Journal Article > ResearchFull Text
N Engl J Med. 2011 October 20; Volume 365 (Issue 16); DOI:10.1056/NEJMoa1013911
Blanc FX, Sok T, Laureillard D, Borand L, Rekacewicz C, et al.
N Engl J Med. 2011 October 20; Volume 365 (Issue 16); DOI:10.1056/NEJMoa1013911
Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy.
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AIDS. 2013 October 23; Volume 27 (Issue 16); DOI:10.1097/01.aids.0000432456.14099.c7
Laureillard D, Marcy O, Madec Y, Chea S, Chan S, et al.
AIDS. 2013 October 23; Volume 27 (Issue 16); DOI:10.1097/01.aids.0000432456.14099.c7
To analyze cases of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in the CAMbodian Early versus Late Introduction of Antiretrovirals (CAMELIA) randomized trial designed to compare early (2 weeks) versus late (8 weeks) antiretroviral therapy (ART) initiation after tuberculosis treatment onset in Cambodia (NCT00226434).
Journal Article > ResearchFull Text
BMC Pediatr. 2007 November 1; Volume 120 (Issue 5); DOI:10.1542/peds.2006-3503
Janssens B, Raleigh B, Soeung S, Akao K, Te V, et al.
BMC Pediatr. 2007 November 1; Volume 120 (Issue 5); DOI:10.1542/peds.2006-3503
OBJECTIVE: Increasing access to highly active antiretroviral therapy to reach all those in need in developing countries (scale up) is slowly expanding to HIV-positive children, but documented experience remains limited. We aimed to describe the clinical, immunologic, and virologic outcomes of pediatric patients with >12 months of highly active antiretroviral therapy in 2 routine programs in Cambodia. METHODS: Between June 2003 and March 2005, 212 children who were younger than 13 years started highly active antiretroviral therapy. Most patients started a standard first-line regimen of lamivudine, stavudine, and nevirapine, using split adult fixed-dosage combinations. CD4 percentage and body weight were monitored routinely. A cross-sectional virologic analysis was conducted in January 2006; genotype resistance testing was performed for patients with a detectable viral load. RESULTS: Mean age of the subjects was 6 years. Median CD4 percentage at baseline was 6. Survival was 92% at 12 months and 91% at 24 months; 13 patients died, and 4 were lost to follow-up. A total of 81% of all patients had an undetectable viral load. Among the patients with a detectable viral load, most mutations were associated with resistance to lamivudine and non-nucleoside reverse-transcriptase inhibitor drugs. Five patients had developed extensive antiretroviral resistance. Being an orphan was found to be a predictor of virologic failure. CONCLUSIONS: This study provides additional evidence of the effectiveness of integrating HIV/AIDS care with highly active antiretroviral therapy for children in a routine setting, with good virologic suppression and immunologic recovery achieved by using split adult fixed-dosage combinations. Viral load monitoring and HIV genotyping are valuable tools for the clinical follow-up of the patients. Orphans should receive careful follow-up and extra support.
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Trop Med Int Health. 2011 February 1; Volume 16 (Issue 2); DOI:10.1111/j.1365-3156.2010.02689.x
Pujades-Rodriguez M, Schramm B, Som L, Nerrienet E, Narom P, et al.
Trop Med Int Health. 2011 February 1; Volume 16 (Issue 2); DOI:10.1111/j.1365-3156.2010.02689.x
Objectives To report immunovirological outcomes and resistance patterns in adults treated with triple combination antiretroviral therapy (cART) for 4 years in an HIV programme of Phnom Penh, Cambodia. Methods It is a longitudinal study and cross-sectional evaluation of adults receiving cART for 4 years. CD4 cell counts and HIV-1 RNA were quantified, and resistance patterns were determined. Drug-related toxicity was assessed by clinicians and through laboratory testing. Results After 4 years of cART start, the cumulative probability of retention in care was 0.80 and survival among patients not lost to follow-up was 0.85. A total of 349 patients (98% of eligible) participated in the cross-sectional evaluation. Ninety per cent were receiving first-line therapy, 29% stavudine- and 58% zidovudine-containing regimens (compared with 94% and 3% at cART initiation). Ninety-three per cent of patients were clinically asymptomatic, and severe lipodystrophy and dyslipidemia were diagnosed in 7.2% and 4.0%, respectively. Good treatment adherence was reported by 83% of patients. Median CD4 T-cell count was 410 cells/μl [IQR 290-511], and 90% of patients had >200 cells/μl. Only 15 (4%) patients had detectable HIV viral load (eight had <200 CD4 cells/μl), five had thymidine analogue mutations, and nine were resistant to two drug classes. In an intention-to-treat analysis, 26.1% (95% CI 22.0-30.5) of patients had failed first-line therapy. Conclusions In this Cambodian cohort of adults who started cART at an advanced stage of HIV disease, we observed good clinical and immunovirological outcomes and self-reported treatment adherence at 4 years of therapy.
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PLOS One. 2014 March 7; Volume 9 (Issue 3); e90350.; DOI:10.1371/journal.pone.0090350
Borand L, Madec Y, Laureillard D, Chou M, Marcy O, et al.
PLOS One. 2014 March 7; Volume 9 (Issue 3); e90350.; DOI:10.1371/journal.pone.0090350
OBJECTIVE
To assess efavirenz plasma concentrations and their association with treatment efficacy and tolerance of efavirenz 600 mg daily in HIV-tuberculosis co-infected patients.
METHODS
HIV-infected adults with CD4+ T cell count ≤ 200/mm(3) received standard 6-month tuberculosis treatment and antiretroviral therapy including a daily-dose of 600 mg of efavirenz, irrespective of their body weight. Mid-dose blood samples were drawn both on tuberculosis treatment (week +2 and week +6 after antiretroviral therapy initiation, and week 22 of follow-up) and off tuberculosis treatment (week 50 of follow-up). Considered therapeutic range was 1,000 to 4,000 ng/mL. Multivariate analysis was performed to evaluate the association between efavirenz concentration below 1,000 ng/mL and virological failure. Linear regression was used to test the association between efavirenz exposure and CD4+ T cell gain. Severe side effects potentially related to efavirenz were described and their association with efavirenz exposure was tested by multivariate analysis.
RESULTS
Efavirenz plasma concentrations were available in 540 patients. Median [interquartile range] efavirenz concentrations were 2,674 ng/mL [1,690-4,533], 2,667 ng/mL [1,753-4,494] and 2,799 ng/mL [1,804-4,744] at week +2, week +6, week 22, respectively, and 2,766 ng/mL [1,941-3,976] at week 50. Efavirenz concentrations were lower at week 50 (off rifampicin) compared to week 22 (on rifampicin) (p<0.001). Late attendance to study visit and low hemoglobinemia were the only factors associated with an increased risk of efavirenz concentration below 1,000 ng/mL. Efavirenz concentration below 1,000 ng/mL was not associated with treatment failure. Efavirenz concentration above 4,000 ng/mL was associated with higher risk of central nervous system side effects (p<0.001) and of hepatotoxicity (p<0.001).
CONCLUSION
Body weight and tuberculosis treatment were not associated with low efavirenz concentrations or treatment failure, supporting the 600 mg daily-dose of efavirenz in HIV-tuberculosis co-infected patients. High efavirenz concentrations were related to a higher risk of central nervous system side effects and hepatotoxicity.
To assess efavirenz plasma concentrations and their association with treatment efficacy and tolerance of efavirenz 600 mg daily in HIV-tuberculosis co-infected patients.
METHODS
HIV-infected adults with CD4+ T cell count ≤ 200/mm(3) received standard 6-month tuberculosis treatment and antiretroviral therapy including a daily-dose of 600 mg of efavirenz, irrespective of their body weight. Mid-dose blood samples were drawn both on tuberculosis treatment (week +2 and week +6 after antiretroviral therapy initiation, and week 22 of follow-up) and off tuberculosis treatment (week 50 of follow-up). Considered therapeutic range was 1,000 to 4,000 ng/mL. Multivariate analysis was performed to evaluate the association between efavirenz concentration below 1,000 ng/mL and virological failure. Linear regression was used to test the association between efavirenz exposure and CD4+ T cell gain. Severe side effects potentially related to efavirenz were described and their association with efavirenz exposure was tested by multivariate analysis.
RESULTS
Efavirenz plasma concentrations were available in 540 patients. Median [interquartile range] efavirenz concentrations were 2,674 ng/mL [1,690-4,533], 2,667 ng/mL [1,753-4,494] and 2,799 ng/mL [1,804-4,744] at week +2, week +6, week 22, respectively, and 2,766 ng/mL [1,941-3,976] at week 50. Efavirenz concentrations were lower at week 50 (off rifampicin) compared to week 22 (on rifampicin) (p<0.001). Late attendance to study visit and low hemoglobinemia were the only factors associated with an increased risk of efavirenz concentration below 1,000 ng/mL. Efavirenz concentration below 1,000 ng/mL was not associated with treatment failure. Efavirenz concentration above 4,000 ng/mL was associated with higher risk of central nervous system side effects (p<0.001) and of hepatotoxicity (p<0.001).
CONCLUSION
Body weight and tuberculosis treatment were not associated with low efavirenz concentrations or treatment failure, supporting the 600 mg daily-dose of efavirenz in HIV-tuberculosis co-infected patients. High efavirenz concentrations were related to a higher risk of central nervous system side effects and hepatotoxicity.
Journal Article > ResearchFull Text
J Int AIDS Soc. 2010 March 21; Volume 13 (Issue 1); DOI:10.1186/1758-2652-13-11
Isaakidis P, Raguenaud ME, Te V, Tray CS, Akao K, et al.
J Int AIDS Soc. 2010 March 21; Volume 13 (Issue 1); DOI:10.1186/1758-2652-13-11
ABSTRACT: BACKGROUND: Long-term outcomes of antiretroviral therapy (ART) in children remain poorly documented in resource-limited settings. The objective of this study was to assess two-and three-year survival, CD4 evolution and virological response among children on ART in a programmatic setting in Cambodia. METHODS: Children treated with first-line ART for at least 24 months were assessed with viral load testing and genotyping. We used Kaplan-Meier analysis for survival and Cox regression to identify risk factors associated with treatment failure. RESULTS: Of 1168 registered HIV-positive children, 670 (57%) started ART between January 2003 and December 2007. Survival probability was 0.93 (95% CI: 0.91-0.95) and 0.91 (95% CI: 0.88-0.93) at 24 and 36 months after ART initiation, respectively. Median CD4 gain for children aged over five years was 704 cells/mm3 at 24 months and 737 at 36 months. Median CD4 percentage gain for children under five years old was 15.2% at 24 months and 15% at 36 months. One hundred and thirty children completed at least 24 months of ART, and 138 completed 36 months: 128 out of 268 (48%) were female. Median age at ART initiation was six years.Overall, 22 children had viral loads of >1000 copies/ml (success ratio = 86% on intention-to-treat-analysis) and 21 of 21 presented mutations conferring resistance mostly to lamivudine and non-nucleoside reverse transcriptase inhibitors. Risk factors for failure after 24 and 36 months were CD4 counts below the threshold for severe immunosupression at those months respectively. Only two out of 22 children with viral loads of >1000 copies/ml met the World Health Organization immunological criteria for failure (sensitivity = 0.1). CONCLUSIONS: Good survival, immunological restoration and viral suppression can be sustained after two to three years of ART among children in resource-constrained settings. Increased access to routine virological measurements is needed for timely diagnosis of treatment failure.
Journal Article > ResearchFull Text
Pathogens. 2023 October 13; Volume 12 (Issue 10); 1241.; DOI:10.3390/pathogens12101241
Pean P, Madec Y, Nerrienet E, Borand L, Laureillard D, et al.
Pathogens. 2023 October 13; Volume 12 (Issue 10); 1241.; DOI:10.3390/pathogens12101241
IRIS is a common complication in HIV-infected patients treated for tuberculosis (TB) and cART. Our aim was to evaluate NK cell reconstitution in HIV-infected patients with TB-IRIS compared to those without IRIS. 147 HIV-infected patients with TB from the CAMELIA trial were enrolled. HIV+TB+ patients were followed for 32 weeks. The NK cell repertoire was assessed in whole blood at different time points. As CAMELIA has two arms (early and late cART initiation), we analysed them separately. At enrolment, individuals had low CD4 cell counts (27 cells/mm3) and high plasma viral loads (5.76 and 5.50 log/mL for IRIS and non-IRIS individuals, respectively). Thirty-seven people developed IRIS (in the early and late arms). In the early and late arms, we observed similar proportions of total NK and NK cell subsets in TB-IRIS and non-IRIS individuals during follow-up, except for the CD56dimCD16pos (both arms) and CD56dimCD16neg (late arm only) subsets, which were higher in TB-IRIS and non-IRIS individuals, respectively, after cART. Regarding the repertoire and markers of NK cells, significant differences (lower expression of NKp30, NKG2A (CD159a), NKG2D (CD314) were observed in TB-IRIS compared to non-IRIS individuals after the start of cART. In the late arm, some changes (increased expression of CD69, NKG2C, CD158i) were observed in TB-IRIS compared to non-IRIS individuals, but only before cART initiation (during TB treatment). KIR expression by NK cells (CD158a and CD158i) was similar in both groups. CD69 expression by NK cells decreased in all groups. Expression of the NCR repertoire (NKp30, NKp44, NKp46) has similar kinetics in TB-IRIS subjects compared to non-IRIS subjects regardless of the arm analysed. NK cell reconstitution appeared to be better in TB-IRIS subjects. Although NK cell reconstitution is impaired in HIV infection after cART, as previously reported, it does not appear to be affected by the development of IRIS in HIV and TB-infected individuals.