Journal Article > ResearchFull Text
ACG Case Rep J. 15 September 2023; Volume 25; e39736.; DOI:10.2196/39736
Orel EB, Ciglenecki I, Thiabaud A, Temerev A, Calmy A, et al.
ACG Case Rep J. 15 September 2023; Volume 25; e39736.; DOI:10.2196/39736
BACKGROUND
Literature reviews (LRs) identify, evaluate, and synthesize relevant papers to a particular research question to advance understanding and support decision-making. However, LRs, especially traditional systematic reviews, are slow, resource-intensive, and become outdated quickly.
OBJECTIVE
LiteRev is an advanced and enhanced version of an existing automation tool designed to assist researchers in conducting LRs through the implementation of cutting-edge technologies such as natural language processing and machine learning techniques. In this paper, we present a comprehensive explanation of LiteRev’s capabilities, its methodology, and an evaluation of its accuracy and efficiency to a manual LR, highlighting the benefits of using LiteRev.
METHODS
Based on the user’s query, LiteRev performs an automated search on a wide range of open-access databases and retrieves relevant metadata on the resulting papers, including abstracts or full texts when available. These abstracts (or full texts) are text processed and represented as a term frequency-inverse document frequency matrix. Using dimensionality reduction (pairwise controlled manifold approximation) and clustering (hierarchical density-based spatial clustering of applications with noise) techniques, the corpus is divided into different topics described by a list of the most important keywords. The user can then select one or several topics of interest, enter additional keywords to refine its search, or provide key papers to the research question. Based on these inputs, LiteRev performs a k-nearest neighbor (k-NN) search and suggests a list of potentially interesting papers. By tagging the relevant ones, the user triggers new k-NN searches until no additional paper is suggested for screening. To assess the performance of LiteRev, we ran it in parallel to a manual LR on the burden and care for acute and early HIV infection in sub-Saharan Africa. We assessed the performance of LiteRev using true and false predictive values, recall, and work saved over sampling.
RESULTS
LiteRev extracted, processed, and transformed text into a term frequency-inverse document frequency matrix of 631 unique papers from PubMed. The topic modeling module identified 16 topics and highlighted 2 topics of interest to the research question. Based on 18 key papers, the k-NNs module suggested 193 papers for screening out of 613 papers in total (31.5% of the whole corpus) and correctly identified 64 relevant papers out of the 87 papers found by the manual abstract screening (recall rate of 73.6%). Compared to the manual full text screening, LiteRev identified 42 relevant papers out of the 48 papers found manually (recall rate of 87.5%). This represents a total work saved over sampling of 56%.
CONCLUSIONS
We presented the features and functionalities of LiteRev, an automation tool that uses natural language processing and machine learning methods to streamline and accelerate LRs and support researchers in getting quick and in-depth overviews on any topic of interest.
Literature reviews (LRs) identify, evaluate, and synthesize relevant papers to a particular research question to advance understanding and support decision-making. However, LRs, especially traditional systematic reviews, are slow, resource-intensive, and become outdated quickly.
OBJECTIVE
LiteRev is an advanced and enhanced version of an existing automation tool designed to assist researchers in conducting LRs through the implementation of cutting-edge technologies such as natural language processing and machine learning techniques. In this paper, we present a comprehensive explanation of LiteRev’s capabilities, its methodology, and an evaluation of its accuracy and efficiency to a manual LR, highlighting the benefits of using LiteRev.
METHODS
Based on the user’s query, LiteRev performs an automated search on a wide range of open-access databases and retrieves relevant metadata on the resulting papers, including abstracts or full texts when available. These abstracts (or full texts) are text processed and represented as a term frequency-inverse document frequency matrix. Using dimensionality reduction (pairwise controlled manifold approximation) and clustering (hierarchical density-based spatial clustering of applications with noise) techniques, the corpus is divided into different topics described by a list of the most important keywords. The user can then select one or several topics of interest, enter additional keywords to refine its search, or provide key papers to the research question. Based on these inputs, LiteRev performs a k-nearest neighbor (k-NN) search and suggests a list of potentially interesting papers. By tagging the relevant ones, the user triggers new k-NN searches until no additional paper is suggested for screening. To assess the performance of LiteRev, we ran it in parallel to a manual LR on the burden and care for acute and early HIV infection in sub-Saharan Africa. We assessed the performance of LiteRev using true and false predictive values, recall, and work saved over sampling.
RESULTS
LiteRev extracted, processed, and transformed text into a term frequency-inverse document frequency matrix of 631 unique papers from PubMed. The topic modeling module identified 16 topics and highlighted 2 topics of interest to the research question. Based on 18 key papers, the k-NNs module suggested 193 papers for screening out of 613 papers in total (31.5% of the whole corpus) and correctly identified 64 relevant papers out of the 87 papers found by the manual abstract screening (recall rate of 73.6%). Compared to the manual full text screening, LiteRev identified 42 relevant papers out of the 48 papers found manually (recall rate of 87.5%). This represents a total work saved over sampling of 56%.
CONCLUSIONS
We presented the features and functionalities of LiteRev, an automation tool that uses natural language processing and machine learning methods to streamline and accelerate LRs and support researchers in getting quick and in-depth overviews on any topic of interest.
Conference Material > Abstract
Kerschberger B, Ntshalintshali N, Mafomisa M, Mabhena E, Daka M, et al.
MSF Scientific Day International 2023. 7 June 2023; DOI:10.57740/4e0e-e138
INTRODUCTION
Sexually transmitted infections (STI’s) are a public health threat. Syndromic approaches based on clinical symptoms have been suggested as having poor diagnostic performance, particularly in the type of settings where MSF is operational. We assessed the burden of STI’s and the diagnostic performance of a syndromic approach within an MSF-supported HIV/STI project in Eswatini.
METHODS
We conducted a cross-sectional study, enrolling adults accessing routine HIV testing and antiretroviral care services in six clinics in Shiselweni, from July 2022 to January 2023. HIV testing counselors performed HIV testing and nurses assessed patients for STI’s. Laboratory investigations included antibody-based rapid diagnostic tests (RDT’s) for Treponema pallidum (TP), hepatitis B (HBV) and hepatitis C (HBC). The molecular platform Xpert was used to test urine samples for Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG), vaginal/anal swabs for human papillomavirus (HPV), and plasma for HIV viraemia to test for acute HIV infection (HIV). We calculated the prevalence of STI’s, and assessed diagnostic performance of a syndromic approach to diagnose male urethritis (MUS) and vaginal discharge (VDS) syndromes, versus laboratory-based testing.
ETHICS
This study was approved by the Eswatini Health and Human Research Review Board and by the MSF Ethics Review Board.
RESULTS
Of 1,041 study participants, 682 were women (65.5%), and the median age was 30 (interquartile range, IQR, 24-38) years. Overall, 280 (26.9%) were known HIV-positive and of 755 with unknown HIV status, 30 (4.0%) were newly diagnosed with HIV, of whom seven (23.3%) had AHI. 308 (29.6%) patients had at least one of the following three pathogens identified: NG 121 (11.6%); CT 155 (14.9%); TV 109 (10.5%). MG was detected in 33/330 participants (10.0%). In addition, 105 (10.1%) had antibodies against TP, 49 (4.7%) against HBV, and three (0.3%) against HCV. HPV prevalence was higher in tested women (104/196; 53.1%) versus men (5/27; 18.5%; p=0.001). Prevalence of NG/CT/TP was highest in newly-diagnosed HIV cases (48.2%) versus known HIV-positive cases (26.8%, p=0.019). Based on the syndromic approach, 188/634 (29.7%) had a VDS, and 97/334 (29.0%) a MUS. Diagnostic performance of the syndromic approach was better in men (MUS: sensitivity: 66.7%, specificity 87.5%; positive predictive value, PPV, 70.1%, negative predictive value, NPV, 85.7%), versus women (VDS: sensitivity 35.9%, specificity 72.9%; PPV 35.1%, NPV 73.5%).
CONCLUSION
A high burden of STI’s in Eswatini and poor diagnostic ability of the syndromic approach in this setting, calls for new approaches for STI care in MSF-supported sexual and reproductive health programmes in resource-poor settings.
CONFLICTS OF INTEREST
None declared
Sexually transmitted infections (STI’s) are a public health threat. Syndromic approaches based on clinical symptoms have been suggested as having poor diagnostic performance, particularly in the type of settings where MSF is operational. We assessed the burden of STI’s and the diagnostic performance of a syndromic approach within an MSF-supported HIV/STI project in Eswatini.
METHODS
We conducted a cross-sectional study, enrolling adults accessing routine HIV testing and antiretroviral care services in six clinics in Shiselweni, from July 2022 to January 2023. HIV testing counselors performed HIV testing and nurses assessed patients for STI’s. Laboratory investigations included antibody-based rapid diagnostic tests (RDT’s) for Treponema pallidum (TP), hepatitis B (HBV) and hepatitis C (HBC). The molecular platform Xpert was used to test urine samples for Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG), vaginal/anal swabs for human papillomavirus (HPV), and plasma for HIV viraemia to test for acute HIV infection (HIV). We calculated the prevalence of STI’s, and assessed diagnostic performance of a syndromic approach to diagnose male urethritis (MUS) and vaginal discharge (VDS) syndromes, versus laboratory-based testing.
ETHICS
This study was approved by the Eswatini Health and Human Research Review Board and by the MSF Ethics Review Board.
RESULTS
Of 1,041 study participants, 682 were women (65.5%), and the median age was 30 (interquartile range, IQR, 24-38) years. Overall, 280 (26.9%) were known HIV-positive and of 755 with unknown HIV status, 30 (4.0%) were newly diagnosed with HIV, of whom seven (23.3%) had AHI. 308 (29.6%) patients had at least one of the following three pathogens identified: NG 121 (11.6%); CT 155 (14.9%); TV 109 (10.5%). MG was detected in 33/330 participants (10.0%). In addition, 105 (10.1%) had antibodies against TP, 49 (4.7%) against HBV, and three (0.3%) against HCV. HPV prevalence was higher in tested women (104/196; 53.1%) versus men (5/27; 18.5%; p=0.001). Prevalence of NG/CT/TP was highest in newly-diagnosed HIV cases (48.2%) versus known HIV-positive cases (26.8%, p=0.019). Based on the syndromic approach, 188/634 (29.7%) had a VDS, and 97/334 (29.0%) a MUS. Diagnostic performance of the syndromic approach was better in men (MUS: sensitivity: 66.7%, specificity 87.5%; positive predictive value, PPV, 70.1%, negative predictive value, NPV, 85.7%), versus women (VDS: sensitivity 35.9%, specificity 72.9%; PPV 35.1%, NPV 73.5%).
CONCLUSION
A high burden of STI’s in Eswatini and poor diagnostic ability of the syndromic approach in this setting, calls for new approaches for STI care in MSF-supported sexual and reproductive health programmes in resource-poor settings.
CONFLICTS OF INTEREST
None declared
Journal Article > ResearchFull Text
Lancet Infect Dis. 1 April 2013; 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. 1 April 2013; 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
AIDS. 5 September 2003; Volume 17 (Issue 13); 1995-1997.; DOI: 10.1097/00002030-200309050-00023
Tassie JM, Szumilin E, Calmy A, Goemaere E
AIDS. 5 September 2003; Volume 17 (Issue 13); 1995-1997.; DOI: 10.1097/00002030-200309050-00023
We describe the short-term results of highly active antiretroviral therapy (HAART) in seven projects in low and middle income countries. A total of 743 adults were included, and clinical, immunological and virological responses were analysed. At 6 months, outcomes were similar to those observed in western countries, and the probability of remaining on treatment was 94%. The challenge now is to extend access to HAART to the millions in urgent need.
Journal Article > ReviewAbstract
J Acquir Immune Defic Syndr. 25 January 2019; Volume 80 (Issue 5); DOI:10.1097/QAI.0000000000001957
O'Brien DP, Ford NP, Djirmay AG, Calmy A, Victoria M, et al.
J Acquir Immune Defic Syndr. 25 January 2019; Volume 80 (Issue 5); DOI:10.1097/QAI.0000000000001957
Evidence suggests that there are important interactions between HIV and Female Genital Schistosomiasis (FGS) that may have significant effects on individual and population health. However, the exact way they interact and the health impacts of the interactions are not well understood. In this paper we discuss what is known about the interactions between FGS and HIV, and the potential impact of the interactions. This includes the likelihood that FGS is an important health problem for HIV positive women in schistosoma-endemic areas potentially associated with an increased risk of mortality, cancer and infertility. Additionally, it may be significantly impacting the HIV epidemic in sub-Saharan Africa by making young women more susceptible to HIV. We call for immediate action and argue that research is urgently required to address these knowledge gaps and propose a research agenda to achieve this.
Journal Article > CommentaryFull Text
PLoS Negl Trop Dis. 12 November 2015; Volume 9 (Issue 11); e0004075.; DOI:10.1371/journal.pntd.0004075
O'Brien DP, Ford NP, Vitoria M, Asiedu K, Calmy A, et al.
PLoS Negl Trop Dis. 12 November 2015; Volume 9 (Issue 11); e0004075.; DOI:10.1371/journal.pntd.0004075
Journal Article > ResearchFull Text
AIDS. 1 September 2003; DOI:10.1097/01.aids.0000076325.42412.a1
Tassie JM, Szumilin E, Calmy A, Goemaere E
AIDS. 1 September 2003; DOI:10.1097/01.aids.0000076325.42412.a1
We describe the short-term results of highly active antiretroviral therapy (HAART) in seven projects in low and middle income countries. A total of 743 adults were included, and clinical, immunological and virological responses were analysed. At 6 months, outcomes were similar to those observed in western countries, and the probability of remaining on treatment was 94%. The challenge now is to extend access to HAART to the millions in urgent need.
Journal Article > CommentaryFull Text
BMC Int Health Hum Rights. 31 March 2010; Volume 10 (Issue 1); DOI:10.1186/1472-698X-10-6
Ford NP, Calmy A, Hurst S
BMC Int Health Hum Rights. 31 March 2010; Volume 10 (Issue 1); DOI:10.1186/1472-698X-10-6
ABSTRACT: BACKGROUND: Recent evidence from developed and developing countries shows clear clinical and public health benefit to starting antiretroviral therapy (ART) earlier. While discussions about when to start ART have often focused on the clinical risks and benefits, the main issue is one of fair limit-setting. We applied a human rights framework to assess a policy of early treatment initiation according to the following criteria: public-health purpose; likely effectiveness; specificity; human rights burdens and benefits; potential for less restrictive approaches; and fair administration. DISCUSSION: According to our analysis, a policy of earlier ART initiation would better serve both public health and human rights objectives. We highlight a number of policy approaches that could be taken to help meet this aim, including increased international financial support, alternative models of care, and policies to secure the most affordable sources of appropriate antiretroviral drugs. SUMMARY: Widespread implementation of earlier ART initiation is challenging in resource-limited settings. Nevertheless, rationing of essential medicines is a restriction of human rights, and the principle of least restriction serves to focus attention on alternative measures such as adapting health service models to increase capacity, decreasing costs, and seeking additional international funding. Progressive realisation using well-defined steps will be necessary to allow for a phased implementation as part of a framework of short-term targets towards nationwide policy adoption, and will require international technical and financial support.
Journal Article > ResearchFull Text
Journal of the American Medical Association (JAMA). 21 July 2010; Volume 304 (Issue 3); DOI:10.1001/jama.2010.980
Pujades-Rodríguez M, Balkan S, Arnould L, Brinkhof MW, Calmy A
Journal of the American Medical Association (JAMA). 21 July 2010; Volume 304 (Issue 3); DOI:10.1001/jama.2010.980
CONTEXT
Long-term antiretroviral therapy (ART) use in resource-limited countries leads to increasing numbers of patients with HIV taking second-line therapy. Limited access to further therapeutic options makes essential the evaluation of second-line regimen efficacy in these settings.
OBJECTIVES
To investigate failure rates in patients receiving second-line therapy and factors associated with failure and death.
DESIGN, SETTING, AND PARTICIPANTS
Multicohort study of 632 patients > 14 years old receiving second-line therapy for more than 6 months in 27 ART programs in Africa and Asia between January 2001 and October 2008.
MAIN OUTCOME MEASURES
Clinical, immunological, virological, and immunovirological failure (first diagnosed episode of immunological or virological failure) rates, and mortality after 6 months of second-line therapy use. Sensitivity analyses were performed using alternative CD4 cell count thresholds for immunological and immunovirological definitions of failure and for cohort attrition instead of death.
RESULTS
The 632 patients provided 740.7 person-years of follow-up; 119 (18.8%) met World Health Organization failure criteria after a median 11.9 months following the start of second-line therapy (interquartile range [IQR], 8.7-17.0 months), and 34 (5.4%) died after a median 15.1 months (IQR, 11.9-25.7 months). Failure rates were lower in those who changed 2 nucleoside reverse transcriptase inhibitors (NRTIs) instead of 1 (179.2 vs 251.6 per 1000 person-years; incidence rate ratio [IRR], 0.64; 95% confidence interval [CI], 0.42-0.96), and higher in those with lowest adherence index (383.5 vs 176.0 per 1000 person-years; IRR, 3.14; 95% CI, 1.67-5.90 for < 80% vs > or = 95% [percentage adherent, as represented by percentage of appointments attended with no delay]). Failure rates increased with lower CD4 cell counts when second-line therapy was started, from 156.3 vs 96.2 per 1000 person-years; IRR, 1.59 (95% CI, 0.78-3.25) for 100 to 199/microL to 336.8 per 1000 person-years; IRR, 3.32 (95% CI, 1.81-6.08) for less than 50/microL vs 200/microL or higher; and decreased with time using second-line therapy, from 250.0 vs 123.2 per 1000 person-years; IRR, 1.90 (95% CI, 1.19-3.02) for 6 to 11 months to 212.0 per 1000 person-years; 1.71 (95% CI, 1.01-2.88) for 12 to 17 months vs 18 or more months. Mortality for those taking second-line therapy was lower in women (32.4 vs 68.3 per 1000 person-years; hazard ratio [HR], 0.45; 95% CI, 0.23-0.91); and higher in patients with treatment failure of any type (91.9 vs 28.1 per 1000 person-years; HR, 2.83; 95% CI, 1.38-5.80). Sensitivity analyses showed similar results.
CONCLUSIONS
Among patients in Africa and Asia receiving second-line therapy for HIV, treatment failure was associated with low CD4 cell counts at second-line therapy start, use of suboptimal second-line regimens, and poor adherence. Mortality was associated with diagnosed treatment failure.
Long-term antiretroviral therapy (ART) use in resource-limited countries leads to increasing numbers of patients with HIV taking second-line therapy. Limited access to further therapeutic options makes essential the evaluation of second-line regimen efficacy in these settings.
OBJECTIVES
To investigate failure rates in patients receiving second-line therapy and factors associated with failure and death.
DESIGN, SETTING, AND PARTICIPANTS
Multicohort study of 632 patients > 14 years old receiving second-line therapy for more than 6 months in 27 ART programs in Africa and Asia between January 2001 and October 2008.
MAIN OUTCOME MEASURES
Clinical, immunological, virological, and immunovirological failure (first diagnosed episode of immunological or virological failure) rates, and mortality after 6 months of second-line therapy use. Sensitivity analyses were performed using alternative CD4 cell count thresholds for immunological and immunovirological definitions of failure and for cohort attrition instead of death.
RESULTS
The 632 patients provided 740.7 person-years of follow-up; 119 (18.8%) met World Health Organization failure criteria after a median 11.9 months following the start of second-line therapy (interquartile range [IQR], 8.7-17.0 months), and 34 (5.4%) died after a median 15.1 months (IQR, 11.9-25.7 months). Failure rates were lower in those who changed 2 nucleoside reverse transcriptase inhibitors (NRTIs) instead of 1 (179.2 vs 251.6 per 1000 person-years; incidence rate ratio [IRR], 0.64; 95% confidence interval [CI], 0.42-0.96), and higher in those with lowest adherence index (383.5 vs 176.0 per 1000 person-years; IRR, 3.14; 95% CI, 1.67-5.90 for < 80% vs > or = 95% [percentage adherent, as represented by percentage of appointments attended with no delay]). Failure rates increased with lower CD4 cell counts when second-line therapy was started, from 156.3 vs 96.2 per 1000 person-years; IRR, 1.59 (95% CI, 0.78-3.25) for 100 to 199/microL to 336.8 per 1000 person-years; IRR, 3.32 (95% CI, 1.81-6.08) for less than 50/microL vs 200/microL or higher; and decreased with time using second-line therapy, from 250.0 vs 123.2 per 1000 person-years; IRR, 1.90 (95% CI, 1.19-3.02) for 6 to 11 months to 212.0 per 1000 person-years; 1.71 (95% CI, 1.01-2.88) for 12 to 17 months vs 18 or more months. Mortality for those taking second-line therapy was lower in women (32.4 vs 68.3 per 1000 person-years; hazard ratio [HR], 0.45; 95% CI, 0.23-0.91); and higher in patients with treatment failure of any type (91.9 vs 28.1 per 1000 person-years; HR, 2.83; 95% CI, 1.38-5.80). Sensitivity analyses showed similar results.
CONCLUSIONS
Among patients in Africa and Asia receiving second-line therapy for HIV, treatment failure was associated with low CD4 cell counts at second-line therapy start, use of suboptimal second-line regimens, and poor adherence. Mortality was associated with diagnosed treatment failure.
Journal Article > ResearchFull Text
Lancet HIV. 11 August 2015; Volume 2 (Issue 10); DOI:10.1016/S2352-3018(15)00137-X
Ford NP, Shubber Z, Meintjes GA, Grinsztejn B, Eholie SP, et al.
Lancet HIV. 11 August 2015; Volume 2 (Issue 10); DOI:10.1016/S2352-3018(15)00137-X