Journal Article > ResearchFull Text
Lancet Infect Dis. 2005 December 1; Volume 5 (Issue 12); DOI:10.1016/S1473-3099(05)70296-6
Olliaro PL, Guerin PJ, Gerstl S, Haaskjold AA, Rottingen JA, et al.
Lancet Infect Dis. 2005 December 1; Volume 5 (Issue 12); DOI:10.1016/S1473-3099(05)70296-6
The state of Bihar in India carries the largest share of the world's burden of antimony-resistant visceral leishmaniasis. We analysed clinical studies done in Bihar with different treatments between 1980 and 2004. Overall, 53 studies were included (all but one published), of which 15 were comparative (randomised, quasi-randomised, or non-randomised), 23 dose-finding, and 15 non-comparative. Data from comparative studies were pooled when appropriate for meta-analysis. Overall, these studies enrolled 7263 patients in 123 treatment arms. Adequacy of methods used to do the studies and report on them varied. Unresponsiveness to antimony has developed steadily in the past to such an extent that antimony must now be replaced, despite attempts to stop its progression by increasing dose and duration of therapy. The classic second-line treatments are unsuited: pentamidine is toxic and its efficacy has also declined, and amphotericin B deoxycholate is effective but requires hospitalisation for long periods and toxicity is common. Liposomal amphotericin B is very effective and safe but currently unaffordable because of its high price. Miltefosine-the first oral drug for visceral leishmaniasis-is now registered and marketed in India and is effective, but should be used under supervision to prevent misuse. Paromomycin (or aminosidine) is effective and safe, and although not yet available, a regulatory submission is due soon. To preserve the limited armamentarium of drugs to treat visceral leishmaniasis, drugs should not be deployed unprotected; combinations can make drugs last longer, improve treatment, and reduce costs to households and health systems. India, Bangladesh, and Nepal agreed recently to undertake measures towards the elimination of visceral leishmaniasis. The lessons learnt in Bihar could help inform policy decisions both regionally and elsewhere.
Journal Article > Meta-AnalysisFull Text
Lancet Infect Dis. 2015 May 5; Volume 15 (Issue 7); DOI:10.1016/S1473-3099(15)00006-7
Rao VB, Johari N, du Cros PAK, Messina J, Ford NP, et al.
Lancet Infect Dis. 2015 May 5; Volume 15 (Issue 7); DOI:10.1016/S1473-3099(15)00006-7
An estimated 150 million people worldwide are infected with hepatitis C virus (HCV). HIV co-infection accelerates the progression of HCV and represents a major public health challenge. We aimed to determine the epidemiology of HCV and the prevalence of HIV co-infection in sub-Saharan Africa.
Journal Article > Short ReportFull Text
Lancet Infect Dis. 2018 March 13; Volume 18 (Issue 9); DOI:10.1016/S1473-3099(18)30104-X
Cox HS, Hughes J, Black JM, Nicol MP
Lancet Infect Dis. 2018 March 13; Volume 18 (Issue 9); DOI:10.1016/S1473-3099(18)30104-X
Treatment for drug-resistant tuberculosis is largely delivered through standardised, empirical combination regimens in low-resource, high-burden settings. However, individualised treatment, guided by detailed drug susceptibility testing, probably results in improved individual outcomes and is the standard of care in well-resourced settings. Driven by the urgent need to scale up treatment provision, new tuberculosis drugs, incorporated into standardised regimens, are being tested. Although standardised regimens are expected to improve access to treatment in high-burden settings, they are also likely to contribute to the emergence of resistance, even with good clinical management. We argue that a balance is required between the need to improve treatment access and the imperative to minimise resistance amplification and provide the highest standard of care, through a precision medicine approach. In tuberculosis, as in other diseases, we should aim to reduce the entrenched inequalities that manifest as different standards of care in different 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).
Journal Article > Case Report/SeriesFull Text
Lancet Infect Dis. 2024 August 1; Online ahead of print; DOI:10.1016/S1473-3099(24)00419-5
Meakin S, Nsio J, Camacho A, Kitenge R, Coulborn RM, et al.
Lancet Infect Dis. 2024 August 1; Online ahead of print; DOI:10.1016/S1473-3099(24)00419-5
BACKRGOUND
The recombinant vesicular stomatitis virus-Zaire Ebola virus (rVSV-ZEBOV) vaccine is the only WHO prequalified vaccine recommended for use to respond to outbreaks of Ebola virus (species Zaire ebolavirus) by WHO's Strategic Advisory Group of Experts on Immunization. Despite the vaccine's widespread use during several outbreaks, no real-world effectiveness estimates are currently available in the literature.
METHODS
We conducted a retrospective test-negative analysis to estimate effectiveness of rVSV-ZEBOV vaccination against Ebola virus disease during the 2018-20 epidemic in the Democratic Republic of the Congo, using data on suspected Ebola virus disease cases collected from Ebola treatment centres. Those eligible for inclusion had an available Ebola virus RT-PCR result, available key data, were eligible for vaccination during the outbreak, and had symptom onset aligning with the period in which a ring-vaccination protocol was in use. After imputing missing data, each individual confirmed by RT-PCR to be Ebola virus disease-positive (defined as a case) was matched to one individual negative for Ebola virus disease (control) by sex, age, health zone, and month of symptom onset. Effectiveness was estimated from the odds ratio of being vaccinated (≥10 days before symptom onset) versus being unvaccinated among cases and controls, after adjusting for the matching factors. The imputation, matching and effectiveness estimation, was repeated 500 times.
FINDINGS
1273 (4·8%) of 26 438 eligible individuals were positive for Ebola virus disease (cases) and 25 165 (95·2%) were negative (controls). 40 (3·1%) cases and 1271 (5·1%) controls were reported as being vaccinated at least 10 days before symptom onset. After selecting individuals who reported exposure to an individual with Ebola virus disease within the 21 days before symptom onset and matching, the analysis datasets comprised a median of 309 cases and 309 controls. 10 days or more after vaccination, the effectiveness of rVSV-ZEBOV against Ebola virus disease was estimated to be 84% (95% credible interval 70-92).
INTERPRETATION
This analysis is the first to provide estimates of the real-world effectiveness of the rVSV-ZEBOV vaccine against Ebola virus disease, amid the widespread use of the vaccine during a large Ebola virus disease outbreak. Our findings confirm that rVSV-ZEBOV is highly protective against Ebola virus disease and support its use during outbreaks, even in challenging contexts such as in the eastern Democratic Republic of the Congo.
Journal Article > CommentaryFull Text
Lancet Infect Dis. 2010 March 1; Volume 10 (Issue 3); DOI:10.1016/S1473-3099(10)70042-6
Zachariah R
Lancet Infect Dis. 2010 March 1; Volume 10 (Issue 3); DOI:10.1016/S1473-3099(10)70042-6
Journal Article > CommentaryFull Text
Lancet Infect Dis. 2021 February 12; Volume 21; DOI:10.1016/S1473-3099(20)30836-7
Hewison CCH, Guglielmetti L
Lancet Infect Dis. 2021 February 12; Volume 21; DOI:10.1016/S1473-3099(20)30836-7
We are not alone in welcoming the study by Kelly E Dooley and colleagues 1 that sheds light on the QT prolonging effects of the combination of bedaquiline and delamanid, two key drugs for the treatment of multidrug-resistant or rifampicin-resistant tuberculosis. Clinicians treating multidrug-resistant or rifampicin-resistant tuberculosis worldwide only recently started losing sleep over the fear of QT interval prolongation, a well-known adverse event of many drugs. A heart rate-corrected QT interval (QTc) of 500 ms or more increases the risk of potentially fatal ventricular arrhythmias, including torsade de pointes. 2 Despite the frequent, long-term use of QT interval-prolonging drugs, including moxifloxacin, which is used as a positive control in thorough QT studies, 3 ECG monitoring became routine during multidrug or rifampicin-resistant tuberculosis treatment only after the first phase 2 trials showed QT prolongation during treatment with bedaquiline and delamanid. These concerns initially led WHO to formulate conservative recommendations regarding their use in combination. 4 Many of these fears have since been dispelled by increasing evidence. 5 , 6 , 7 In particular, WHO guidelines, based on a review of data done in 2019 including the results of the study by Dooley and colleagues, showed no additional safety concerns related to this combination. 8
Journal Article > CommentaryAbstract
Lancet Infect Dis. 2011 April 1; Volume 11 (Issue 4); DOI:10.1016/S1473-3099(11)70036-6
Cox HS, Ford NP, Keshavjee S, McDermid C, von Schoen-Angerer T, et al.
Lancet Infect Dis. 2011 April 1; Volume 11 (Issue 4); DOI:10.1016/S1473-3099(11)70036-6
Journal Article > CommentaryFull Text
Lancet Infect Dis. 2020 April 2; Volume 20 (Issue 7); 756-757.; DOI:10.1016/S1473-3099(20)30264-4.
Azman AS, Luquero FJ
Lancet Infect Dis. 2020 April 2; Volume 20 (Issue 7); 756-757.; DOI:10.1016/S1473-3099(20)30264-4.
Journal Article > LetterFull Text
Lancet Infect Dis. 2024 April 30; Volume S1473-3099 (Issue 24); 00237-8.; DOI:10.1016/S1473-3099(24)00237-8
Finger F, Heitzinger K, Berendes D, Ciglenecki I, Dominguez M, et al.
Lancet Infect Dis. 2024 April 30; Volume S1473-3099 (Issue 24); 00237-8.; DOI:10.1016/S1473-3099(24)00237-8