Journal Article > ResearchFull Text
Lancet Infect Dis. 2013 April 1; Volume 13 (Issue 4); 303-312.; DOI:10.1016/S1473-3099(13)70007-0
Bonnet MMB, Bhatt NB, Baudin E, Silva C, Michon C, et al.
Lancet Infect Dis. 2013 April 1; Volume 13 (Issue 4); 303-312.; DOI:10.1016/S1473-3099(13)70007-0
BACKGROUND
In countries with a high incidence of HIV and tuberculosis co-infection, nevirapine and efavirenz are widely used as antiretroviral therapy but both interact with antituberculosis drugs. We aimed to compare efficacy and safety of a nevirapine-based antiretroviral therapy (started at full dose) with an efavirenz-based regimen in co-infected patients.
METHODS
We did a multicentre, open-label, randomised, non-inferiority trial at three health centres in Maputo, Mozambique. We enrolled adults (≥18 years) with tuberculosis and previously untreated HIV infection (CD4 cell counts <250 cells per μL) and alanine aminotransferase and total bilirubin concentrations of less than five times the upper limit of normal. 4-6 weeks after the start of tuberculosis treatment, we randomly allocated patients (1:1) with central randomisation, block sizes of two to six, and stratified by site and CD4 cell count to nevirapine (200 mg twice daily) or efavirenz (600 mg once daily), plus lamivudine and stavudine. The primary endpoint was virological suppression at 48 weeks (HIV-1 RNA <50 copies per mL) in all patients who received at least one dose of study drug (intention-to-treat population); death and loss to follow-up were recorded as treatment failure. The non-inferiority margin for the difference of efficacy was 10%. We assessed efficacy in intention-to-treat and per-protocol populations and safety in all patients who received study drug. This study is registered with ClinicalTrials.gov, number NCT00495326.
FINDINGS
Between October, 2007, and March, 2010, we enrolled 285 patients into each group. 242 (85%) patients in the nevirapine group and 233 (82%) patients in the efavirenz group completed follow-up. In the intention-to-treat population, 184 patients (64·6%, 95% CI 58·7-70·1) allocated nevirapine achieved virological suppression at week 48, as did 199 patients (69·8%, 64·1-75·1) allocated efavirenz (one-sided 95% CI of the difference of efficacy 11·7%). In the per-protocol population, 170 (70·0%, 63·8-75·7) of 243 patients allocated nevirapine achieved virological suppression at week 48, as did 194 (78·9%, 73·2-83·8) of 246 patients allocated efavirenz (one-sided 95% CI 15·4%). The median CD4 cell count at randomisation was 89 cells per μL. 15 patients substituted nevirapine with efavirenz and six patients substituted efavirenz with nevirapine. 20 patients allocated nevirapine (7%) had grade 3-4 increase of alanine aminotransferase compared with 17 patients allocated efavirenz (6%). Three patients had severe rash after receipt of nevirapine (1%) but no patients did after receipt of efavirenz. 18 patients in the nevirapine group died, as did 17 patients in the efavirenz group.
INTERPRETATION
Although non-inferiority of the nevirapine-regimen was not shown, nevirapine at full dose could be a safe, acceptable alternative for patients unable to tolerate efavirenz. FUNDING: French Research Agency for HIV/AIDS and hepatitis (ANRS).
In countries with a high incidence of HIV and tuberculosis co-infection, nevirapine and efavirenz are widely used as antiretroviral therapy but both interact with antituberculosis drugs. We aimed to compare efficacy and safety of a nevirapine-based antiretroviral therapy (started at full dose) with an efavirenz-based regimen in co-infected patients.
METHODS
We did a multicentre, open-label, randomised, non-inferiority trial at three health centres in Maputo, Mozambique. We enrolled adults (≥18 years) with tuberculosis and previously untreated HIV infection (CD4 cell counts <250 cells per μL) and alanine aminotransferase and total bilirubin concentrations of less than five times the upper limit of normal. 4-6 weeks after the start of tuberculosis treatment, we randomly allocated patients (1:1) with central randomisation, block sizes of two to six, and stratified by site and CD4 cell count to nevirapine (200 mg twice daily) or efavirenz (600 mg once daily), plus lamivudine and stavudine. The primary endpoint was virological suppression at 48 weeks (HIV-1 RNA <50 copies per mL) in all patients who received at least one dose of study drug (intention-to-treat population); death and loss to follow-up were recorded as treatment failure. The non-inferiority margin for the difference of efficacy was 10%. We assessed efficacy in intention-to-treat and per-protocol populations and safety in all patients who received study drug. This study is registered with ClinicalTrials.gov, number NCT00495326.
FINDINGS
Between October, 2007, and March, 2010, we enrolled 285 patients into each group. 242 (85%) patients in the nevirapine group and 233 (82%) patients in the efavirenz group completed follow-up. In the intention-to-treat population, 184 patients (64·6%, 95% CI 58·7-70·1) allocated nevirapine achieved virological suppression at week 48, as did 199 patients (69·8%, 64·1-75·1) allocated efavirenz (one-sided 95% CI of the difference of efficacy 11·7%). In the per-protocol population, 170 (70·0%, 63·8-75·7) of 243 patients allocated nevirapine achieved virological suppression at week 48, as did 194 (78·9%, 73·2-83·8) of 246 patients allocated efavirenz (one-sided 95% CI 15·4%). The median CD4 cell count at randomisation was 89 cells per μL. 15 patients substituted nevirapine with efavirenz and six patients substituted efavirenz with nevirapine. 20 patients allocated nevirapine (7%) had grade 3-4 increase of alanine aminotransferase compared with 17 patients allocated efavirenz (6%). Three patients had severe rash after receipt of nevirapine (1%) but no patients did after receipt of efavirenz. 18 patients in the nevirapine group died, as did 17 patients in the efavirenz group.
INTERPRETATION
Although non-inferiority of the nevirapine-regimen was not shown, nevirapine at full dose could be a safe, acceptable alternative for patients unable to tolerate efavirenz. FUNDING: French Research Agency for HIV/AIDS and hepatitis (ANRS).
Technical Report > Evidence Brief
Pasquier E, Owolabi OO, Fetters T, Chen H, Williams TN, et al.
2022 August 30
English
Français
Abortion complications remain a major cause of maternal mortality worldwide and abortion-related mortality has decreased very little over the last decade, unlike maternal mortality linked to other main causes such as haemorrhage, infection or obstructed labour. Global estimates suggest that most abortion-related deaths are the result of unsafe induced abortions, 97% of which occur in low- and middle-income countries which can be largely prevented by providing comprehensive abortion care, including post- abortion care, contraceptive services, and safe abortion care.
At 829 deaths for every 100,000 live births, the Central African Republic (CAR) has one of the world’s highest maternal mortality ratios. Abortion-related complications are a major contributor to maternal mortality, estimated at almost one in four (24%) of the maternal deaths in one study led by the Central African Ministry of Health and UNFPA. Further, CAR is one of the most fragile countries in the world, rating 174th out of the 178 countries in the Fund for Peace Fragility Index with different parts of the country regularly affected by decades-long armed conflict.
A lack of evidence on abortion complications in fragile settings limits the understanding of women’s needs in access to comprehensive abortion care in this context. This study describes the burden of abortion-related complications and their contributing factors in the maternity of Castors in Bangui, CAR. This evidence brief presents selected results of two components of the AMoCo Study (Abortion-related Morbidity and Mortality in Conflict-affected and Fragile Settings): 1) A quantitative observational study of clinical characteristics of women presenting with any type of abortion complications, and 2) A quantitative survey with a sub-group of these women who were hospitalized.
At 829 deaths for every 100,000 live births, the Central African Republic (CAR) has one of the world’s highest maternal mortality ratios. Abortion-related complications are a major contributor to maternal mortality, estimated at almost one in four (24%) of the maternal deaths in one study led by the Central African Ministry of Health and UNFPA. Further, CAR is one of the most fragile countries in the world, rating 174th out of the 178 countries in the Fund for Peace Fragility Index with different parts of the country regularly affected by decades-long armed conflict.
A lack of evidence on abortion complications in fragile settings limits the understanding of women’s needs in access to comprehensive abortion care in this context. This study describes the burden of abortion-related complications and their contributing factors in the maternity of Castors in Bangui, CAR. This evidence brief presents selected results of two components of the AMoCo Study (Abortion-related Morbidity and Mortality in Conflict-affected and Fragile Settings): 1) A quantitative observational study of clinical characteristics of women presenting with any type of abortion complications, and 2) A quantitative survey with a sub-group of these women who were hospitalized.
Journal Article > ResearchFull Text
Malar J. 2013 July 17; Volume 12 (Issue 1); 250.; DOI:10.1186/1475-2875-12-250
Schramm B, Valeh P, Baudin E, Mazinda CS, Smith R, et al.
Malar J. 2013 July 17; Volume 12 (Issue 1); 250.; DOI:10.1186/1475-2875-12-250
BACKGROUND
Safety surveillance of widely used artemisinin-based combination therapy (ACT) is essential, but tolerability data in the over five years age group are largely anecdotal.
METHODS
Two open-label, randomized trials were conducted in Nimba County, Liberia: i) the main tolerability trial with 1,000 Plasmodium falciparum malaria patients aged over five years (Study-T), and, ii) an efficacy trial with a secondary objective of collecting tolerability data among 300 children age six to 59 months (Study-E). In both studies patients were randomized to fixed-dose artesunate-amodiaquine (ASAQ Winthrop®) or artemether-lumefantrine (AL, Coartem®), respectively. Clinical- and laboratory-adverse events (AEs) were recorded until day 28.
RESULTS
Study-T: most patients experienced at least one AE. Severe AEs were few, primarily asymptomatic blood system disorders or increased liver enzyme values. No treatment or study discontinuation occurred. Mild or moderate fatigue (39.8% vs 16.3%, p < 0.001), vomiting (7.1% vs 1.6%, p < 0.001), nausea (3.2% vs 1.0%, p = 0.01), and anaemia (14.9% vs 9.8%, p = 0.01) were more frequently recorded in the ASAQ versus AL arm. Study-E: mild or moderate AEs were common, including anaemia, fatigue, vomiting or diarrhoea. The few severe events were asymptomatic blood system disorders and four clinical events (pneumonia, malaria, vomiting and stomatitis).
CONCLUSION
Both ASAQ and AL were well tolerated in patients of all age groups. No unexpected AEs occurred. Certain mild or moderate AEs were more frequent in the ASAQ arm. Standardised safety surveillance should continue for all forms of ACT.
TRIAL REGISTRATION
The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN40020296, ISRCTN51688713, (http://www.controlled-trials.com).
Safety surveillance of widely used artemisinin-based combination therapy (ACT) is essential, but tolerability data in the over five years age group are largely anecdotal.
METHODS
Two open-label, randomized trials were conducted in Nimba County, Liberia: i) the main tolerability trial with 1,000 Plasmodium falciparum malaria patients aged over five years (Study-T), and, ii) an efficacy trial with a secondary objective of collecting tolerability data among 300 children age six to 59 months (Study-E). In both studies patients were randomized to fixed-dose artesunate-amodiaquine (ASAQ Winthrop®) or artemether-lumefantrine (AL, Coartem®), respectively. Clinical- and laboratory-adverse events (AEs) were recorded until day 28.
RESULTS
Study-T: most patients experienced at least one AE. Severe AEs were few, primarily asymptomatic blood system disorders or increased liver enzyme values. No treatment or study discontinuation occurred. Mild or moderate fatigue (39.8% vs 16.3%, p < 0.001), vomiting (7.1% vs 1.6%, p < 0.001), nausea (3.2% vs 1.0%, p = 0.01), and anaemia (14.9% vs 9.8%, p = 0.01) were more frequently recorded in the ASAQ versus AL arm. Study-E: mild or moderate AEs were common, including anaemia, fatigue, vomiting or diarrhoea. The few severe events were asymptomatic blood system disorders and four clinical events (pneumonia, malaria, vomiting and stomatitis).
CONCLUSION
Both ASAQ and AL were well tolerated in patients of all age groups. No unexpected AEs occurred. Certain mild or moderate AEs were more frequent in the ASAQ arm. Standardised safety surveillance should continue for all forms of ACT.
TRIAL REGISTRATION
The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN40020296, ISRCTN51688713, (http://www.controlled-trials.com).
Journal Article > Meta-AnalysisFull Text
BMC Med. 2020 February 25; Volume 18 (Issue 1); 47.; DOI:10.1186/s12916-020-1494-3.
Bretscher MT, Dahal P, Griffin J, Stepniewska K, Bassat Q, et al.
BMC Med. 2020 February 25; Volume 18 (Issue 1); 47.; DOI:10.1186/s12916-020-1494-3.
BACKGROUND
The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas.
METHODS
We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of post-treatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment.
RESULTS
We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7-15.7) for AL and 15.2 days (95% CI 12.8-18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7-18.6 days for AL and 10.2-18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated (<=20% 86Y and 76T mutants, respectively), AS-AQ provided ~ 2-fold longer protection than AL. Conversely, at a higher prevalence of 86Y and 76T mutant parasites (> 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter population-level clinical incidence of malaria by up to 14% in under-5-year-old children when the drugs were used as first-line treatments in areas with high, seasonal transmission.
CONCLUSION
Choosing a first-line treatment which provides optimal post-treatment prophylaxis given the local prevalence of resistance-associated markers could make a significant contribution to reducing malaria morbidity.
The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas.
METHODS
We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of post-treatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment.
RESULTS
We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7-15.7) for AL and 15.2 days (95% CI 12.8-18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7-18.6 days for AL and 10.2-18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated (<=20% 86Y and 76T mutants, respectively), AS-AQ provided ~ 2-fold longer protection than AL. Conversely, at a higher prevalence of 86Y and 76T mutant parasites (> 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter population-level clinical incidence of malaria by up to 14% in under-5-year-old children when the drugs were used as first-line treatments in areas with high, seasonal transmission.
CONCLUSION
Choosing a first-line treatment which provides optimal post-treatment prophylaxis given the local prevalence of resistance-associated markers could make a significant contribution to reducing malaria morbidity.
Protocol > Research Study
Pasquier E, Fetters T, Owolabi OO, Ngbale RN, Moore AM, et al.
2020 December 15
OVERALL AIM
To describe and estimate the burden of abortion-related complications, particularly near-miss complications and deaths, and their associated factors among women presenting for abortion-related complications in health facilities supported by Médecins Sans Frontières (MSF) in African fragile and/or conflict-affected settings.
OBJECTIVES
Primary objective:
- To describe the frequency of near-miss events and deaths among women presenting for
abortion-related complications.
Secondary objective:
- To describe the frequency of abortion-related complications overall and by types (hemorrhage, infection, perforation, etc.)
- To describe the severity of abortion-related complications overall and by types (hemorrhage, infection, perforation, etc.)
- To identify risk factors quantitatively associated with abortion-related near-miss events;
- To describe the quality of the clinical management of abortion-related complications
(including near-miss cases) and the heath facilities capacity to manage these complications
- To describe the experiences of women who present as near-miss cases, including their
decision-making processes, access, pathways to care as well as conditions and factors that
could contribute to the life-threatening conditions and near-miss event.
- To describe the knowledge, attitudes, practices, and behaviors of health care workers in
relation to abortion;
- To describe the characteristics, management, outcomes of ectopic and molar pregnancies
ClinicalTrials.gov: NCT04331847
To describe and estimate the burden of abortion-related complications, particularly near-miss complications and deaths, and their associated factors among women presenting for abortion-related complications in health facilities supported by Médecins Sans Frontières (MSF) in African fragile and/or conflict-affected settings.
OBJECTIVES
Primary objective:
- To describe the frequency of near-miss events and deaths among women presenting for
abortion-related complications.
Secondary objective:
- To describe the frequency of abortion-related complications overall and by types (hemorrhage, infection, perforation, etc.)
- To describe the severity of abortion-related complications overall and by types (hemorrhage, infection, perforation, etc.)
- To identify risk factors quantitatively associated with abortion-related near-miss events;
- To describe the quality of the clinical management of abortion-related complications
(including near-miss cases) and the heath facilities capacity to manage these complications
- To describe the experiences of women who present as near-miss cases, including their
decision-making processes, access, pathways to care as well as conditions and factors that
could contribute to the life-threatening conditions and near-miss event.
- To describe the knowledge, attitudes, practices, and behaviors of health care workers in
relation to abortion;
- To describe the characteristics, management, outcomes of ectopic and molar pregnancies
ClinicalTrials.gov: NCT04331847
Journal Article > ResearchFull Text
Clin Pharmacol Ther
Clinical Pharmacology and Therapeutics. 2019 June 1
Chotsiri P, Denoeud-Ndam L, Baudin E, Guindo O, Diawara H, et al.
Clin Pharmacol Ther
Clinical Pharmacology and Therapeutics. 2019 June 1
Severe acute malnutrition (SAM) has been reported to be associated with increased malaria morbidity in Sub‐Saharan African children and may affect the pharmacology of antimalarial drugs. This population pharmacokinetic‐pharmacodynamic study included 131 SAM and 266 non‐SAM children administered artemether‐lumefantrine twice daily for 3 days. Lumefantrine capillary plasma concentrations were adequately described by two transit‐absorption compartments followed by two distribution compartments. Allometrically scaled body weight and an enzymatic maturation effect were included in the pharmacokinetic model. Mid‐upper arm circumference (MUAC) was associated with decreased absorption of lumefantrine (25.4% decrease per 1 cm reduction). Risk of recurrent malaria episodes (i.e. reinfection) were characterised by an interval‐censored time‐to‐event model with a sigmoid EMAX‐model describing the effect of lumefantrine. SAM children were at risk of under‐exposure to lumefantrine and an increased risk of malaria reinfection compared to well‐nourished children. Research on optimised regimens should be considered for malaria treatment in malnourished children.
Conference Material > Abstract
Chen H, Fetters T, Ngbale NR, Nguengo L, Dodane T, et al.
MSF Scientific Days International 2021: Research. 2021 May 18
INTRODUCTION
Abortion-related complications remain a major cause of maternal mortality worldwide. The Castor Maternity Unit (CMU) in Bangui, CAR, serves nearly 500,000 people affected by chronic armed conflict. The country’s maternal mortality ratio (890/100,000 live births) is among the world’s highest. Abortion-related complications are a major cause of maternal death in the country and a substantial contributor to CMU admissions. To understand factors contributing to the magnitude and severity of abortion complications in this setting, we carried out a knowledge, attitudes, practices, and behavior (KAPB) survey among CMU health professionals.
METHODS
A cross-sectional quantitative survey was done using a self-administered questionnaire to all physicians, midwives, and nurses providing post-abortion care (PAC) in CMU, asking questions about PAC, contraception, and safe abortion care (SAC). We used descriptive analysis to present frequencies and proportions.
ETHICS
This study was approved by the CAR Ethics Committee, the Institutional Review Board of the Guttmacher Institute, and the MSF Ethics Review Board.
RESULTS
The provider response rate was 94% (84/89). Personal experience with unsafe abortion was common: 89% (n=75) of respondents knew someone personally who had died from an unsafe abortion. Almost 70% (n=56) considered access to SAC to be every woman’s right. Correct knowledge of the legality of abortion in CAR varied between 48-80% (n=40-67). Most of the respondents (n=47; 56%) reported having referred at least one woman for SAC. A question about providers’ conscientious objections to providing SAC found that 76% (n=59) noted strong agreement with the statement that health professionals should refer patients to another provider if they had objections to SAC provision. More than 90% (n=75) considered PAC to be every woman’s right. Despite a significant caseload of severe complications linked with abortion, only 21% of respondents (n=18) correctly identified the WHO near-miss criteria, which diagnose very severe abortion complications. Additionally, while dilatation and curettage is currently not recommended by clinical guidelines, 44% of respondents providing PAC (n=27) stated they were still using this method, at least some of the time. Contraception was provided by 85% of respondents (n=71) without issue but a smaller proportion (n=49; 59%) stated overt support when asked if they would provide contraception to minors without parental consent. While 76% (n=64) of respondents were trained in implant insertion, only 30% (n=26) were trained in inserting intrauterine devices.
CONCLUSION
CMU healthcare professionals were generally supportive of PAC, contraception and SAC. Nevertheless, we still found shortcomings in their knowledge and practices. Although limited by small sample size, the high response rate does permit drawing recommendations for this maternity unit. Innovative approaches for continuing education and capacity-building are needed, which could include workshops exploring values and attitudes about abortion, alongside efforts to simplify near-miss approaches, and training on all contraception methods to provide for women’s personal preferences. These could improve the facility towards provision of the full range of comprehensive abortion care.
CONFLICTS OF INTEREST
None declared.
Abortion-related complications remain a major cause of maternal mortality worldwide. The Castor Maternity Unit (CMU) in Bangui, CAR, serves nearly 500,000 people affected by chronic armed conflict. The country’s maternal mortality ratio (890/100,000 live births) is among the world’s highest. Abortion-related complications are a major cause of maternal death in the country and a substantial contributor to CMU admissions. To understand factors contributing to the magnitude and severity of abortion complications in this setting, we carried out a knowledge, attitudes, practices, and behavior (KAPB) survey among CMU health professionals.
METHODS
A cross-sectional quantitative survey was done using a self-administered questionnaire to all physicians, midwives, and nurses providing post-abortion care (PAC) in CMU, asking questions about PAC, contraception, and safe abortion care (SAC). We used descriptive analysis to present frequencies and proportions.
ETHICS
This study was approved by the CAR Ethics Committee, the Institutional Review Board of the Guttmacher Institute, and the MSF Ethics Review Board.
RESULTS
The provider response rate was 94% (84/89). Personal experience with unsafe abortion was common: 89% (n=75) of respondents knew someone personally who had died from an unsafe abortion. Almost 70% (n=56) considered access to SAC to be every woman’s right. Correct knowledge of the legality of abortion in CAR varied between 48-80% (n=40-67). Most of the respondents (n=47; 56%) reported having referred at least one woman for SAC. A question about providers’ conscientious objections to providing SAC found that 76% (n=59) noted strong agreement with the statement that health professionals should refer patients to another provider if they had objections to SAC provision. More than 90% (n=75) considered PAC to be every woman’s right. Despite a significant caseload of severe complications linked with abortion, only 21% of respondents (n=18) correctly identified the WHO near-miss criteria, which diagnose very severe abortion complications. Additionally, while dilatation and curettage is currently not recommended by clinical guidelines, 44% of respondents providing PAC (n=27) stated they were still using this method, at least some of the time. Contraception was provided by 85% of respondents (n=71) without issue but a smaller proportion (n=49; 59%) stated overt support when asked if they would provide contraception to minors without parental consent. While 76% (n=64) of respondents were trained in implant insertion, only 30% (n=26) were trained in inserting intrauterine devices.
CONCLUSION
CMU healthcare professionals were generally supportive of PAC, contraception and SAC. Nevertheless, we still found shortcomings in their knowledge and practices. Although limited by small sample size, the high response rate does permit drawing recommendations for this maternity unit. Innovative approaches for continuing education and capacity-building are needed, which could include workshops exploring values and attitudes about abortion, alongside efforts to simplify near-miss approaches, and training on all contraception methods to provide for women’s personal preferences. These could improve the facility towards provision of the full range of comprehensive abortion care.
CONFLICTS OF INTEREST
None declared.
Other > Pre-Print
Res Sq. 2023 March 20; DOI:10.21203/rs.3.rs-2671712/v1
Moore AM, Pasquier E, Williams TN, Fetters T, Powell B, et al.
Res Sq. 2023 March 20; DOI:10.21203/rs.3.rs-2671712/v1
BACKGROUND
Conducting abortion research in fragile settings presents challenges, many of which are present in other low-resourced settings to various degrees but when appearing all together, collectively served to create a set of barriers to collecting data that required creative adaptations to address and even then, we could not overcome all of them.
RESULTS
Challenges that we experienced in the course of this mixed methods research project included limited access to the study sites by research team members, research being delayed to prioritize life-saving priorities which must take precedence when resource constraints mean that both cannot be carried out, a population skeptical of participating in research due to having negative experiences with the state/other actors as well as due to being research-naïve, geographic and language constraints impacting participant recruitment because of the fact that people are coming from various displaced locations to a particular health facility, a low literacy population meant that they could not read the consent form and due to the stigmatized subject matter we did not want a family member consenting them, and respondents’ challenges participating around the time of discharge because respondents needed to travel home with family members.
CONCLUSIONS
These strategies are relevant not only to abortion research but also other research in resource-constrained/fragile and conflict-affected contexts. Improving the health of the most vulnerable can only be done through understanding barriers to care in insecure and challenging environments. Recommendations include to plan for offsite and long-distance training, supervision, and quality assurance; attempt to negotiate flexible timelines with donors; hire field staff whose only responsibility is data collection; where possible, find a way to include the most vulnerable members of the study population; adapt informed consent processes for low literacy populations; and consider including travel support for respondents. Iterating improvements in data collection innovations in these contexts will advance the field by spurring more research upon which to base policy and practices.
Conducting abortion research in fragile settings presents challenges, many of which are present in other low-resourced settings to various degrees but when appearing all together, collectively served to create a set of barriers to collecting data that required creative adaptations to address and even then, we could not overcome all of them.
RESULTS
Challenges that we experienced in the course of this mixed methods research project included limited access to the study sites by research team members, research being delayed to prioritize life-saving priorities which must take precedence when resource constraints mean that both cannot be carried out, a population skeptical of participating in research due to having negative experiences with the state/other actors as well as due to being research-naïve, geographic and language constraints impacting participant recruitment because of the fact that people are coming from various displaced locations to a particular health facility, a low literacy population meant that they could not read the consent form and due to the stigmatized subject matter we did not want a family member consenting them, and respondents’ challenges participating around the time of discharge because respondents needed to travel home with family members.
CONCLUSIONS
These strategies are relevant not only to abortion research but also other research in resource-constrained/fragile and conflict-affected contexts. Improving the health of the most vulnerable can only be done through understanding barriers to care in insecure and challenging environments. Recommendations include to plan for offsite and long-distance training, supervision, and quality assurance; attempt to negotiate flexible timelines with donors; hire field staff whose only responsibility is data collection; where possible, find a way to include the most vulnerable members of the study population; adapt informed consent processes for low literacy populations; and consider including travel support for respondents. Iterating improvements in data collection innovations in these contexts will advance the field by spurring more research upon which to base policy and practices.
Other > Pre-Print
F1000Research. 2019 February 8; Volume 8; 169.; DOI:10.12688/f1000research.17776.1
Baudin E, Bhatt NB, Rouzioux C, Serafini M, Molfino L, et al.
F1000Research. 2019 February 8; Volume 8; 169.; DOI:10.12688/f1000research.17776.1
BACKGROUND
In the CARINEMO ANRS 12146 clinical trial, HIV-tuberculosis co-infected patients in Mozambique were randomized to nevirapine (NVP) or to efavirenz (EFV)-based antiretroviral therapy to compare these two non-nucleoside reverse transcriptase inhibitors (NNRTIs) in treatment naïve patients.
METHODS
In this sub study, we explored the relationship of NNRTI concentrations with virological escape and the possible emergence of resistance mutations at week 48. The virological escape was defined as an HIV-RNA above 400 copies/m at week 48.
RESULTS
Among the 570 randomized patients, 470 (82%) had an HIV-RNA result at week 48; 54 (12.1%) patients had a viral escape and 35 patients had at least one major resistance mutation detected. Low drug concentration at weeks 12 and 24 (below the 10th percentile) were independently associated with virologic escape at week 48 (adjusted odds ratio [aOR]=2.9; 95% CI: 1.1 -7.2; p=0.0312 and aOR=4.2; 95% CI: 1.8-9.8; p=0.0019, respectively), and independently associated with an increased risk of emergence of resistance mutation (aOR=4.5; 95% CI: 1.8-14.6; p=0.009 at week 12; aOR=5.1; 95% CI: 1.8-14.6 at week 24). Receiver operating characteristic curves analyses indicated a better predictability of the mid-dose concentration and of the HIV-1 RNA values on resistance mutations in contrast to virological escape.
CONCLUSIONS
Very low drug plasma concentrations early after treatment initiation (week 12) were predictive factors of virological escape and the emergence of resistance mutations at week 48, and early monitoring of drug intake may prevent the occurrence of late virological escape and the selection of vial resistance mutations.
In the CARINEMO ANRS 12146 clinical trial, HIV-tuberculosis co-infected patients in Mozambique were randomized to nevirapine (NVP) or to efavirenz (EFV)-based antiretroviral therapy to compare these two non-nucleoside reverse transcriptase inhibitors (NNRTIs) in treatment naïve patients.
METHODS
In this sub study, we explored the relationship of NNRTI concentrations with virological escape and the possible emergence of resistance mutations at week 48. The virological escape was defined as an HIV-RNA above 400 copies/m at week 48.
RESULTS
Among the 570 randomized patients, 470 (82%) had an HIV-RNA result at week 48; 54 (12.1%) patients had a viral escape and 35 patients had at least one major resistance mutation detected. Low drug concentration at weeks 12 and 24 (below the 10th percentile) were independently associated with virologic escape at week 48 (adjusted odds ratio [aOR]=2.9; 95% CI: 1.1 -7.2; p=0.0312 and aOR=4.2; 95% CI: 1.8-9.8; p=0.0019, respectively), and independently associated with an increased risk of emergence of resistance mutation (aOR=4.5; 95% CI: 1.8-14.6; p=0.009 at week 12; aOR=5.1; 95% CI: 1.8-14.6 at week 24). Receiver operating characteristic curves analyses indicated a better predictability of the mid-dose concentration and of the HIV-1 RNA values on resistance mutations in contrast to virological escape.
CONCLUSIONS
Very low drug plasma concentrations early after treatment initiation (week 12) were predictive factors of virological escape and the emergence of resistance mutations at week 48, and early monitoring of drug intake may prevent the occurrence of late virological escape and the selection of vial resistance mutations.
Journal Article > ResearchFull Text
Antimicrob Agents Chemother. 2014 March 24; Volume 58 (Issue 6); 3182-90.; DOI:10.1128/AAC.02379-13
Bhatt NB, Barau C, Amin A, Baudin E, Meggi B, et al.
Antimicrob Agents Chemother. 2014 March 24; Volume 58 (Issue 6); 3182-90.; DOI:10.1128/AAC.02379-13
This is a substudy of the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146-CARINEMO) trial, which assessed the pharmacokinetics of rifampin or isoniazid with or without the coadministration of nonnucleoside reverse transcriptase inhibitor-based HIV antiretroviral therapy in HIV-tuberculosis-coinfected patients in Mozambique. Thirty-eight patients on antituberculosis therapy based on rifampin and isoniazid participated in the substudy (57.9% males; median age, 33 years; median weight, 51.9 kg; median CD4(+) T cell count, 104 cells/μl; median HIV-1 RNA load, 5.5 log copies/ml). The daily doses of rifampin and isoniazid were 10 and 5 mg/kg of body weight, respectively. Twenty-one patients received 200 mg of nevirapine twice a day (b.i.d.), and 17 patients received 600 mg of efavirenz once a day (q.d.) in combination with lamivudine and stavudine from day 1 until the end of the study. Blood samples were collected at regular time-dosing intervals after morning administration of a fixed-dose combination of rifampin and isoniazid. When rifampin was administered alone, the median maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve (AUC) at steady state were 6.59 mg/liter (range, 2.70 to 14.07 mg/liter) and 27.69 mg · h/liter (range, 11.41 to 109.75 mg · h/liter), respectively. Concentrations remained unchanged when rifampin was coadministered with nevirapine or efavirenz. When isoniazid was administered alone, the median isoniazid Cmax and AUC at steady state were 5.08 mg/liter (range, 1.26 to 11.51 mg/liter) and 20.92 mg · h/liter (range, 7.73 to 56.95 mg · h/liter), respectively. Concentrations remained unchanged when isoniazid was coadministered with nevirapine; however, a 29% decrease in the isoniazid AUC was observed when isoniazid was combined with efavirenz. The pharmacokinetic parameters of rifampin and isoniazid when coadministered with nevirapine or efavirenz were not altered to a clinically significant extent in these severely immunosuppressed HIV-infected patients. Patients experienced favorable clinical outcomes. (This study has been registered at ClinicalTrials.gov under registration no. NCT00495326.).