone or in combination with a viral load cutoff of >1,000 copies/ml. The MDRI was 137 days for Sedia and 157 days for Maxim, with a difference of 20 days (95% CI 11-30). The MDRIs decreased to 102 and 120 days with the inclusion of a viral load cutoff of >1,000 copies/ml. These results imply that use of the Sedia LAg-Avidity will result in estimates of incidence ∼13% lower than those using the Maxim LAg-Avidity.


Assuntos
Métodos Epidemiológicos , Antígenos HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Testes Sorológicos/métodos , Estudos Transversais , Humanos , Incidência , Zimbábue/epidemiologia
19.
Gates Open Res ; 1: 17, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29355224

RESUMO

Background: In vitro, animal, biological and observational clinical studies suggest that some hormonal methods, particularly depot medroxyprogesterone acetate - DMPA, may increase women's risk of HIV acquisition. DMPA is the most common contraceptive used in many countries worst affected by the HIV epidemic. To provide robust evidence for contraceptive decision-making among women, clinicians and planners, we are conducting the Evidence for Contraceptive Options and HIV Outcomes (ECHO) study in four countries with high HIV incidence and DMPA use: Kenya, South Africa, Swaziland, and Zambia (Clinical Trials.gov identifier NCT02550067). Study design: We randomized HIV negative, sexually active women 16-35 years old requesting effective contraception and agreeing to participate to either DMPA, the copper T 380A intrauterine device or levonorgestrel implant. Participants attend a contraception support visit after 1 month and quarterly visits thereafter for up to 18 months. Participants receive a standard HIV prevention package and contraceptive side-effect management at each visit. The primary outcome is HIV seroconversion. Secondary outcomes include pregnancy, serious adverse events and method discontinuation. The sample size of 7800 women provides 80% power to detect a 50% relative increase in HIV risk between any of the three method pairs, assuming 250 incident infections per comparison. Ethical considerations: Several WHO consultations have concluded that current evidence on HIV risk associated with DMPA is inconclusive and that a randomized trial is needed to guide policy, counselling and choice. Previous studies suggest that women without a specific contraceptive preference are willing to accept randomization to different contraceptive methods. Stringent performance standards are monitored by an independent data and safety monitoring board approximately every 6 months. The study has been conducted with extensive stakeholder engagement. Conclusions: The ECHO study is designed to provide robust evidence on the relative risks (HIV acquisition) and benefits (pregnancy prevention) between three effective contraceptive methods.

20.
N Engl J Med ; 375(18): 1726-1737, 2016 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-27806243

RESUMO

BACKGROUND: Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. METHODS: We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety. RESULTS: The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, -1.3 percentage points; repeated confidence interval, -2.1 to -0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated with higher rates than zidovudine-based ART of very preterm delivery before 34 weeks (6.0% vs. 2.6%, P=0.04) and early infant death (4.4% vs. 0.6%, P=0.001), but there were no significant differences between tenofovir-based ART and zidovudine alone (P=0.10 and P=0.43). The rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART. CONCLUSIONS: Antenatal ART resulted in significantly lower rates of early HIV transmission than zidovudine alone but a higher risk of adverse maternal and neonatal outcomes. (Funded by the National Institutes of Health; PROMISE ClinicalTrials.gov numbers, NCT01061151 and NCT01253538 .).


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/prevenção & controle , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Zidovudina/uso terapêutico , Adulto , Afro-Americanos , Antirretrovirais/efeitos adversos , Contagem de Linfócito CD4 , Quimioterapia Combinada , Feminino , Idade Gestacional , Infecções por HIV/etnologia , Infecções por HIV/transmissão , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Nevirapina/administração & dosagem , Assistência Perinatal , Gravidez , Resultado da Gravidez , Tenofovir/uso terapêutico , Adulto Jovem , Zidovudina/efeitos adversos
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