8 research outputs found
Dissection aortique anevrismale chez un adulte infecte par le VIH-1 dans le cadre d'un syndrome de reconstitution immune avec tuberculose
We here report the case of a 35-year old man with HIV-1 but with no previous medical-surgical history hospitalized in Abidjan, Cote d'Ivoire, due to fever, cough, dyspnea, chest pain and unfolding of the aortic arch observed on chest x-ray a week after having started antiretroviral therapy (ART). CT angiography of the thoracic aorta showed overall, extended aortic ectasia with mural thrombus. Transesophageal echocardiography objectified type A ascending aortic dissection (Stanford classification). The diagnosis of tuberculosis was confirmed based on Mycobacterium tuberculosis culture isolation. Eight years after, the patient was still alive without surgical treatment and complained of intermittent chest pain. Blood pressure was stable with moderate renal failure. We here report a rare case of aortic aneurism dissection in an adult patient with tuberculosis infected with HIV-1 during immune reconstitution inflammatory syndrome
EBioMedicine
Background High HIV-1 DNA levels in peripheral blood mononuclear cells (PBMC) were associated with a higher risk of severe morbidity and a faster decline in CD4 count in ART-naive patients. We report the association between HIV-1 DNA and mortality in HIV-infected adults in a trial of early ART in West Africa. Methods In the Temprano trial, HIV-infected adults were randomly assigned to start ART immediately or defer ART. After trial termination, HIV-1 DNA was measured in whole blood samples frozen at baseline. We analyzed the association between baseline PBMC HIV-1 DNA and long-term mortality
La chimioprophylaxie antituberculeuse primaire par isoniazide Ă lâĂšre des traitements antirĂ©troviraux
Tuberculosis (TB) has been a worldwide scourge for millennia. It has regressed in the second half of the 20th century before resurging in the 1980s because of the HIV pandemic. Both diseases potentiate each other and form a "cursed duet". In Africa, TB is the leading cause of mortality among HIV-infected adults, regardless of their level of immunity. One of the measures to fight HIV-associated TB is chemoprophylaxis, which consists in treating latent TB infection to prevent the progression to TB disease. The most evaluated chemoprophylaxis, referred to as "Isoniazid Preventive Therapy" (IPT), consists in prescribing 6 to 12 months of isoniazid monotherapy. Since 1993, WHO recommends the prescription of 6 months of IPT in all HIV-infected persons who do not have evidence of active TB. Despite strong scientific evidence to support this recommendation, the use of IPT has remained low. Before our work, there were three reasons for this:(i) people feared that chemoprophylaxis might favor the emergence of resistance to TB drug; (ii) the IPT trials demonstrated the effectiveness of IPT in reducing TB incidence, not in reducing mortality; (iii) most IPT trials took place before the antiretroviral treatment (ART) era, in highly immunocompromised individuals. As ART also reduces the risk of TB by decreasing immunosuppression, some people considered that IPT had become useless. In this work, we first go over the basic knowledge about HIV infection, TB, the combination of the two diseases, and the concept of antituberculous chemoprophylaxis. Then we present the results of the long-term follow-up of the Temprano ANRS 12136 randomized trial, which took place between 2008 and 2015. This trial followed 2056 HIV infected adults in 9 care centers in Abidjan. Participants with high CD4 counts (mean: 477 cells/mm3) were randomized into 4 arms to study two interventions: 6 months of IPT (received vs. not received) and early ART (immediate initiation vs. delayed initiation). Participants were followed for an average of 4.9 years. Eighty nine percent of participants received ART. During follow-up, there were 86 deaths, 34 in patients randomized to IPT (6-year probability: 4.1%, 95% CI 2.9-5.7) and 52 in those randomized to no-IPT (6-year probability: 6.9%, 5.1-9.2). The Hazard ratio of deaths among those randomized to IPT compared to others was 0.63 (95% CI 0.41-0.97). There was no interaction between IPT and early ART, nor between IPT and time. These results were published in The Lancet Global Health. Finally, we discuss these results with those of previous IPT trials, after reviewing all available randomized-controlled evidence on efficacy, safety, efficacy determinants and risks of resistance. We show that the Temprano trial complements and widens the spectrum of evidence accumulated since 1993 and that ART modifies some key parameters of IPT previously thought to be strongly established. Prior to the ART era, evidence suggested that the efficacy of IPT was high in people with positive Tuberculin Skin Test (TST) but very low in those with negative TST; that there was a loss of IPT efficacy over time; and that IPT had no effect on mortality. With ART, IPT appears to be effective regardless of TST results, have prolonged efficacy, and reduce not only TB but also mortality. IPT remains a very topical intervention in the ART era. These results should convince IPT-reluctant countries to implement WHO recommendations.FlĂ©au mondial depuis des millĂ©naires, la tuberculose (TB) a rĂ©gressĂ© dans la deuxiĂšme moitiĂ© du 20Ăšme siĂšcle avant de connaitre une rĂ©surgence Ă partir des annĂ©es 1980 Ă la faveur de la pandĂ©mie du VIH. Les deux maladies se potentialisent mutuellement et forment un « couple infernal ». En Afrique, la TB est la premiĂšre cause de mortalitĂ© des adultes infectĂ©s par le VIH, quel que soit leur niveau dâimmunitĂ©. Une des mesures pour lutter contre la TB associĂ©e au VIH est la chimioprophylaxie, consistant Ă traiter une infection tuberculeuse latente pour prĂ©venir lâĂ©volution vers une TB maladie. La mieux Ă©valuĂ©e, consiste Ă prescrire 6 Ă 12 mois de monothĂ©rapie dâisoniazide (Isoniazid Preventive Therapy, IPT). Depuis 1993, lâOMS recommande la prescription de 6 mois dâIPT chez toutes les personnes infectĂ©es par le VIH sans signe de TB active. MalgrĂ© des preuves scientifiques solides Ă lâappui de cette recommandation, lâutilisation de lâIPT est toujours restĂ©e faible. Avant notre travail, trois raisons expliquaient cette faiblesse : (i) la crainte quâune chimioprophylaxie mal appliquĂ©e ne favorise lâĂ©mergence de rĂ©sistances ; (ii) le fait que les essais avaient dĂ©montrĂ© lâefficacitĂ© de lâIPT pour rĂ©duire lâincidence de TB, pas pour rĂ©duire la mortalitĂ© ; (iii) le fait que les essais dâIPT avaient eu lieu en majoritĂ© avant lâĂšre des antirĂ©troviraux (ARV), chez des personnes trĂšs immunodĂ©primĂ©es. Les ARV permettant Ă©galement de rĂ©duire le risque de TB en faisant rĂ©gresser lâimmunodĂ©pression, certains considĂ©raient que lâIPT Ă©tait devenue inutile. Dans cette thĂšse nous faisons dâabord un rappel des connaissances essentielles sur lâinfection par le VIH, la TB, lâassociation TB/VIH, et le concept de chimioprophylaxie antituberculeuse. Puis nous exposons les rĂ©sultats de lâanalyse du suivi prolongĂ© de lâessai randomisĂ© Temprano ANRS 12136, qui sâest dĂ©roulĂ© entre 2008 et 2015. Cet essai a suivi 2056 adultes infectĂ©s par le VIH dans 9 centres de soins Ă Abidjan. Les participants qui avaient des CD4 Ă©levĂ©s (moyenne 477/mm3) Ă©taient randomisĂ©s en 4 bras pour Ă©tudier deux interventions : 6 mois dâIPT (reçu vs. non reçu) et ARV (dĂ©but immĂ©diat vs. dĂ©but diffĂ©rĂ©). Les participants ont Ă©tĂ© suivis pendant 4,9 ans en moyenne. 89% dâentre eux ont dĂ©butĂ© des ARV. Pendant le suivi, il y a eu 86 dĂ©cĂšs, 34 dans le groupe avec IPT (probabilitĂ© Ă 6 ans : 4,1% ; IC95% 2,9â5,7) et 52 dans le groupe sans IPT (probabilitĂ© Ă 6 ans: 6,9% ; 5,1â9,2). Le Hazard ratio de dĂ©cĂšs dans le groupe avec IPT par rapport Ă lâautre groupe Ă©tait 0,63 (95% CI 0,41-0,97). Il nây avait pas dâinteraction entre IPT et ARV prĂ©coce, ni entre IPT et le temps. Ces rĂ©sultats ont Ă©tĂ© publiĂ©s dans The Lancet Global Health. Enfin nous discutons ces rĂ©sultats avec ceux des essais dâIPT prĂ©cĂ©dents, dans une revue critique de la littĂ©rature analysant les donnĂ©es dâefficacitĂ© et de tolĂ©rance, les dĂ©terminants de lâefficacitĂ©, et les risques de rĂ©sistance. Nous montrons que lâessai Temprano complĂšte et Ă©largit le spectre des connaissances, et que les preuves scientifiques accumulĂ©es depuis 1993 jusquâĂ lâessai Temprano inclus suggĂšrent que les ARV modifient certains paramĂštres de lâIPT quâon pensait solidement Ă©tablis. Avant lâĂšre des ARV on considĂ©rait que lâefficacitĂ© de lâIPT Ă©tait forte chez les personnes avec IDR positive mais trĂšs faible voire inexistante chez les personnes avec IDR nĂ©gative, quâil y avait une perte dâefficacitĂ© de lâIPT au cours du temps et que lâIPT nâavait pas dâeffet sur la mortalitĂ©. Avec les ARV, on voit que lâIPT est efficace quel que soit le rĂ©sultat des tests tuberculiniques, que cette efficacitĂ© est prolongĂ©e, et quâelle se traduit non seulement par une rĂ©duction de la TB mais aussi de la mortalitĂ©. LâIPT reste donc une intervention dâune grande actualitĂ© Ă lâĂšre des ARV. Ces rĂ©sultats devraient convaincre les pays jusque-lĂ rĂ©ticents Ă appliquer les recommandations de lâOMS
Primary Isoniazid Prophylaxis against Tuberculosis in the Era of Antiretroviral Therapy
FlĂ©au mondial depuis des millĂ©naires, la tuberculose (TB) a rĂ©gressĂ© dans la deuxiĂšme moitiĂ© du 20Ăšme siĂšcle avant de connaitre une rĂ©surgence Ă partir des annĂ©es 1980 Ă la faveur de la pandĂ©mie du VIH. Les deux maladies se potentialisent mutuellement et forment un « couple infernal ». En Afrique, la TB est la premiĂšre cause de mortalitĂ© des adultes infectĂ©s par le VIH, quel que soit leur niveau dâimmunitĂ©. Une des mesures pour lutter contre la TB associĂ©e au VIH est la chimioprophylaxie, consistant Ă traiter une infection tuberculeuse latente pour prĂ©venir lâĂ©volution vers une TB maladie. La mieux Ă©valuĂ©e, consiste Ă prescrire 6 Ă 12 mois de monothĂ©rapie dâisoniazide (Isoniazid Preventive Therapy, IPT). Depuis 1993, lâOMS recommande la prescription de 6 mois dâIPT chez toutes les personnes infectĂ©es par le VIH sans signe de TB active. MalgrĂ© des preuves scientifiques solides Ă lâappui de cette recommandation, lâutilisation de lâIPT est toujours restĂ©e faible. Avant notre travail, trois raisons expliquaient cette faiblesse : (i) la crainte quâune chimioprophylaxie mal appliquĂ©e ne favorise lâĂ©mergence de rĂ©sistances ; (ii) le fait que les essais avaient dĂ©montrĂ© lâefficacitĂ© de lâIPT pour rĂ©duire lâincidence de TB, pas pour rĂ©duire la mortalitĂ© ; (iii) le fait que les essais dâIPT avaient eu lieu en majoritĂ© avant lâĂšre des antirĂ©troviraux (ARV), chez des personnes trĂšs immunodĂ©primĂ©es. Les ARV permettant Ă©galement de rĂ©duire le risque de TB en faisant rĂ©gresser lâimmunodĂ©pression, certains considĂ©raient que lâIPT Ă©tait devenue inutile. Dans cette thĂšse nous faisons dâabord un rappel des connaissances essentielles sur lâinfection par le VIH, la TB, lâassociation TB/VIH, et le concept de chimioprophylaxie antituberculeuse. Puis nous exposons les rĂ©sultats de lâanalyse du suivi prolongĂ© de lâessai randomisĂ© Temprano ANRS 12136, qui sâest dĂ©roulĂ© entre 2008 et 2015. Cet essai a suivi 2056 adultes infectĂ©s par le VIH dans 9 centres de soins Ă Abidjan. Les participants qui avaient des CD4 Ă©levĂ©s (moyenne 477/mm3) Ă©taient randomisĂ©s en 4 bras pour Ă©tudier deux interventions : 6 mois dâIPT (reçu vs. non reçu) et ARV (dĂ©but immĂ©diat vs. dĂ©but diffĂ©rĂ©). Les participants ont Ă©tĂ© suivis pendant 4,9 ans en moyenne. 89% dâentre eux ont dĂ©butĂ© des ARV. Pendant le suivi, il y a eu 86 dĂ©cĂšs, 34 dans le groupe avec IPT (probabilitĂ© Ă 6 ans : 4,1% ; IC95% 2,9â5,7) et 52 dans le groupe sans IPT (probabilitĂ© Ă 6 ans: 6,9% ; 5,1â9,2). Le Hazard ratio de dĂ©cĂšs dans le groupe avec IPT par rapport Ă lâautre groupe Ă©tait 0,63 (95% CI 0,41-0,97). Il nây avait pas dâinteraction entre IPT et ARV prĂ©coce, ni entre IPT et le temps. Ces rĂ©sultats ont Ă©tĂ© publiĂ©s dans The Lancet Global Health. Enfin nous discutons ces rĂ©sultats avec ceux des essais dâIPT prĂ©cĂ©dents, dans une revue critique de la littĂ©rature analysant les donnĂ©es dâefficacitĂ© et de tolĂ©rance, les dĂ©terminants de lâefficacitĂ©, et les risques de rĂ©sistance. Nous montrons que lâessai Temprano complĂšte et Ă©largit le spectre des connaissances, et que les preuves scientifiques accumulĂ©es depuis 1993 jusquâĂ lâessai Temprano inclus suggĂšrent que les ARV modifient certains paramĂštres de lâIPT quâon pensait solidement Ă©tablis. Avant lâĂšre des ARV on considĂ©rait que lâefficacitĂ© de lâIPT Ă©tait forte chez les personnes avec IDR positive mais trĂšs faible voire inexistante chez les personnes avec IDR nĂ©gative, quâil y avait une perte dâefficacitĂ© de lâIPT au cours du temps et que lâIPT nâavait pas dâeffet sur la mortalitĂ©. Avec les ARV, on voit que lâIPT est efficace quel que soit le rĂ©sultat des tests tuberculiniques, que cette efficacitĂ© est prolongĂ©e, et quâelle se traduit non seulement par une rĂ©duction de la TB mais aussi de la mortalitĂ©. LâIPT reste donc une intervention dâune grande actualitĂ© Ă lâĂšre des ARV. Ces rĂ©sultats devraient convaincre les pays jusque-lĂ rĂ©ticents Ă appliquer les recommandations de lâOMS.Tuberculosis (TB) has been a worldwide scourge for millennia. It has regressed in the second half of the 20th century before resurging in the 1980s because of the HIV pandemic. Both diseases potentiate each other and form a "cursed duet". In Africa, TB is the leading cause of mortality among HIV-infected adults, regardless of their level of immunity. One of the measures to fight HIV-associated TB is chemoprophylaxis, which consists in treating latent TB infection to prevent the progression to TB disease. The most evaluated chemoprophylaxis, referred to as "Isoniazid Preventive Therapy" (IPT), consists in prescribing 6 to 12 months of isoniazid monotherapy. Since 1993, WHO recommends the prescription of 6 months of IPT in all HIV-infected persons who do not have evidence of active TB. Despite strong scientific evidence to support this recommendation, the use of IPT has remained low. Before our work, there were three reasons for this:(i) people feared that chemoprophylaxis might favor the emergence of resistance to TB drug; (ii) the IPT trials demonstrated the effectiveness of IPT in reducing TB incidence, not in reducing mortality; (iii) most IPT trials took place before the antiretroviral treatment (ART) era, in highly immunocompromised individuals. As ART also reduces the risk of TB by decreasing immunosuppression, some people considered that IPT had become useless. In this work, we first go over the basic knowledge about HIV infection, TB, the combination of the two diseases, and the concept of antituberculous chemoprophylaxis. Then we present the results of the long-term follow-up of the Temprano ANRS 12136 randomized trial, which took place between 2008 and 2015. This trial followed 2056 HIV infected adults in 9 care centers in Abidjan. Participants with high CD4 counts (mean: 477 cells/mm3) were randomized into 4 arms to study two interventions: 6 months of IPT (received vs. not received) and early ART (immediate initiation vs. delayed initiation). Participants were followed for an average of 4.9 years. Eighty nine percent of participants received ART. During follow-up, there were 86 deaths, 34 in patients randomized to IPT (6-year probability: 4.1%, 95% CI 2.9-5.7) and 52 in those randomized to no-IPT (6-year probability: 6.9%, 5.1-9.2). The Hazard ratio of deaths among those randomized to IPT compared to others was 0.63 (95% CI 0.41-0.97). There was no interaction between IPT and early ART, nor between IPT and time. These results were published in The Lancet Global Health. Finally, we discuss these results with those of previous IPT trials, after reviewing all available randomized-controlled evidence on efficacy, safety, efficacy determinants and risks of resistance. We show that the Temprano trial complements and widens the spectrum of evidence accumulated since 1993 and that ART modifies some key parameters of IPT previously thought to be strongly established. Prior to the ART era, evidence suggested that the efficacy of IPT was high in people with positive Tuberculin Skin Test (TST) but very low in those with negative TST; that there was a loss of IPT efficacy over time; and that IPT had no effect on mortality. With ART, IPT appears to be effective regardless of TST results, have prolonged efficacy, and reduce not only TB but also mortality. IPT remains a very topical intervention in the ART era. These results should convince IPT-reluctant countries to implement WHO recommendations
Chimioprophylaxie antituberculeuse primaire Ă l'isoniazide : une stratĂ©gie d'actualitĂ© Ă lâĂšre du tester et traiter ; revue de la littĂ©rature
Position du problĂšme : La tuberculose demeure une menace de santĂ© publique responsable de plus d'un million de dĂ©cĂšs en 2018. La chimioprophylaxie Ă l'isoniazide est une des stratĂ©gies permettant le contrĂŽle de cette maladie. Encore peu prescrite, son intĂ©rĂȘt suscite encore plus de questions Ă lâĂšre du « tester et traiter » concernant les antirĂ©troviraux. L'objectif de cette Ă©tude est donc de rĂ©aliser une revue des essais randomisĂ©s de chimioprophylaxie antituberculeuse primaire Ă l'isoniazide (« thĂ©rapie prĂ©ventive Ă l'isoniazide », TPI), en distinguant les « essais d'efficacitĂ© (EE) » comparant la TPI Ă un placebo ou Ă l'absence de chimioprophylaxie ; et les « essais de rĂ©gime » (ER), comparant la TPI Ă un ou plusieurs autres rĂ©gimes. MĂ©thodes : Recherche bibliographique (mots-clĂ©s sur les bases de donnĂ©es des articles publiĂ©s Medline, Scopus : « tuberculosis », « prophylaxis », « HIV », « randomized controlled trial ») et lecture standardisĂ©e d'articles sĂ©lectionnĂ©s rapportant des rĂ©sultats d'essais randomisĂ©s de TPI chez les personnes infectĂ©es par le VIH. RĂ©sultats : Au total, 18 essais retenus (11 EE et 7 ER), incluant 19 725 participants. Les rĂ©gimes Ă©tudiĂ©s Ă©taient 3H, 6H, 9H, 12H, 36H/2RZ, 3RH, 3RZ, 3RHZ, et 3HP [H : Isoniazide, R : Rifampicine, Z : Pyrazinamide, P : Rifapentine]. Localisation : dix en Afrique, trois Ă HaĂŻti, un en Inde, un aux USA, un aux AmĂ©riques et deux multi continentaux. Dans les EE avec ou sans ARV, la TPI rĂ©duit significativement le risque de tuberculose de 32 % Ă 71 %. Dans les EE avant les ARV, on ne retrouve aucune tendance Ă une rĂ©duction de la mortalitĂ© par la TPI. Dans les EE sous ARV, la TPI rĂ©duit la mortalitĂ©. Dans les ER, on ne trouve aucun argument pour prĂ©fĂ©rer un autre rĂ©gime Ă la TPI. La tolĂ©rance est bonne. La TPI diminue possiblement le risque de sĂ©lection de bacilles multirĂ©sistants, au lieu de l'aggraver, par la baisse du nombre d'Ă©pisodes de tuberculose et donc de l'utilisation des traitements antituberculeux curatifs. Conclusion : Loin d'avoir Ă©tĂ© rendue obsolĂšte par le traitement ARV, la TPI reste une intervention d'actualitĂ©.BACKGROUND: Tuberculosis remains a public health threat responsible as recently as 2018 for more than one million deaths. Chemoprophylaxis with isoniazid is one of the strategies implemented to control the disease. Although it is not yet widely prescribed, its utilization raises additional questions in the "test and treat" era of for anti-retroviral therapy. The objective of this study is to review the different randomized controlled trials of antitubercular Isoniazid Preventive Therapy (IPT). We have distinguished (a) "efficacy trials" (ET) comparing IPT to a placebo or the absence of chemoprophylaxis and (b) "IPT regimen trials" (RT) comparing IPT to one or several other regimens. METHODS: Literature search (keywords from published articles found in the Medline and Scopus data bases: "tuberculosis", "prophylaxis", "HIV", "randomized controlled trial") and standardized reading of selected articles reporting results from randomized trials of IPT in HIV-infected people. RESULTS: Eighteen selected trials (11 ET and 7 RT), including 19,725 participants. The regimens studied were 3H, 6H, 9H, 12H, 12H, 36H/2RZ, 3RH, 3RZ, 3RHZ, and 3HP [H: Isoniazid, R: Rifampicin, Z: Pyrazinamide, P: Rifapentine]. LOCATIONS: Ten in Africa, three in Haiti, one in India, one in the USA, one in the Americas and two multi-continental trials. In ET with or without antiretrovirals (ART), IPT significantly reduces the risk of tuberculosis, by 32 to 71%. In ET prior to ART, IPT does not appear to reduce mortality. In ET in patients receiving ART, on the other hand, IPT reduces mortality. As regards RT, there seems to be no reason to prefer other regimens to IPT. Tolerance is good. Importantly, IPT may reduce (rather than worsen) the risk of multidrug-resistant bacilli selection by decreasing the number of TB episodes and, consequently, the number of curative tuberculosis treatments. CONCLUSION: Far from becoming obsolete due to ARV treatment, IPT has remained a timely and relevant intervention
Association of cellular HIV-1 DNA and virological success of antiretroviral treatment in HIV-infected sub-Saharan African adults
BACKGROUND: HIV-1 DNA persists in infected cells, forming viral reservoirs. Pre-antiretroviral treatment (ART) HIV-1 DNA load was reported to predict ART success in European severely immunocompromised patients. The aim of this study was to determine whether HIV-1 DNA levels are associated with virological success in less severely immunocompromised patients who receive early ART in sub-Saharan Africa. METHODS: The association between pre-ART HIV-1 DNA and the virological response after 30Â months on ART was studied in multivariate logistic regression in patients randomised to immediate ART groups in the Temprano trial, which assessed the benefits of early ART in HIV-infected adults in CĂŽte d'Ivoire. HIV-1 DNA was quantified in peripheral blood mononuclear cell (PBMC) using real-time PCR. RESULTS: HIV-1 DNA levels were measured in 1013 patients. Their medians [IQR] of pre-ART CD4 count, HIV-1 RNA and HIV-1 DNA levels were 465 [379-578]/mm(3), 4.7 [4.0-5.3] log(10) copies/ml and 2.9 [2.5-3.2] log(10) copies/million PBMC, respectively. Pre-ART HIV-1 DNA was significantly correlated with pre-ART HIV-1 RNA (Râ=â0.59, pâ<â0.0001). In multivariate analysis, HIV-1 DNAâ<â3 log(10) copies/million PBMC was significantly associated with virological success at M30 after adjustment for other key variables (ART regimen, IPT, sex, age, WHO clinical stage, CD4 and HIV-1 RNA; aOR 1.57; 95% CI 1.08-2.30; pâ=â0.02). CONCLUSION: Low HIV-1 DNA was statistically associated with virological success in this population of sub-Saharan African adults who started treatment with a median pre-ART CD4 count at 465/mm(3). HIV-1 DNA could become a useful tool for guiding some therapeutic decisions in the test-and-treat era. Trial registration TEMPRANO ANRS 12136 ClinicalTrials.gov, number NCT00495651, date of registration 03/07/2007
Virological failure and drug resistance in West African HIV-infected adults who started ART immediately or deferred ART initiation
BACKGROUND: Asymptomatic HIV-infected people who start ART early may feel less motivated and neglect compliance. This might promote the emergence of resistance. METHODS: In the Temprano trial, ART-naive HIV-infected adults with high CD4 counts were randomly assigned to start ART immediately (immediate group) or defer ART until the WHO criteria were met (deferred group). All participants were monitored for 30âmonths. Those in the deferred group who started ART were monitored for longer, until they had completed 30âmonths on ART. We compared the rate of virological failure and drug resistance between the immediate and deferred groups 30âmonths after ART initiation. RESULTS: Of the 2056 participants in Temprano, 1033 were assigned to start ART immediately and 1023 to defer ART. Of the latter, 488 started ART during trial follow-up. Patients in the deferred group who started ART had a lower median CD4 count (280 versus 465âcells/mm3) and a higher median plasma HIV-1 RNA (5.1 versus 4.7 log10âcopies/mL) at baseline. During follow-up, participants in both groups had similar antiretroviral drug exposure. Thirty months after ART initiation, patients in the deferred group had a higher rate of virological failure (35.3% versus 29.9%, Pâ=â0.04) and a lower genotypic susceptibility score (Pâ=â0.04). CONCLUSIONS: Starting ART early decreases the risk of virological failure and drug resistance in the medium term. This benefit is of particular importance in countries where access to viral load monitoring and the number of antiretroviral drug lines is limited
N Engl J Med
Background In regions with high burdens of tuberculosis and human immunodeficiency virus (HIV), many HIV-infected adults begin antiretroviral therapy (ART) when they are already severely immunocompromised. Mortality after ART initiation is high in these patients, and tuberculosis and invasive bacterial diseases are common causes of death. Methods We conducted a 48-week trial of empirical treatment for tuberculosis as compared with treatment guided by testing in HIV-infected adults who had not previously received ART and had CD4+ T-cell counts below 100 cells per cubic millimeter. Patients recruited in Ivory Coast, Uganda, Cambodia, and Vietnam were randomly assigned in a 1:1 ratio to undergo screening (Xpert MTB/RIF test, urinary lipoarabinomannan test, and chest radiography) to determine whether treatment for tuberculosis should be started or to receive systematic empirical treatment with rifampin, isoniazid, ethambutol, and pyrazinamide daily for 2 months, followed by rifampin and isoniazid daily for 4 months. The primary end point was a composite of death from any cause or invasive bacterial disease within 24 weeks (primary analysis) or within 48 weeks after randomization. Results A total of 522 patients in the systematic-treatment group and 525 in the guided-treatment group were included in the analyses. At week 24, the rate of death from any cause or invasive bacterial disease (calculated as the number of first events per 100 patient-years) was 19.4 with systematic treatment and 20.3 with guided treatment (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 48, the corresponding rates were 12.8 and 13.3 (adjusted hazard ratio, 0.97 [95% CI, 0.67 to 1.40]). At week 24, the probability of tuberculosis was lower with systematic treatment than with guided treatment (3.0% vs. 17.9%; adjusted hazard ratio, 0.15; 95% CI, 0.09 to 0.26), but the probability of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; adjusted hazard ratio 2.57; 95% CI, 1.75 to 3.78). Serious adverse events were more common with systematic treatment. Conclusions Among severely immunosuppressed adults with HIV infection who had not previously received ART, systematic treatment for tuberculosis was not superior to test-guided treatment in reducing the rate of death or invasive bacterial disease over 24 or 48 weeks and was associated with more grade 3 or 4 adverse events