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

Traitement antirétroviral « universel » chez l’adulte infecté par le VIH : Spécificités de l'Afrique sub-Saharienne

The countries of sub-Saharan Africa have seen the number of patients on antiretroviral treatment (ARV) grow rapidly since 2015, when the «universal early treatment »consisting of treating anyone positive for HIV (HIV +) regardless of their CD4count was recommended. The Antiretroviral treatment (ART) improves the survival of HIV +people, reduces the demand for care, increases quality of life, and helps control the epidemic. We demonstrate in this paper that starting ART early also protects against the risk of resistance to treatment.The «Universal early ART »poses two types of questions. First,it is collectively justified, but could be reconsidered individually for subpopulations of HIV+people who are controlling their viraemia without ART. These are the "HIV Controllers". HIV-1 Controllers are well known else where, but poorly documented in Africa. We carried out a prospective estimate and found a prevalence of 1.8% among adults infected with HIV-1 (HIV1+), including 0.7% "Elite Controllers" and 1.1% "Viremic Controllers". The identified "HIV-1 Controllers" had a low level of reservoir markers and inflammatory markers. They maintained a high CD4 count and percentage and had very low morbidity. These people should be better monitored and studied, to determine if any part of them might have more risk than benefit from selling ARV treatment. Some people infected with HIV-2 (HIV2+), might also have an “HIV-2 Controllers” profile, and receive the same attention as HIV1+ “Controllers”. Even though HIV1 + or HIV2 + Controllers represent a small minority of HIV+ people in Africa, it is the responsibility of the health care system to ensure that the strategy of "universalearly ARV treatment" does not put them at risk. Second,if the individual and collective impact of scaling up early ARTis positive on the whole, the challenges remain numerous in terms of screening, access to drugs, adherence, resistanceto drugs, dependence on donors and availability of health care infrastructure and human resources. In many countries, ARTcoverage is insufficient and people are treated too late. When resources are limited, it is advisable to put those who need it most on treatment quickly, while preparing others so that they begin treatment under the best possible conditions of therapeutic education. This reasoning involves an individual approach requiring a good understanding of the factors associated with the progression of the disease. Here we present original data on some of them, including intracellular HIV-1 DNALes pays d’Afrique subsaharienne voient leur nombre de patients sous traitement antirétroviral (ARV) croître de façon rapide depuis 2015, année de recommandation du «traitement précoce universel»consistant à traiter toute personne positive pour le VIH(VIH+) quel que soit son chiffre de CD4. Les ARV améliorent la survie des personnes VIH+, réduisent la demande de soins, augmentent la qualité de vie,facilitent le contrôle de l’épidémie. Nous démontrons dans ce mémoire que leur utilisation précoce protège en outre contre le risque de résistance au traitement.Le « traitement ARV précoce universel» pose deux types de question. Premièrement, il est justifié collectivement, mais pourrait être nuancé individuellement pour des sous-populations de personnes VIH+qui contrôlent leur virémie sans traitement antirétroviral. Il s’agit des "HIV Controllers". Les "HIV-1Controllers"sont bien connus ailleurs, mais mal documentés en Afrique. Nous en avons réalisé une estimation prospective et trouvé une prévalence de 1,8 %parmi les adultes infectés par le VIH, incluant 0,7 % "d'Elite Controllers" et 1,1 % de "Viremic Controllers". Les "HIV-1Controllers" identifiés avaient un faible niveau de marqueurs de réservoir et de marqueurs inflammatoires. Ils maintenaient un nombre et un pourcentage élevés de CD4 et avaient une morbidité très faible. Ces personnes devraient être mieux suivies et étudiées, pour déterminer si une partie d'entre elles pourraient avoir plus de risques que de bénéfices à débuter le traitement ARV. Certaines personnes infectées par le VIH-2 pourraient également avoir un profil «HIV-2Controllers», et faire l'objet de la même attention que les "Controllers" VIH1+. Même si les Controllers" VIH1+ ou VIH2+ représentent une petite minorité des personnes VIH+ en Afrique, il est de la responsabilité du système de soins de s'assurer que la stratégie de "traitement ARV précoce universel" ne leur fait pas courir de risques.Deuxièmement,si l’impact individuel et collectif de cette montée en puissance des traitements est positif dans l’ensemble, les défis demeurent nombreux en termes de dépistage, d’accès aux ARV, d’observance, d’adhésion aux soins, de résistance aux ARV, de dépendance vis-à-vis des bailleurs de fonds et de disponibilité des infrastructures de soins et des ressources humaines. Dans beaucoup de pays, la couverture en ARV demeure insuffisante et les personnes sont traitées trop tard. Lorsque les ressources sont limitées, il est recommandable de mettre sous traitement rapidement ceux qui en ont le plus besoin, tout en préparant les autres pour qu’ils débutent le traitement dans les meilleures conditions d’éducation thérapeutique. Ce raisonnement implique une approche individuelle nécessitant de bien connaitre les facteurs associés à la progression de la maladie. Nous présentons ici des données originales sur certains d'entre eux, incluant le DNA VIH-1 intracellulair

« universal » antiretroviral treatment in HIV-infected adults : Specificities of sub-saharian Africa

Les pays d’Afrique subsaharienne voient leur nombre de patients sous traitement antirétroviral (ARV) croître de façon rapide depuis 2015, année de recommandation du «traitement précoce universel»consistant à traiter toute personne positive pour le VIH(VIH+) quel que soit son chiffre de CD4. Les ARV améliorent la survie des personnes VIH+, réduisent la demande de soins, augmentent la qualité de vie,facilitent le contrôle de l’épidémie. Nous démontrons dans ce mémoire que leur utilisation précoce protège en outre contre le risque de résistance au traitement.Le « traitement ARV précoce universel» pose deux types de question. Premièrement, il est justifié collectivement, mais pourrait être nuancé individuellement pour des sous-populations de personnes VIH+qui contrôlent leur virémie sans traitement antirétroviral. Il s’agit des "HIV Controllers". Les "HIV-1Controllers"sont bien connus ailleurs, mais mal documentés en Afrique. Nous en avons réalisé une estimation prospective et trouvé une prévalence de 1,8 %parmi les adultes infectés par le VIH, incluant 0,7 % "d'Elite Controllers" et 1,1 % de "Viremic Controllers". Les "HIV-1Controllers" identifiés avaient un faible niveau de marqueurs de réservoir et de marqueurs inflammatoires. Ils maintenaient un nombre et un pourcentage élevés de CD4 et avaient une morbidité très faible. Ces personnes devraient être mieux suivies et étudiées, pour déterminer si une partie d'entre elles pourraient avoir plus de risques que de bénéfices à débuter le traitement ARV. Certaines personnes infectées par le VIH-2 pourraient également avoir un profil «HIV-2Controllers», et faire l'objet de la même attention que les "Controllers" VIH1+. Même si les Controllers" VIH1+ ou VIH2+ représentent une petite minorité des personnes VIH+ en Afrique, il est de la responsabilité du système de soins de s'assurer que la stratégie de "traitement ARV précoce universel" ne leur fait pas courir de risques.Deuxièmement,si l’impact individuel et collectif de cette montée en puissance des traitements est positif dans l’ensemble, les défis demeurent nombreux en termes de dépistage, d’accès aux ARV, d’observance, d’adhésion aux soins, de résistance aux ARV, de dépendance vis-à-vis des bailleurs de fonds et de disponibilité des infrastructures de soins et des ressources humaines. Dans beaucoup de pays, la couverture en ARV demeure insuffisante et les personnes sont traitées trop tard. Lorsque les ressources sont limitées, il est recommandable de mettre sous traitement rapidement ceux qui en ont le plus besoin, tout en préparant les autres pour qu’ils débutent le traitement dans les meilleures conditions d’éducation thérapeutique. Ce raisonnement implique une approche individuelle nécessitant de bien connaitre les facteurs associés à la progression de la maladie. Nous présentons ici des données originales sur certains d'entre eux, incluant le DNA VIH-1 intracellulaireThe countries of sub-Saharan Africa have seen the number of patients on antiretroviral treatment (ARV) grow rapidly since 2015, when the «universal early treatment »consisting of treating anyone positive for HIV (HIV +) regardless of their CD4count was recommended. The Antiretroviral treatment (ART) improves the survival of HIV +people, reduces the demand for care, increases quality of life, and helps control the epidemic. We demonstrate in this paper that starting ART early also protects against the risk of resistance to treatment.The «Universal early ART »poses two types of questions. First,it is collectively justified, but could be reconsidered individually for subpopulations of HIV+people who are controlling their viraemia without ART. These are the "HIV Controllers". HIV-1 Controllers are well known else where, but poorly documented in Africa. We carried out a prospective estimate and found a prevalence of 1.8% among adults infected with HIV-1 (HIV1+), including 0.7% "Elite Controllers" and 1.1% "Viremic Controllers". The identified "HIV-1 Controllers" had a low level of reservoir markers and inflammatory markers. They maintained a high CD4 count and percentage and had very low morbidity. These people should be better monitored and studied, to determine if any part of them might have more risk than benefit from selling ARV treatment. Some people infected with HIV-2 (HIV2+), might also have an “HIV-2 Controllers” profile, and receive the same attention as HIV1+ “Controllers”. Even though HIV1 + or HIV2 + Controllers represent a small minority of HIV+ people in Africa, it is the responsibility of the health care system to ensure that the strategy of "universalearly ARV treatment" does not put them at risk. Second,if the individual and collective impact of scaling up early ARTis positive on the whole, the challenges remain numerous in terms of screening, access to drugs, adherence, resistanceto drugs, dependence on donors and availability of health care infrastructure and human resources. In many countries, ARTcoverage is insufficient and people are treated too late. When resources are limited, it is advisable to put those who need it most on treatment quickly, while preparing others so that they begin treatment under the best possible conditions of therapeutic education. This reasoning involves an individual approach requiring a good understanding of the factors associated with the progression of the disease. Here we present original data on some of them, including intracellular HIV-1 DN

Disclosure of HIV positive status : gender differences within the TEMPRANO trial participants, Côte d'Ivoire - ANRS 12239

For people living with HIV, disclosure of HIV status is an important challenge : informed friends or family members can be supportive, or on the contrary can stigmatise the HIV-positive person. We aimed to compare HIV status disclosure among men and women, since gender relationships create different opportunities and difficulties for both sexes. The study was conducted among HIV-positive adults enrolled in the TEMPRANO randomized trial in Côte d'Ivoire, which aims to compare very early antiretroviral treatment versus treatment initiation as per WHO current guidelines. All participants in this trial were asked questions on HIV status disclosure after 24 months of follow- up. Univariate and multivariate analyses were performed to compare disclosure patterns among men and women, disclosure to people living inside and/or outside the household, and in particular to the spouse or regular partner, and to identify the factors associated with disclosure. HIV status disclosure was frequent (more than 80%) among HIV patients, with no difference between men and women (p=0.45). For both, the regular partner was the most frequent confidant. But patterns of disclosure were different : men more frequently disclosed to a regular partner than women (74.1% vs 64.9%, p=0.004), because they were more likely to live with a regular partner (58.6% of men vs 35.8% of women). Men and women living with a regular partner reported similar levels of disclosure to the spouse (82.1% for men and 82.4% for women). Women disclosed more often than men to their children, siblings and mother. For both, the confidants were more often women (sisters, mother) than men (brothers, father). Our study shows that differences in the living conditions of men and women living with HIV and differences in gender roles induce gendered differences in HIV disclosure that should be considered in the care of the patient

Disclosure of HIV positive status : gender differences within the TEMPRANO trial participants, Côte d'Ivoire - ANRS 12239

For people living with HIV, disclosure of HIV status is an important challenge : informed friends or family members can be supportive, or on the contrary can stigmatise the HIV-positive person. We aimed to compare HIV status disclosure among men and women, since gender relationships create different opportunities and difficulties for both sexes. The study was conducted among HIV-positive adults enrolled in the TEMPRANO randomized trial in Côte d'Ivoire, which aims to compare very early antiretroviral treatment versus treatment initiation as per WHO current guidelines. All participants in this trial were asked questions on HIV status disclosure after 24 months of follow- up. Univariate and multivariate analyses were performed to compare disclosure patterns among men and women, disclosure to people living inside and/or outside the household, and in particular to the spouse or regular partner, and to identify the factors associated with disclosure. HIV status disclosure was frequent (more than 80%) among HIV patients, with no difference between men and women (p=0.45). For both, the regular partner was the most frequent confidant. But patterns of disclosure were different : men more frequently disclosed to a regular partner than women (74.1% vs 64.9%, p=0.004), because they were more likely to live with a regular partner (58.6% of men vs 35.8% of women). Men and women living with a regular partner reported similar levels of disclosure to the spouse (82.1% for men and 82.4% for women). Women disclosed more often than men to their children, siblings and mother. For both, the confidants were more often women (sisters, mother) than men (brothers, father). Our study shows that differences in the living conditions of men and women living with HIV and differences in gender roles induce gendered differences in HIV disclosure that should be considered in the care of the patient

Disclosure of HIV positive status : gender differences within the TEMPRANO trial participants, Côte d'Ivoire - ANRS 12239

For people living with HIV, disclosure of HIV status is an important challenge : informed friends or family members can be supportive, or on the contrary can stigmatise the HIV-positive person. We aimed to compare HIV status disclosure among men and women, since gender relationships create different opportunities and difficulties for both sexes. The study was conducted among HIV-positive adults enrolled in the TEMPRANO randomized trial in Côte d'Ivoire, which aims to compare very early antiretroviral treatment versus treatment initiation as per WHO current guidelines. All participants in this trial were asked questions on HIV status disclosure after 24 months of follow- up. Univariate and multivariate analyses were performed to compare disclosure patterns among men and women, disclosure to people living inside and/or outside the household, and in particular to the spouse or regular partner, and to identify the factors associated with disclosure. HIV status disclosure was frequent (more than 80%) among HIV patients, with no difference between men and women (p=0.45). For both, the regular partner was the most frequent confidant. But patterns of disclosure were different : men more frequently disclosed to a regular partner than women (74.1% vs 64.9%, p=0.004), because they were more likely to live with a regular partner (58.6% of men vs 35.8% of women). Men and women living with a regular partner reported similar levels of disclosure to the spouse (82.1% for men and 82.4% for women). Women disclosed more often than men to their children, siblings and mother. For both, the confidants were more often women (sisters, mother) than men (brothers, father). Our study shows that differences in the living conditions of men and women living with HIV and differences in gender roles induce gendered differences in HIV disclosure that should be considered in the care of the patient

Chimioprophylaxie antituberculeuse primaire à l'isoniazide : une stratégie d'actualité à l’ère du tester et traiter ; revue de la littérature

Position du problème : La tuberculose demeure une menace de santé publique responsable de plus d'un million de décès en 2018. La chimioprophylaxie à l'isoniazide est une des stratégies permettant le contrôle de cette maladie. Encore peu prescrite, son intérêt suscite encore plus de questions à l’ère du « tester et traiter » concernant les antirétroviraux. L'objectif de cette étude est donc de réaliser une revue des essais randomisés de chimioprophylaxie antituberculeuse primaire à l'isoniazide (« thérapie préventive à l'isoniazide », TPI), en distinguant les « essais d'efficacité (EE) » comparant la TPI à un placebo ou à l'absence de chimioprophylaxie ; et les « essais de régime » (ER), comparant la TPI à un ou plusieurs autres régimes. Méthodes : Recherche bibliographique (mots-clés sur les bases de données des articles publiés Medline, Scopus : « tuberculosis », « prophylaxis », « HIV », « randomized controlled trial ») et lecture standardisée d'articles sélectionnés rapportant des résultats d'essais randomisés de TPI chez les personnes infectées par le VIH. Résultats : Au total, 18 essais retenus (11 EE et 7 ER), incluant 19 725 participants. Les régimes étudiés étaient 3H, 6H, 9H, 12H, 36H/2RZ, 3RH, 3RZ, 3RHZ, et 3HP [H : Isoniazide, R : Rifampicine, Z : Pyrazinamide, P : Rifapentine]. Localisation : dix en Afrique, trois à Haïti, un en Inde, un aux USA, un aux Amériques et deux multi continentaux. Dans les EE avec ou sans ARV, la TPI réduit significativement le risque de tuberculose de 32 % à 71 %. Dans les EE avant les ARV, on ne retrouve aucune tendance à une réduction de la mortalité par la TPI. Dans les EE sous ARV, la TPI réduit la mortalité. Dans les ER, on ne trouve aucun argument pour préférer un autre régime à la TPI. La tolérance est bonne. La TPI diminue possiblement le risque de sélection de bacilles multirésistants, au lieu de l'aggraver, par la baisse du nombre d'épisodes de tuberculose et donc de l'utilisation des traitements antituberculeux curatifs. Conclusion : Loin d'avoir été rendue obsolète par le traitement ARV, la TPI reste une intervention d'actualité.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

Plasma sVCAM-1, antiretroviral therapy and mortality in HIV-1-infected West African adults

OBJECTIVES: We report the association between pre-antiretroviral therapy (pre-ART) soluble vascular cell adhesion molecule-1 (sVCAM-1) levels and long-term mortality in HIV-infected West African adults participating in a trial of early ART in West Africa (Temprano ANRS 12136 trial). METHODS: The ART-naïve HIV-infected adults were randomly assigned to start ART immediately or defer ART until the WHO criteria were met. Participants who completed the trial follow-up were invited to participate in a post-trial phase (PTP). The PTP end-point was all-cause death. We used multivariable Cox proportional models to analyse the association between baseline sVCAM-1 and all-cause death, adjusting for ART strategy, sex, CD4 count, plasma HIV-1 RNA and peripheral blood mononuclear cell HIV-1 DNA levels. RESULTS: In all, 954 adults (77% women, median CD4 count of 387 cells/μL) were randomly assigned to start ART immediately (n = 477) or to defer initiation of ART (n = 477). They were followed for a median of 5.8 years [interquartile range (IQR): 5.2-6.3]. In multivariable analysis, the risk of death was significantly associated with baseline sVCAM-1 [≥1458 vs. < 1458 ng/mL; adjusted hazard ratio = 2.86, 95% confidence interval (CI): 1.60-5.11]. The 6-year probability of death rates were 14.4% (95%CI: 9.1-22.6) and 9.4% (5.4-16.1) in patients with baseline sVCAM-1 ≥ 1458 ng/mL randomized to deferred and immediate ART, respectively, and 3.8% (2.2-6.5) and 3.5% (1.9-6.3) in patients with baseline sVCAM-1 < 1458 ng/mL randomized to deferred and immediate ART. The median difference between pre-ART and 12-month sVCAM-1 levels in patients randomized to immediate ART was -252 (IQR: -587 to -61). CONCLUSIONS: Pre-ART sVCAM-1 levels were significantly associated with mortality, independently of whether ART was started immediately or deferred, but they significantly decreased after 12 months of ART

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 30 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 Côte 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 (R = 0.59, p < 0.0001). In multivariate analysis, HIV-1 DNA < 3 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; p = 0.02). 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

Incidence and Predictors of Tuberculosis-associated IRIS in People With HIV Treated for Tuberculosis: Findings From Reflate TB2 Randomized Trial

International audienceBACKGROUND: After antiretroviral therapy (ART) initiation, people with HIV (PWH) treated for tuberculosis (TB) may develop TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Integrase inhibitors, by providing a faster HIV-RNA decline than efavirenz, might increase the risk for this complication. We sought to assess incidence and determinants of TB-IRIS in PWH with TB on raltegravir- or efavirenz-based ART. METHODS: We conducted a secondary analysis of the Reflate TB 2 trial, which randomized ART-naive PWH on standard TB treatment, to receive raltegravir- or efavirenz-based ART. The primary objective was to evaluate the incidence of TB-IRIS. Incidence rate ratio comparing TB-IRIS incidence in each arm was calculated. Kaplan-Meier curves were used to compare TB-IRIS-free survival probabilities by ART arm. Cox regression models were fitted to analyze baseline characteristics associated with TB-IRIS. RESULTS: Of 460 trial participants, 453 from Brazil, Côte d'Ivoire, Mozambique, and Vietnam were included in this analysis. Baseline characteristics were median age 35 years (interquartile range [IQR], 29-43), 40% female, 69% pulmonary TB only, median CD4, 102 (IQR, 38-239) cells/mm³, and median HIV RNA, 5.5 (IQR, 5.0-5.8) log copies/mL. Forty-eight participants developed TB-IRIS (incidence rate, 24.7/100 PY), 19 cases in the raltegravir arm and 29 in the efavirenz arm (incidence rate ratio 0.62, 95% confidence interval .35-1.10). Factors associated with TB-IRIS were: CD4 ≤ 100 cells/μL, HIV RNA ≥500 000 copies/mL, and extrapulmonary/disseminated TB. CONCLUSIONS: We did not demonstrate that raltegravir-based ART increased the incidence of TB-IRIS compared with efavirenz-based ART. Low CD4 counts, high HIV RNA, and extrapulmonary/disseminated TB at ART initiation were associated with TB-IRIS