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
BMC Infect Dis. 2011 November 24; Volume 11 (Issue 1); DOI:10.1186/1471-2334-11-327
Heiden D, Saranchuk P
BMC Infect Dis. 2011 November 24; Volume 11 (Issue 1); DOI:10.1186/1471-2334-11-327
AIDS-related CMV retinitis is a common clinical problem in patients with advanced HIV/AIDS in China and Southeast Asia. The disease is causing blindness, and current clinical management, commonly characterized by delayed diagnosis and inadequate treatment, results in poor clinical outcomes: 21% - 36% of eyes with CMV retinitis are already blind at the time the diagnosis is first established by an ophthalmologist. CMV retinitis also identifies a group of patients at extraordinary risk of mortality, and the direct or indirect contribution of extraocular CMV disease to AIDS-related morbidity and mortality is currently unmeasured and clinically often overlooked. The obvious way to improve clinical management of CMV retinitis is to screen all patients with CD4 counts < 100 cells/μL with indirect ophthalmoscopy at the time they first present for care, and to provide systemic treatment with oral valganciclovir when active CMV retinitis is detected. Treatment of opportunistic infections is an integral part of HIV management, and, with appropriate training and support, CMV retinitis screening and treatment can be managed by the HIV clinicians, like all other opportunistic infections. Access to ophthalmologist has been problematic for HIV patients in China, and although non-ophthalmologists can perform screening, sophisticated ophthalmological skills are required for the management of retinal detachment and immune recovery uveitis, the major complications of CMV retinitis. CMV retinitis has been clinically ignored, in part, because of the perceived complexity and expense of treatment, and this obstacle can be removed by making valganciclovir affordable and widely available. Valganciclovir is an essential drug for developing successful programs for management of CMV retinitis in China and throughout SE Asia.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2010 December 1; Volume 14 (Issue 12); 1589-1595.
Minetti A, Camelique O, Hsa Thaw K, Thi SS, Swaddiwudhipong W, et al.
Int J Tuberc Lung Dis. 2010 December 1; Volume 14 (Issue 12); 1589-1595.
SETTING
Although tuberculosis (TB) is a curable disease, it remains a major global health problem and an important cause of morbidity and mortality among vulnerable populations, including refugees and migrants.
OBJECTIVE
To describe results and experiences over 20 years at a TB programme in refugee camps on the Thai-Burmese border in Tak Province, Thailand, and to identify risk factors associated with adverse outcomes (e.g., default, failure, death).
DESIGN
Retrospective review of routine records of 2425 patients admitted for TB treatment in the Mae La TB programme between May 1987 and December 2005.
RESULTS
TB cases notified among refugees decreased over 20 years. Among patients treated with a first-, second- or third-line regimen, 77.5% had a successful outcome, 13.5% defaulted, 7.6% died and 1.3% failed treatment. Multivariate analysis for new cases showed higher likelihood of adverse outcomes for patients who were Burmese migrants or Thai villagers, male, aged >15 years or with smear-negative pulmonary TB.
CONCLUSION
These findings suggest that treatment outcomes depend on the programme's capacity to respond to specific patients' constraints. High-risk groups, such as migrant populations, need a patient-centred approach, and specific, innovative strategies have to be developed based on the needs of the most vulnerable and marginalised populations.
Although tuberculosis (TB) is a curable disease, it remains a major global health problem and an important cause of morbidity and mortality among vulnerable populations, including refugees and migrants.
OBJECTIVE
To describe results and experiences over 20 years at a TB programme in refugee camps on the Thai-Burmese border in Tak Province, Thailand, and to identify risk factors associated with adverse outcomes (e.g., default, failure, death).
DESIGN
Retrospective review of routine records of 2425 patients admitted for TB treatment in the Mae La TB programme between May 1987 and December 2005.
RESULTS
TB cases notified among refugees decreased over 20 years. Among patients treated with a first-, second- or third-line regimen, 77.5% had a successful outcome, 13.5% defaulted, 7.6% died and 1.3% failed treatment. Multivariate analysis for new cases showed higher likelihood of adverse outcomes for patients who were Burmese migrants or Thai villagers, male, aged >15 years or with smear-negative pulmonary TB.
CONCLUSION
These findings suggest that treatment outcomes depend on the programme's capacity to respond to specific patients' constraints. High-risk groups, such as migrant populations, need a patient-centred approach, and specific, innovative strategies have to be developed based on the needs of the most vulnerable and marginalised populations.
Journal Article > LetterFull Text
Trop Med Int Health. 1999 March 1; Volume 4 (Issue 3); 236-238.; DOI:10.1046/j.1365-3156.1999.43384.x
Kumphitak A, Cawthorne P, Lakhonphol S, Kasi-Sedapan S, Sanaeha S, et al.
Trop Med Int Health. 1999 March 1; Volume 4 (Issue 3); 236-238.; DOI:10.1046/j.1365-3156.1999.43384.x
Journal Article > ResearchFull Text
Trop Med Int Health. 2004 November 1; Volume 9 (Issue 11); 1184-1190.; DOI:10.1111/j.1365-3156.2004.01323.x
Smithuis FM, Shahmanesh M, Kyaw MK, Savran O, Lwin S, et al.
Trop Med Int Health. 2004 November 1; Volume 9 (Issue 11); 1184-1190.; DOI:10.1111/j.1365-3156.2004.01323.x
Multi-drug resistant falciparum malaria is widespread in Asia. In Thailand, Cambodia and Vietnam the national protocols have changed largely to artesunate combined treatment regimens but elsewhere in East and South Asia chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) are still widely recommended by national malaria control programmes. In Kachin State, northern Myanmar, an area of low seasonal malaria transmission, the efficacy of CQ (25 mg base/kg) and SP (1.25/25 mg/kg), the nationally recommended treatments at the time, were compared with mefloquine alone (M; 15 mg base/kg) and mefloquine combined with artesunate (MA; 15:4 mg/kg). An open randomized controlled trial enrolled 316 patients with uncomplicated Plasmodium falciparum malaria, stratified prospectively into three age-groups. Early treatment failures (ETF) occurred in 41% (32/78) of CQ treated patients and in 24% of patients treated with SP (18/75). In young children the ETF rates were 87% after CQ and 35% after SP. Four children (two CQ, two SP) developed symptoms of cerebral malaria within 3 days after treatment. By day 42, failure rates (uncorrected for reinfections) had increased to 79% for CQ and 81% for SP. ETF rates were 2.5% after treatment with M and 3.9% after treatment with MA (P > 0.2). Overall uncorrected treatment failure rates at day 42 following M and MA were 23% and 21%, respectively. Chloroquine and SP are completely ineffective for the treatment of falciparum malaria in northern Myanmar. Mefloquine treatment is much more effective, but three day combination regimens with artesunate will be needed for optimum efficacy and protection against resistance.
Journal Article > Meta-AnalysisFull Text
AIDS. 2012 May 15; Volume 26 (Issue 8); DOI:10.1097/QAD.0b013e328351f5b2
Ajose O, Mookerjee S, Mills EJ, Boulle AM, Ford NP
AIDS. 2012 May 15; Volume 26 (Issue 8); DOI:10.1097/QAD.0b013e328351f5b2
A growing proportion of patients on antiretroviral therapy in resource-limited settings have switched to second-line regimens. We carried out a systematic review in order to summarize reported rates and reasons for virological failure among people on second-line therapy in resource-limited settings.
Journal Article > Meta-AnalysisAbstract
J Acquir Immune Defic Syndr. 2013 June 14; Volume 64 (Issue 1); DOI:10.1097/QAI.0b013e31829f05ac
Bonner K, Mezochow A, Roberts TR, Ford NP, Cohn J
J Acquir Immune Defic Syndr. 2013 June 14; Volume 64 (Issue 1); DOI:10.1097/QAI.0b013e31829f05ac
Journal Article > ResearchFull Text
J Clin Microbiol. 2012 May 30; Volume 50 (Issue 8); DOI:10.1128/JCM.01232-12
Schramm B, Hewison CCH, Bonte L, Jones W, Camelique O, et al.
J Clin Microbiol. 2012 May 30; Volume 50 (Issue 8); DOI:10.1128/JCM.01232-12
Simple tuberculosis (TB) treatment monitoring tools are needed. We assessed the performance of fluorescein-diacetate (FDA) smear microscopy for detection of viable Mycobacterium tuberculosis in sputum specimens (n = 288) of TB cases under treatment compared to culture (17.4% culture positivity). FDA sensitivity was moderate (83.7% [95% confidence interval {CI}, 70.3 to 92.6]), and specificity was low (66.1% [59.5 to 72.2]). The good negative predictive value (94.8% [90.1 to 97.8]) and negative likelihood ratio (0.2) suggest using this method to rule out treatment failure in settings without access to culture.
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 2007 September 1; Volume 77 (Issue 3); 447-450.
Mytton OT, Ashley EA, Peto L, Price RN, La Y, et al.
Am J Trop Med Hyg. 2007 September 1; Volume 77 (Issue 3); 447-450.
Dihydroartemisinin-piperaquine (DP) could become a leading fixed combination malaria treatment worldwide. Although there is accumulating evidence of efficacy and safety from clinical trials, data on cardiotoxicity are limited. In two randomized controlled trials in Thailand, 56 patients had ECGs performed before treatment, 4 hours after the first dose, and 4 hours after the last dose. The mean (95% CI) changes in QTc interval (Bazett's correction) were 2 (-6 to 9) ms and 14 (7 to 21) ms, respectively. These small changes on the third day of treatment are similar to those observed elsewhere in the convalescent phase following antimalarial treatment with drugs known to have no cardiac effects and are therefore likely to result from recovery from acute malaria and not the treatment given. At therapeutic doses, DP does not have clinically significant effects on the electrocardiogram.
Journal Article > ResearchFull Text
J Infect Dis. 2007 April 1; Volume 195 (Issue 7); DOI:10.1086/512241
Imwong M, Snounou G, Pukrittayakamee S, Tanomsing N, Kim JH, et al.
J Infect Dis. 2007 April 1; Volume 195 (Issue 7); DOI:10.1086/512241
BACKGROUND: Relapses originating from hypnozoites are characteristic of Plasmodium vivax infections. Thus, reappearance of parasitemia after treatment can result from relapse, recrudescence, or reinfection. It has been assumed that parasites causing relapse would be a subset of the parasites that caused the primary infection. METHODS: Paired samples were collected before initiation of antimalarial treatment and at recurrence of parasitemia from 149 patients with vivax malaria in Thailand (n=36), where reinfection could be excluded, and during field studies in Myanmar (n=75) and India (n=38). RESULTS: Combined genetic data from 2 genotyping approaches showed that novel P. vivax populations were present in the majority of patients with recurrent infection (107 [72%] of 149 patients overall [78% of patients in Thailand, 75% of patients in Myanmar {Burma}, and 63% of patients in India]). In 61% of the Thai and Burmese patients and in 55% of the Indian patients, the recurrent infections contained none of the parasite genotypes that caused the acute infection. CONCLUSIONS: The P. vivax populations emerging from hypnozoites commonly differ from the populations that caused the acute episode. Activation of heterologous hypnozoite populations is the most common cause of first relapse in patients with vivax malaria.