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 > ResearchFull Text
BMC Infect Dis. 2013 January 22; Volume 13; 27.; DOI:10.1186/1471-2334-13-27
Bastard M, Soulinphumy K, Phimmasone P, Saadani A, Ciaffi L, et al.
BMC Infect Dis. 2013 January 22; Volume 13; 27.; DOI:10.1186/1471-2334-13-27
BACKGROUND
In April 2003, Médecins Sans Frontières launched an HIV/AIDS programme to provide free HAART to HIV-infected patients in Laos. Although HIV prevalence is estimated as low in this country, it has been increasing in the last years. This work reports the first results of an observational cohort study and it aims to identify the principal determinants of the CD4 cells evolution and to assess mortality among patients on HAART.
METHODS
We performed a retrospective database analysis on patients initiated on HAART between 2003 and 2009 (CD4<200cells/μL or WHO stage 4). We excluded from the analysis patients who were less than 16 years old and pregnant women. To explore the determinants of the CD4 reconstitution, a linear mixed model was adjusted. To identify typical trajectories of the CD4 cells, a latent trajectory analysis was carried out. Finally, a Cox proportional-hazards model was used to reveal predictors of mortality on HAART including appointment delay greater than 1 day.
RESULTS
A total of 1365 patients entered the programme and 913 (66.9%) received an HAART with a median CD4 of 49 cells/μL [IQR 15–148]. High baseline CD4 cell count and female gender were associated with a higher CD4 level over time. In addition, this gender difference increased over time. Two typical latent CD4 trajectories were revealed showing that 31% of women against 22% of men followed a high CD4 trajectory. In the long-term, women were more likely to attend appointments without delay. Mortality reached 6.2% (95% CI 4.8-8.0%) at 4 months and 9.1% (95% CI 7.3-11.3%) at 1 year. Female gender (HR=0.17, 95% CI 0.07-0.44) and high CD4 trajectory (HR=0.19, 95% CI 0.08-0.47) were independently associated with a lower death rate.
CONCLUSIONS
Patients who initiated HAART were severely immunocompromised yielding to a high early mortality. In the long-term on HAART, women achieved a better CD4 cells reconstitution than men and were less likely to die. This study highlights important differences between men and women regarding response to HAART and medical care, and questions men’s compliance to treatment.
In April 2003, Médecins Sans Frontières launched an HIV/AIDS programme to provide free HAART to HIV-infected patients in Laos. Although HIV prevalence is estimated as low in this country, it has been increasing in the last years. This work reports the first results of an observational cohort study and it aims to identify the principal determinants of the CD4 cells evolution and to assess mortality among patients on HAART.
METHODS
We performed a retrospective database analysis on patients initiated on HAART between 2003 and 2009 (CD4<200cells/μL or WHO stage 4). We excluded from the analysis patients who were less than 16 years old and pregnant women. To explore the determinants of the CD4 reconstitution, a linear mixed model was adjusted. To identify typical trajectories of the CD4 cells, a latent trajectory analysis was carried out. Finally, a Cox proportional-hazards model was used to reveal predictors of mortality on HAART including appointment delay greater than 1 day.
RESULTS
A total of 1365 patients entered the programme and 913 (66.9%) received an HAART with a median CD4 of 49 cells/μL [IQR 15–148]. High baseline CD4 cell count and female gender were associated with a higher CD4 level over time. In addition, this gender difference increased over time. Two typical latent CD4 trajectories were revealed showing that 31% of women against 22% of men followed a high CD4 trajectory. In the long-term, women were more likely to attend appointments without delay. Mortality reached 6.2% (95% CI 4.8-8.0%) at 4 months and 9.1% (95% CI 7.3-11.3%) at 1 year. Female gender (HR=0.17, 95% CI 0.07-0.44) and high CD4 trajectory (HR=0.19, 95% CI 0.08-0.47) were independently associated with a lower death rate.
CONCLUSIONS
Patients who initiated HAART were severely immunocompromised yielding to a high early mortality. In the long-term on HAART, women achieved a better CD4 cells reconstitution than men and were less likely to die. This study highlights important differences between men and women regarding response to HAART and medical care, and questions men’s compliance to treatment.
Journal Article > ResearchFull Text
HIV Med. 2010 January 1; Volume 11 (Issue 1); DOI:10.1111/j.1468-1293.2009.00742.x
Laurent C, Bourgeois A, Mpoudi-Ngole E, Kouanfack C, Ciaffi L, et al.
HIV Med. 2010 January 1; Volume 11 (Issue 1); DOI:10.1111/j.1468-1293.2009.00742.x
OBJECTIVES: To investigate the presence of hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA in HIV-infected patients initiating antiretroviral therapy in Cameroon. METHODS: Baseline blood samples from 169 patients were tested retrospectively for hepatitis B surface antigens (HBsAg), anti-hepatitis B core (anti-HBc), anti-HCV and - if HBsAg or anti-HCV result was positive or indeterminate - for HBV DNA or HCV RNA, respectively, using the Cobas Ampliprep/Cobas TaqMan quantitative assay (Roche Diagnostics GmbH, Mannheim, Germany). RESULTS: HBV DNA was detected in 14 of the 18 patients with positive or indeterminate HBsAg results [8.3% of the total study population, 95% confidence interval (CI) 4.6-13.5]. The median HBV viral load was 2.47 x 10(7) IU/mL [interquartile range (IQR) 3680-1.59 x 10(8); range 270 to >2.2 x 10(8)]. Twenty-one patients (12.4%, 95% CI 7.9-18.4) were found with HCV RNA (all with positive HCV serology). The median HCV viral load was 928 000 IU/mL (IQR 178 400-2.06 x 10(6); range 640-5.5 x 10(6)). No patient was co-infected with HBV and HCV. In multivariate analysis, HCV co-infection was associated with greater age [>or=45 years vs. <45 years, odds ratio (OR) 11.89, 95% CI 3.49-40.55, P<0.001] and abnormal serum alanine aminotransferase level [>or=1.25 x upper limit of normal (ULN) vs. <1.25 x ULN, OR 7.81, 95% CI 1.54-39.66, P=0.01]; HBV co-infection was associated with abnormal serum aspartate aminotransferase level (OR 4.33, 95% CI 1.32-14.17, P=0.02). CONCLUSIONS: These high rates of active HBV and HCV co-infections in HIV-positive Cameroonian patients requiring antiretroviral therapy underline the need to promote: (i) screening for HBV and HCV before treatment initiation; (ii) accessibility to tenofovir (especially in HBV-endemic African countries); and (iii) accessibility to treatment for HBV and HCV infections.
Journal Article > ResearchFull Text
Open Forum Infect Dis. 2014 April 26; Volume 1 (Issue 1); DOI:10.1093/ofid/ofu021
Christinet V, Rossel L, Serafini M, Delhumeau C, Odermatt P, et al.
Open Forum Infect Dis. 2014 April 26; Volume 1 (Issue 1); DOI:10.1093/ofid/ofu021
Journal Article > ResearchFull Text
Open Forum Infect Dis. 2014 May 21; Volume 1 (Issue 1); DOI:10.1093/ofid/ofu021
Christinet V, Comte E, Ciaffi L, Odermatt P, Serafini M, et al.
Open Forum Infect Dis. 2014 May 21; Volume 1 (Issue 1); DOI:10.1093/ofid/ofu021
Background: Buruli ulcer (BU) is the third most common mycobacterial disease after tuberculosis and leprosy and is particularly frequent in rural West and Central Africa. However, the impact of HIV infection on BU severity and prevalence remains unclear. Methods: This was a retrospective study of data collected at the Akonolinga district hospital, Cameroon, from 1 January 2002 to 27 March 2013. HIV prevalence among BU patients was compared to regional HIV prevalence. Baseline characteristics of BU patients were compared between HIV-negative and HIV-positive patients, and according to CD4 cell count strata in the latter group. BU time-to-healing was assessed in different CD4 count strata and factors associated with BU main lesion size at baseline were identified. Results: HIV prevalence among BU patients was significantly higher than the regional estimated prevalence in each group (children, 4.00% vs 0.68% [P < .001]; men, 17.0% vs 4.7% [P < .001]; women, 36.0% vs 8.0% [P < .001]). HIV-positive individuals had a more severe form of BU with an increased severity in those with a higher level of immunosuppression. Low CD4 cell count was significantly associated with a larger main lesion size (beta-coefficient, -0.50; P = .015; 95% confidence interval [CI], -0.91 – 0.10). BU time-to-healing was more than double in patients with a CD4 cell count below 500 cell/mm3 (hazard ratio, 2.39; P = .001, 95% CI, 1.44 - 3.98). Conclusion: HIV-positive patients are at higher risk for BU. HIV-induced immunosuppression appears to have an impact on BU clinical presentation and disease evolution.
Journal Article > ResearchFull Text
Antivir Ther. 2009 February 1; Volume 14 (Issue 3); 339-347.; DOI:10.1177/135965350901400317
Soria A, Porten K, Fampou-Toundji JC, Galli L, Mougnutou R, et al.
Antivir Ther. 2009 February 1; Volume 14 (Issue 3); 339-347.; DOI:10.1177/135965350901400317
BACKGROUND
The lack of HIV type-1 (HIV-1) viral load (VL) monitoring in resource-limited settings might favour the accumulation of resistance mutations and thus hamper second-line treatment efficacy. We investigated the factors associated with resistance after the initiation of antiretroviral therapy (ART) in the absence of virological monitoring.
METHODS
Cross-sectional VL sampling of HIV-1-infected patients receiving first-line ART (nevirapine or efavirenz plus stavudine or zidovudine plus lamivudine) was carried out; those with a detectable VL were genotyped.
RESULTS
Of the 573 patients undergoing VL sampling, 84 were genotyped. The mean number of nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) mutations increased with the duration of ART exposure (P=0.02). Multivariable analysis showed that patients with a CD4+ T-cell count < or =50 cells/mm(3) at ART initiation (baseline) had a higher mean number of both NRTI and non-NRTI (NNRTI) mutations than those with a baseline CD4+ T-cell count >50 cells/mm(3) (2.10 versus 0.56; P<0.0001; and 1.65 versus 0.76; P=0.005, respectively). A baseline CD4+ T-cell count < or =50 cells/mm(3) predicted > or =1 NRTI mutation (adjusted odds ratio [AOR] 7.49, 95% confidence interval [CI] 2.20-32.14), > or =1 NNRTI mutation (AOR 4.25, 95% CI 1.36-15.48), > or =1 thymidine analogue mutation (AOR 8.45, 95% CI 2.16-40.16) and resistance to didanosine (AOR 6.36, 95% CI 1.49-32.29) and etravirine (AOR 4.72, 95% CI 1.53-15.70).
CONCLUSIONS
Without VL monitoring, the risk of drug resistance increases with the duration of ART and is associated with lower CD4+ T-cell counts at ART initiation. These data might help define strategies to preserve second-line treatment options in resource-limited settings.
The lack of HIV type-1 (HIV-1) viral load (VL) monitoring in resource-limited settings might favour the accumulation of resistance mutations and thus hamper second-line treatment efficacy. We investigated the factors associated with resistance after the initiation of antiretroviral therapy (ART) in the absence of virological monitoring.
METHODS
Cross-sectional VL sampling of HIV-1-infected patients receiving first-line ART (nevirapine or efavirenz plus stavudine or zidovudine plus lamivudine) was carried out; those with a detectable VL were genotyped.
RESULTS
Of the 573 patients undergoing VL sampling, 84 were genotyped. The mean number of nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) mutations increased with the duration of ART exposure (P=0.02). Multivariable analysis showed that patients with a CD4+ T-cell count < or =50 cells/mm(3) at ART initiation (baseline) had a higher mean number of both NRTI and non-NRTI (NNRTI) mutations than those with a baseline CD4+ T-cell count >50 cells/mm(3) (2.10 versus 0.56; P<0.0001; and 1.65 versus 0.76; P=0.005, respectively). A baseline CD4+ T-cell count < or =50 cells/mm(3) predicted > or =1 NRTI mutation (adjusted odds ratio [AOR] 7.49, 95% confidence interval [CI] 2.20-32.14), > or =1 NNRTI mutation (AOR 4.25, 95% CI 1.36-15.48), > or =1 thymidine analogue mutation (AOR 8.45, 95% CI 2.16-40.16) and resistance to didanosine (AOR 6.36, 95% CI 1.49-32.29) and etravirine (AOR 4.72, 95% CI 1.53-15.70).
CONCLUSIONS
Without VL monitoring, the risk of drug resistance increases with the duration of ART and is associated with lower CD4+ T-cell counts at ART initiation. These data might help define strategies to preserve second-line treatment options in resource-limited settings.
Journal Article > ResearchFull Text
Euro Surveill. 2021 September 1; Volume 26 (Issue 38); 2001385.; DOI:10.2807/1560-7917.ES.2021.26.38.2001385
Giuliani R, Cairone C, Tavoschi L, Ciaffi L, Sebastiani T, et al.
Euro Surveill. 2021 September 1; Volume 26 (Issue 38); 2001385.; DOI:10.2807/1560-7917.ES.2021.26.38.2001385
Prisons are high-risk settings for COVID-19 and present specific challenges for prevention and control. We describe a COVID-19 outbreak in a large prison in Milan between 20 February and 30 April 2020. We performed a retrospective analysis of routine data collected during the COVID-19 emergency in prison. We analysed the spatial distribution of cases and calculated global and specific attack rates (AR). We assessed prevention and control measures. By 30 April 2020, 57 confirmed COVID-19 cases and 66 clinically probable cases were recorded among a population of 1,480. Global AR was 8.3%. The index case was a custodial officer. Two clusters were detected among custodial staff and healthcare workers. On 31 March, a confirmed case was identified among detained individuals. COVID-19 spread by physical proximity or among subgroups with cultural affinity, resulting in a cluster of 22 confirmed cases. Following index case identification, specific measures were taken including creation of a multidisciplinary task-force, increasing diagnostic capacity, contact tracing and dedicated isolation areas. Expanded use of personal protective equipment, environmental disinfection and health promotion activities were also implemented. Outbreaks of COVID-19 in prison require heightened attention and stringent comprehensive measures.
Journal Article > ResearchFull Text
J Acquir Immune Defic Syndr. 2008 June 1; Volume 48 (Issue 2); DOI:10.1097/QAI.0b013e3181743955
Kouanfack C, Laurent C, Peytavin G, Ciaffi L, Ngolle M, et al.
J Acquir Immune Defic Syndr. 2008 June 1; Volume 48 (Issue 2); DOI:10.1097/QAI.0b013e3181743955
OBJECTIVES: To compare adherence to antiretroviral therapy using drug level monitoring and self-report and to explore the relation between these 2 methods and viral load measurements. METHODS: Sixty patients received a fixed-dose combination of nevirapine, stavudine, and lamivudine in a clinical study in Cameroon. Adherence was assessed every 6 months until month 36 by nevirapine minimal plasma concentration and self-report. Plasma HIV-1 viral load was determined at the same time. Analyses included 159 complete observations. RESULTS: The proportion of patients labeled as "adherent" was significantly lower using nevirapine monitoring (88.7%, 95% confidence interval [CI]: 82.7 to 93.2) than self-report (97.5%, CI: 93.7 to 99.3; P = 0.002). Virologic failure was associated with the nevirapine concentration (adjusted odds ratio [aOR] = 4.43; P = 0.018) but not with the self-reported adherence (aOR = 0.84; P = 0.9). As compared with the virologic outcome, the sensitivity of nevirapine level monitoring for predicting inadequate adherence was 20.5%, the specificity was 91.7%, the positive predictive value was 44.4%, and the negative predictive value was 78.0%. For self-report, the respective values were 2.6%, 97.5%, 25.0%, and 75.5%. CONCLUSIONS: Drug level monitoring provided a more reliable estimate of adherence than self-report. This method could be used in research settings. Operational research is required to define how to improve the accuracy of the self-report method because it is the most feasible method in clinical practice.