Journal Article > ResearchFull Text
Infect Agent Cancer. 2018 January 19; Volume 13 (Issue 1); DOI:10.1186/s13027-018-0177-6
Fardhdiani V, Molfino L, Zamudio AG, Manuel R, Luciano G, et al.
Infect Agent Cancer. 2018 January 19; Volume 13 (Issue 1); DOI:10.1186/s13027-018-0177-6
Kaposi's sarcoma (KS) is a common HIV-associated malignancy associated with disability, pain and poor outcomes. The cornerstone of its treatment is antiretroviral therapy, but advanced disease necessitates the addition of chemotherapy. In high-income settings, this often consists of liposomal anthracyclines, but in Mozambique, the first line includes conventional doxorubicin, bleomycin and vincristine, which is poorly-tolerated. Médecins Sans Frontières supports the Ministry of Health (MOH) in a specialized HIV and KS treatment center at the Centro de Referencia de Alto Maé in Maputo.
Journal Article > ResearchFull Text
AIDS. 2018 November 16; Volume 33 (Issue 2); DOI:10.1097/QAD.0000000000002070
Loarec A, Carnimeo V, Molfino L, Kizito W, Muyindike WR, et al.
AIDS. 2018 November 16; Volume 33 (Issue 2); DOI:10.1097/QAD.0000000000002070
: A multicentric, retrospective case-series analysis (facility-based) in five sites across Kenya, Malawi, Mozambique, and Uganda screened HIV-positive adults for hepatitis C virus (HCV) antibodies using Oraquick rapid testing and viral confirmation (in three sites). Results found substantially lower prevalence than previously reported for these countries compared with previous reports, suggesting that targeted integration of HCV screening in African HIV programs may be more impactful than routine screening.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
Journal Article > ResearchFull Text
Vaccine. 2006 May 29; Volume 24 (Issue 22); 4890-4895.; DOI:10.1016/j.vaccine.2005.10.006
Cavailler P, Perroud V, Mcchesney M, Ampuero S, Guerin PJ, et al.
Vaccine. 2006 May 29; Volume 24 (Issue 22); 4890-4895.; DOI:10.1016/j.vaccine.2005.10.006
We conducted a study to assess the feasibility and the potential vaccine coverage of a mass vaccination campaign using a two-dose oral cholera vaccine in an urban endemic neighbourhood of Beira, Mozambique. The campaign was conducted from December 2003 to January 2004. Overall 98,152 doses were administered, and vaccine coverage of the target population was 58.6% and 53.6% for the first and second rounds, respectively. The direct cost of the campaign, which excludes the price of the vaccine, amounted to slightly over 90,000 dollars, resulting in the cost per fully vaccinated person of 2.09 dollars, which is relatively high. However, in endemic settings where outbreaks are likely to occur, integrating cholera vaccination into the routine activities of the public health system could reduce such costs.
Journal Article > ResearchFull Text
AIDS Res Treat. 2013 July 17; Volume 2013 (Issue 937456); 1-8.; DOI: 10.1155/2013/937456
Geelhoed D, Decroo T, Dezembro S, Matias H, Lessitala F, et al.
AIDS Res Treat. 2013 July 17; Volume 2013 (Issue 937456); 1-8.; DOI: 10.1155/2013/937456
Mozambique continues to face many challenges in HIV and maternal and child health care (MCH). Community-based antiretroviral treatment groups (CAG) enhance retention to care among members, but whether such benefits extend to their families and to MCH remains unclear. In 2011 we studied utilization of HIV and MCH services among CAG members and their family aggregates in Changara, Mozambique, through a mixed-method assessment. We systematically revised all patient-held health cards from CAG members and their non-CAG family aggregate members and conducted semistructured group discussions on MCH topics. Quantitative data were analysed in EPI-Info. Qualitative data were manually thematically analysed. Information was retrieved from 1,624 persons, of which 420 were CAG members (26%). Good compliance with HIV treatment among CAG members was shared with non-CAG HIV-positive family members on treatment, but many family aggregate members remained without testing, and, when HIV positive, without HIV treatment. No positive effects from the CAG model were found for MCH service utilization. Barriers for utilization mentioned centred on insufficient knowledge, limited community-health facility collaboration, and structural health system limitations. CAG members were open to include MCH in their groups, offering the possibility to extend patient involvement to other health needs. We recommend that lessons learnt from HIV-based activism, patient involvement, and community participation are applied to broader SRH services, including MCH care.
Journal Article > ResearchFull Text
Int J Infect Dis. 2022 September 1; Volume 122; 215-221.; DOI:10.1016/j.ijid.2022.05.039
Zheng Q, Luquero FJ, Ciglenecki I, Wamala JF, Abubakar A, et al.
Int J Infect Dis. 2022 September 1; Volume 122; 215-221.; DOI:10.1016/j.ijid.2022.05.039
BACKGROUND
Cholera remains a public health threat but is inequitably distributed across sub-Saharan Africa. Lack of standardized reporting and inconsistent outbreak definitions limit our understanding of cholera outbreak epidemiology.
METHODS
From a database of cholera incidence and mortality, we extracted data from sub-Saharan Africa and reconstructed outbreaks of suspected cholera starting in January 2010 to December 2019 based on location-specific average weekly incidence rate thresholds. We then described the distribution of key outbreak metrics.
RESULTS
We identified 999 suspected cholera outbreaks in 744 regions across 25 sub-Saharan African countries. The outbreak periods accounted for 1.8 billion person-months (2% of the total during this period) from January 2010 to January 2020. Among 692 outbreaks reported from second-level administrative units (e.g., districts), the median attack rate was 0.8 per 1000 people (interquartile range (IQR), 0.3-2.4 per 1000), the median epidemic duration was 13 weeks (IQR, 8-19), and the median early outbreak reproductive number was 1.8 (range, 1.1-3.5). Larger attack rates were associated with longer times to outbreak peak, longer epidemic durations, and lower case fatality risks.
CONCLUSIONS
This study provides a baseline from which the progress toward cholera control and essential statistics to inform outbreak management in sub-Saharan Africa can be monitored.
Cholera remains a public health threat but is inequitably distributed across sub-Saharan Africa. Lack of standardized reporting and inconsistent outbreak definitions limit our understanding of cholera outbreak epidemiology.
METHODS
From a database of cholera incidence and mortality, we extracted data from sub-Saharan Africa and reconstructed outbreaks of suspected cholera starting in January 2010 to December 2019 based on location-specific average weekly incidence rate thresholds. We then described the distribution of key outbreak metrics.
RESULTS
We identified 999 suspected cholera outbreaks in 744 regions across 25 sub-Saharan African countries. The outbreak periods accounted for 1.8 billion person-months (2% of the total during this period) from January 2010 to January 2020. Among 692 outbreaks reported from second-level administrative units (e.g., districts), the median attack rate was 0.8 per 1000 people (interquartile range (IQR), 0.3-2.4 per 1000), the median epidemic duration was 13 weeks (IQR, 8-19), and the median early outbreak reproductive number was 1.8 (range, 1.1-3.5). Larger attack rates were associated with longer times to outbreak peak, longer epidemic durations, and lower case fatality risks.
CONCLUSIONS
This study provides a baseline from which the progress toward cholera control and essential statistics to inform outbreak management in sub-Saharan Africa can be monitored.
Journal Article > Meta-AnalysisAbstract
Int Health. 2013 July 30; Volume 5 (Issue 3); DOI:10.1093/inthealth/iht016
Decroo T, Rasschaert F, Telfer B, Remartinez D, Laga M, et al.
Int Health. 2013 July 30; Volume 5 (Issue 3); DOI:10.1093/inthealth/iht016
In sub-Saharan Africa models of care need to adapt to support continued scale up of antiretroviral therapy (ART) and retain millions in care. Task shifting, coupled with community participation has the potential to address the workforce gap, decongest health services, improve ART coverage, and to sustain retention of patients on ART over the long-term. The evidence supporting different models of community participation for ART care, or community-based ART, in sub-Saharan Africa, was reviewed. In Uganda and Kenya community health workers or volunteers delivered ART at home. In Mozambique people living with HIV/AIDS (PLWHA) self-formed community-based ART groups to deliver ART in the community. These examples of community ART programs made treatment more accessible and affordable. However, to achieve success some major challenges need to be overcome: first, community programs need to be driven, owned by and embedded in the communities. Second, an enabling and supportive environment is needed to ensure that task shifting to lay staff and PLWHA is effective and quality services are provided. Finally, a long term vision and commitment from national governments and international donors is required. Exploration of the cost, effectiveness, and sustainability of the different community-based ART models in different contexts will be needed.
Conference Material > Abstract
Lissouba P, Huerga H, Rucker C
Epicentre Scientific Day Paris 2021. 2021 June 10
BACKGROUND
The novel point-of-care urine-based FujiLAM test is promising for diagnosis of tuberculosis. We assessed the diagnostic yield of FujiLAM in HIV patients and the feasibility of using the test.
METHODS
We conducted a prospective diagnostic study and a mixed-methods feasibility and acceptability study in 4 countries: Uganda, Kenya,
Mozambique and South Africa. The diagnostic study included 2 groups of ambulatory HIV-positive adults: 1) with TB symptoms, 2) with advanced HIV disease and no TB symptoms. Patients received FujiLAM and AlereLAM, Xpert MTB/RIF, culture and chest X-ray. The feasibility study included test’ users, key informants and patients who participated through standard questionnaires, individual interviews and group discussions.
RESULTS
We included 1117 patients in the diagnostic study: 712 with TB symptoms (Group 1) and 405 with advanced HIV disease and no TB
symptoms (Group 2). TB was confirmed in 9.2% (63/685) and 4.1% (16/395) in Group 1 and 2, respectively. FujiLAM diagnostic yield among patients with confirmed TB was 63.2% and 43.8% in Group 1 and 2, respectively. FujiLAM diagnostic yield by CD4 count was: 75.0% in CD4<200, 77.8% in CD4 200-349, 31.3% in CD4≥350 (Group 1) and 46.7% in CD4<200 (Group 2). Most of the test users (including lay health workers) found FujiLAM easy to perform. The main concern was the multiple timed steps involved. Invalid results were obtained if test cartridges were dropped or performed on blood stained or cloudy urine. Most patients viewed urine sampling
positively and easier than sputum provision.
CONCLUSIONS
FujiLAM detects TB in a high proportion of the HIV patients with confirmed TB who have symptoms of TB and low CD4 counts, and in
a considerable proportion of those asymptomatic. The test is easy to perform at point-of-care. Urine sampling is well accepted by patients. These results encourage the future use of the FujiLAM assay.
KEY MESSAGES: The novel urine-based FujiLAM is a useful and easy to use point-of care test for TB diagnosis in HIV-positive patients. Urine sampling is well accepted.
This abstract is not to be quoted for publication.
The novel point-of-care urine-based FujiLAM test is promising for diagnosis of tuberculosis. We assessed the diagnostic yield of FujiLAM in HIV patients and the feasibility of using the test.
METHODS
We conducted a prospective diagnostic study and a mixed-methods feasibility and acceptability study in 4 countries: Uganda, Kenya,
Mozambique and South Africa. The diagnostic study included 2 groups of ambulatory HIV-positive adults: 1) with TB symptoms, 2) with advanced HIV disease and no TB symptoms. Patients received FujiLAM and AlereLAM, Xpert MTB/RIF, culture and chest X-ray. The feasibility study included test’ users, key informants and patients who participated through standard questionnaires, individual interviews and group discussions.
RESULTS
We included 1117 patients in the diagnostic study: 712 with TB symptoms (Group 1) and 405 with advanced HIV disease and no TB
symptoms (Group 2). TB was confirmed in 9.2% (63/685) and 4.1% (16/395) in Group 1 and 2, respectively. FujiLAM diagnostic yield among patients with confirmed TB was 63.2% and 43.8% in Group 1 and 2, respectively. FujiLAM diagnostic yield by CD4 count was: 75.0% in CD4<200, 77.8% in CD4 200-349, 31.3% in CD4≥350 (Group 1) and 46.7% in CD4<200 (Group 2). Most of the test users (including lay health workers) found FujiLAM easy to perform. The main concern was the multiple timed steps involved. Invalid results were obtained if test cartridges were dropped or performed on blood stained or cloudy urine. Most patients viewed urine sampling
positively and easier than sputum provision.
CONCLUSIONS
FujiLAM detects TB in a high proportion of the HIV patients with confirmed TB who have symptoms of TB and low CD4 counts, and in
a considerable proportion of those asymptomatic. The test is easy to perform at point-of-care. Urine sampling is well accepted by patients. These results encourage the future use of the FujiLAM assay.
KEY MESSAGES: The novel urine-based FujiLAM is a useful and easy to use point-of care test for TB diagnosis in HIV-positive patients. Urine sampling is well accepted.
This abstract is not to be quoted for publication.
Conference Material > Abstract
Arago M, Mangue M, Cumbi N, Zamudio AG, Loarec A, et al.
MSF Scientific Days International 2021: Innovation. 2021 May 20
WHAT CHALLENGE OR OPPORTUNITY DID YOU TRY TO ADDRESS? WERE EXISTING SOLUTIONS NOT AVAILABLE OR NOT GOOD ENOUGH?
Ototoxicity is an unfortunate side-effect of second-line injectable drugs for drug-resistant tuberculosis (DRTB), including aminoglycosides and peptides. Worldwide, up to 15% of patients on treatment regimens containing these drugs develop a degree of ototoxicity. Patients who experience ototoxicity are generally switched to an oral treatment regimen. Although regular audiological evaluations are recommended for patients receiving these drugs, there is limited access to these services, and few patients with noticeable hearing problems are referred for confirmation and follow-up.
WHY DOES THIS CHALLENGE OR OPPORTUNITY MATTER – WHY SHOULD MSF ADDRESS IT?
Before the introduction of this digital tool, the MSF DRTB project in Mozambique had to refer patients to the Central Hospital in Maputo. This limited the number of patients screened and referred for testing, curtailing the potential to switch treatment early for those showing mild-to-moderate hearing loss.
DESCRIBE YOUR INNOVATION AND WHAT MAKES IT INNOVATIVE
In 2018, the team piloted a way to simplify monitoring of hearing using a clinically approved mobile tablet-based tool that has been found to be comparable with traditional audiometry measurements in children and adults. MSF acquired three kits of CE-marked and FDA-certified iOS-based audiometry kits from SHOEBOX® Audiometry systems. The units were comprised of calibrated headphones and tablet-based software that have acceptable accuracy (±10dB) with 90% sensitivity and specificity. The portable units were deployed in rotation in six health centres over two years; a total of 673 audiometry tests were performed in MSF-supported public health centres in Maputo. Patients were tested at baseline during their first consultation and then monthly while on treatment regimens that included injectable drugs.
WHO WILL BENEFIT (WHOSE LIFE / WORK WILL IT IMPROVE?) AND WERE THEY INVOLVED IN THE DESIGN?
The 2018 Mozambique National TB Committee approved treatment without injectable drugs in patients who had any degree of hearing impairment before the initiation of treatment. Patients screened using the digital tool directly benefitted from switching to oral DRTB treatment if they exhibited any hearing loss, without requiring hospital referral.
WHAT OBJECTIVES DID YOU SET FOR THE PROJECT – WHAT DID YOU WANT TO ACHIEVE AND HOW DID YOU DEFINE AND MEASURE SUCCESS (IMPROVED SERVICE, LOWER COST, BETTER EFFICIENCY, BETTER USER EXPERIENCE, ETC.)?
We describe the implementation and use of a mobile audiometry system for patients with treatment-related ototoxicity in the MSF DRTB project in Mozambique, and consider its potential for easily assessing hearing deterioration in this cohort.
WHAT DATA DID YOU COLLECT TO MEASURE THE INNOVATION AGAINST THESE INDICATORS AND HOW DID YOU COLLECT IT? INCLUDE IF YOU DECIDED TO CHANGE THE INDICATORS AND WHY
Routinely collected data were evaluated.
WERE THERE ANY LIMITATIONS TO THE DATA YOU COLLECTED, HOW YOU COLLECTED IT OR HOW YOU ANALYSED IT, OR WERE THERE ANY UNFORESEEN FACTORS THAT MAY HAVE INTERFERED WITH YOUR RESULTS?
Data were analysed retrospectively from routine records and may not be exhaustive. Separate analysis of baseline and follow-up was not possible.
WHAT RESULTS DID YOU GET?
Of the 673 audiometry tests conducted using the digital tool, 480 (71%) showed normal hearing, 65 (10%) mild hearing loss, 81 (12%) moderate hearing loss, and 47 (7%) severe-to-profound hearing loss.
COMPARING THE RESULTS FROM YOUR DATA ANALYSIS TO YOUR OBJECTIVES, EXPLAIN WHY YOU CONSIDER YOUR INNOVATION A SUCCESS OR FAILURE?
This decentralised approach does not need specialised setup, which may lead to increased screening, proper follow-up, and more potential for early switching of drug regimens.
TO WHAT EXTENT DID THE INNOVATION BENEFIT PEOPLE’S LIVES / WORK?
Decreasing the need for hospital referrals improved time and transport costs for patients.
IS THERE ANYTHING THAT YOU WOULD DO DIFFERENTLY IF YOU WERE TO DO THE WORK AGAIN?:
A cost-benefit analysis to compare the mobile audiometry system to referrals would be beneficial for programmatic decisions.
WHAT ARE THE NEXT STEPS FOR THE INNOVATION ITSELF (SCALE UP, IMPLEMENTATION, FURTHER DEVELOPMENT, DISCONTINUED)?
In December 2019, the project was phased out as there was a protocol change in which injectable drugs were replaced with more potent and fully oral regimens that made monitoring for ototoxicity unnecessary for most patients.
IS THE INNOVATION TRANSFERABLE OR ADAPTABLE TO OTHER SETTINGS OR DOMAINS?
The tools adapted are clinically approved for screening activities for any programmes that deal with hearing loss.
WHAT BROADER IMPLICATIONS ARE THERE FROM THE INNOVATION FOR MSF AND / OR OTHERS (CHANGE IN PRACTICE, CHANGE IN POLICY, CHANGE IN GUIDELINES, PARADIGM SHIFT)?
The project demonstrates the potential to improve follow-up and detect complications early for patients who take ototoxic medications.
WHAT OTHER LEARNINGS FROM YOUR WORK ARE IMPORTANT TO SHARE?
User-friendly and automated audiometry systems that are mobile and do not require audiologists or sound-insulated booths could be extremely useful to various medical projects using potentially ototoxic drugs such as aminoglycosides. They may also be beneficial for environmental projects with noise and toxic pollutions. The high cost of the license could present a limitation necessitating a cost-benefit analysis before contemplating scale-up.
ETHICS
This description and evaluation of an innovation project involved human participants or their data, and has had ethics oversight from Monica Rull, Medical Director, Operational Centre Geneva, MSF.
Ototoxicity is an unfortunate side-effect of second-line injectable drugs for drug-resistant tuberculosis (DRTB), including aminoglycosides and peptides. Worldwide, up to 15% of patients on treatment regimens containing these drugs develop a degree of ototoxicity. Patients who experience ototoxicity are generally switched to an oral treatment regimen. Although regular audiological evaluations are recommended for patients receiving these drugs, there is limited access to these services, and few patients with noticeable hearing problems are referred for confirmation and follow-up.
WHY DOES THIS CHALLENGE OR OPPORTUNITY MATTER – WHY SHOULD MSF ADDRESS IT?
Before the introduction of this digital tool, the MSF DRTB project in Mozambique had to refer patients to the Central Hospital in Maputo. This limited the number of patients screened and referred for testing, curtailing the potential to switch treatment early for those showing mild-to-moderate hearing loss.
DESCRIBE YOUR INNOVATION AND WHAT MAKES IT INNOVATIVE
In 2018, the team piloted a way to simplify monitoring of hearing using a clinically approved mobile tablet-based tool that has been found to be comparable with traditional audiometry measurements in children and adults. MSF acquired three kits of CE-marked and FDA-certified iOS-based audiometry kits from SHOEBOX® Audiometry systems. The units were comprised of calibrated headphones and tablet-based software that have acceptable accuracy (±10dB) with 90% sensitivity and specificity. The portable units were deployed in rotation in six health centres over two years; a total of 673 audiometry tests were performed in MSF-supported public health centres in Maputo. Patients were tested at baseline during their first consultation and then monthly while on treatment regimens that included injectable drugs.
WHO WILL BENEFIT (WHOSE LIFE / WORK WILL IT IMPROVE?) AND WERE THEY INVOLVED IN THE DESIGN?
The 2018 Mozambique National TB Committee approved treatment without injectable drugs in patients who had any degree of hearing impairment before the initiation of treatment. Patients screened using the digital tool directly benefitted from switching to oral DRTB treatment if they exhibited any hearing loss, without requiring hospital referral.
WHAT OBJECTIVES DID YOU SET FOR THE PROJECT – WHAT DID YOU WANT TO ACHIEVE AND HOW DID YOU DEFINE AND MEASURE SUCCESS (IMPROVED SERVICE, LOWER COST, BETTER EFFICIENCY, BETTER USER EXPERIENCE, ETC.)?
We describe the implementation and use of a mobile audiometry system for patients with treatment-related ototoxicity in the MSF DRTB project in Mozambique, and consider its potential for easily assessing hearing deterioration in this cohort.
WHAT DATA DID YOU COLLECT TO MEASURE THE INNOVATION AGAINST THESE INDICATORS AND HOW DID YOU COLLECT IT? INCLUDE IF YOU DECIDED TO CHANGE THE INDICATORS AND WHY
Routinely collected data were evaluated.
WERE THERE ANY LIMITATIONS TO THE DATA YOU COLLECTED, HOW YOU COLLECTED IT OR HOW YOU ANALYSED IT, OR WERE THERE ANY UNFORESEEN FACTORS THAT MAY HAVE INTERFERED WITH YOUR RESULTS?
Data were analysed retrospectively from routine records and may not be exhaustive. Separate analysis of baseline and follow-up was not possible.
WHAT RESULTS DID YOU GET?
Of the 673 audiometry tests conducted using the digital tool, 480 (71%) showed normal hearing, 65 (10%) mild hearing loss, 81 (12%) moderate hearing loss, and 47 (7%) severe-to-profound hearing loss.
COMPARING THE RESULTS FROM YOUR DATA ANALYSIS TO YOUR OBJECTIVES, EXPLAIN WHY YOU CONSIDER YOUR INNOVATION A SUCCESS OR FAILURE?
This decentralised approach does not need specialised setup, which may lead to increased screening, proper follow-up, and more potential for early switching of drug regimens.
TO WHAT EXTENT DID THE INNOVATION BENEFIT PEOPLE’S LIVES / WORK?
Decreasing the need for hospital referrals improved time and transport costs for patients.
IS THERE ANYTHING THAT YOU WOULD DO DIFFERENTLY IF YOU WERE TO DO THE WORK AGAIN?:
A cost-benefit analysis to compare the mobile audiometry system to referrals would be beneficial for programmatic decisions.
WHAT ARE THE NEXT STEPS FOR THE INNOVATION ITSELF (SCALE UP, IMPLEMENTATION, FURTHER DEVELOPMENT, DISCONTINUED)?
In December 2019, the project was phased out as there was a protocol change in which injectable drugs were replaced with more potent and fully oral regimens that made monitoring for ototoxicity unnecessary for most patients.
IS THE INNOVATION TRANSFERABLE OR ADAPTABLE TO OTHER SETTINGS OR DOMAINS?
The tools adapted are clinically approved for screening activities for any programmes that deal with hearing loss.
WHAT BROADER IMPLICATIONS ARE THERE FROM THE INNOVATION FOR MSF AND / OR OTHERS (CHANGE IN PRACTICE, CHANGE IN POLICY, CHANGE IN GUIDELINES, PARADIGM SHIFT)?
The project demonstrates the potential to improve follow-up and detect complications early for patients who take ototoxic medications.
WHAT OTHER LEARNINGS FROM YOUR WORK ARE IMPORTANT TO SHARE?
User-friendly and automated audiometry systems that are mobile and do not require audiologists or sound-insulated booths could be extremely useful to various medical projects using potentially ototoxic drugs such as aminoglycosides. They may also be beneficial for environmental projects with noise and toxic pollutions. The high cost of the license could present a limitation necessitating a cost-benefit analysis before contemplating scale-up.
ETHICS
This description and evaluation of an innovation project involved human participants or their data, and has had ethics oversight from Monica Rull, Medical Director, Operational Centre Geneva, MSF.
Journal Article > Meta-AnalysisFull Text
PLOS One. 2013 July 22; Volume 8 (Issue 7); e68995.; DOI:10.1371/journal.pone.0068995
Pillay P, Ford NP, Shubber Z, Ferrand RA
PLOS One. 2013 July 22; Volume 8 (Issue 7); e68995.; DOI:10.1371/journal.pone.0068995
INTRODUCTION
There is conflicting evidence and practice regarding the use of the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) and nevirapine (NVP) in first-line antiretroviral therapy (ART).
METHODS
We systematically reviewed virological outcomes in HIV-1 infected, treatment-naive patients on regimens containing EFV versus NVP from randomised trials and observational cohort studies. Data sources include PubMed, Embase, the Cochrane Central Register of Controlled Trials and conference proceedings of the International AIDS Society, Conference on Retroviruses and Opportunistic Infections, between 1996 to May 2013. Relative risks (RR) and 95% confidence intervals were synthesized using random-effects meta-analysis. Heterogeneity was assessed using the I(2) statistic, and subgroup analyses performed to assess the potential influence of study design, duration of follow up, location, and tuberculosis treatment. Sensitivity analyses explored the potential influence of different dosages of NVP and different viral load thresholds.
RESULTS
Of 5011 citations retrieved, 38 reports of studies comprising 114 391 patients were included for review. EFV was significantly less likely than NVP to lead to virologic failure in both trials (RR 0.85 [0.73-0.99] I(2) = 0%) and observational studies (RR 0.65 [0.59-0.71] I(2) = 54%). EFV was more likely to achieve virologic success than NVP, though marginally significant, in both randomised controlled trials (RR 1.04 [1.00-1.08] I(2) = 0%) and observational studies (RR 1.06 [1.00-1.12] I(2) = 68%).
CONCLUSION
EFV-based first line ART is significantly less likely to lead to virologic failure compared to NVP-based ART. This finding supports the use of EFV as the preferred NNRTI in first-line treatment regimen for HIV treatment, particularly in resource limited settings.
There is conflicting evidence and practice regarding the use of the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) and nevirapine (NVP) in first-line antiretroviral therapy (ART).
METHODS
We systematically reviewed virological outcomes in HIV-1 infected, treatment-naive patients on regimens containing EFV versus NVP from randomised trials and observational cohort studies. Data sources include PubMed, Embase, the Cochrane Central Register of Controlled Trials and conference proceedings of the International AIDS Society, Conference on Retroviruses and Opportunistic Infections, between 1996 to May 2013. Relative risks (RR) and 95% confidence intervals were synthesized using random-effects meta-analysis. Heterogeneity was assessed using the I(2) statistic, and subgroup analyses performed to assess the potential influence of study design, duration of follow up, location, and tuberculosis treatment. Sensitivity analyses explored the potential influence of different dosages of NVP and different viral load thresholds.
RESULTS
Of 5011 citations retrieved, 38 reports of studies comprising 114 391 patients were included for review. EFV was significantly less likely than NVP to lead to virologic failure in both trials (RR 0.85 [0.73-0.99] I(2) = 0%) and observational studies (RR 0.65 [0.59-0.71] I(2) = 54%). EFV was more likely to achieve virologic success than NVP, though marginally significant, in both randomised controlled trials (RR 1.04 [1.00-1.08] I(2) = 0%) and observational studies (RR 1.06 [1.00-1.12] I(2) = 68%).
CONCLUSION
EFV-based first line ART is significantly less likely to lead to virologic failure compared to NVP-based ART. This finding supports the use of EFV as the preferred NNRTI in first-line treatment regimen for HIV treatment, particularly in resource limited settings.
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).