Predictors of early mortality and effectiveness of antiretroviral therapy in TB-HIV patients from Brazil

Abstract

Background The implementation of antiretroviral (ARV) therapy caused a significant decrease in HIV-associated mortality worldwide. Nevertheless, mortality is still high among people living with HIV/AIDS and tuberculosis (TB). ARV-naïve HIV patients coinfected with tuberculosis (TB) have more options to treat both diseases concomitantly. Nevertheless, some TB-HIV patients undertaking ARVs (ARV-experienced) are already failing the first line efavirenz-based regimen and seem to display different response to second line ARV therapy and exhibit other predictors of mortality. Methods We performed a retrospective cohort study including 273 patients diagnosed with TB-HIV and treated at a referral center in Rio de Janeiro, Brazil, between 2008 and 2016. Multivariate analysis and Cox regression models were used to evaluate the effectiveness of ARV therapy regimens (viral load [VL] <80 copies from the 4 th to 10 th months after TB therapy introduction) and to identify predictors of early mortality (100 days after TB therapy initiation) considering ARV-naïve and ARV-experienced patients adjusting for sociodemographic, clinical and therapeutic covariates. Findings Survival analysis included 273 patients, out of whom 154 (56.4%) were ARV-naïve and 119 (43.6%) were ARV-experienced. Seven deaths occurred within 6 months of anti-TB treatment, 4 in ARV-naïve and 3 in ARV-experienced patients. Multivariate analysis revealed that in ARV-naïve patients, the chance of death was substantially higher in patients who developed immune reconstitution inflammatory syndrome during the study follow up (HR = 40.6, p<0.01). For ARV-experienced patients, similar analyses failed to identify factors significantly associated with mortality. Variables independently associated with treatment failure for the ARV-naïve group were previous TB (adjusted OR [aOR] = 6.1 p = 0.03) and alcohol abuse (aOR = 3.7 p = 0.01). For ARV-experienced patients, a ritonavir boosted. Protease Inhibitor-based regimen resulted in a 2.6 times higher risk of treatment failure compared to the use of efavirenz based ARV regimens (p = 0.03) and High baseline HIV VL (p = 0.03) were predictors of treatment failure. Conclusions Risk factors for mortality and ARV failure were different for ARV-naïve and ARV-experienced patients. The latter patient group should be targeted for trials with less toxic and rifampicin-compatible drugs to improve TB-HIV treatment outcomes and prevent death.

Clinical and genetic markers associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

“…During follow-up, Group 1 patients were investigated for the identification of IRIS development in both clinical centers. All IRIS cases observed in the study were classified as paradoxical, tuberculosis-associated IRIS, described as an worsening of TB signs and symptoms starting after cART initiation during TB-treatment, mainly presenting enlargement of lymph nodes and inflammatory signs, not explained by any other diseases or by an adverse effect of drug therapy [50,51], as recently detailed/reviewed by our group [52]. In general, the IRIS cases included in the present study were self-resolving, or, if necessary, the patients were treated with corticoidbased therapy, such as Prednisone.…”

Changes in the NK Cell Repertoire Related to Initiation of TB Treatment and Onset of Immune Reconstitution Inflammatory Syndrome in TB/HIV Co-infected Patients in Rio de Janeiro, Brazil—ANRS 12274

“…The primary study population consisted of 33 HIV-infected patients diagnosed with TB (TB/HIV) who started cART 2 weeks (W2) after TB treatment according to the Brazilian Guidelines for HIV/AIDS Treatment and the National Tuberculosis Program (Ministry of Health) at the time of the study (35, 36). Briefly, 4-drugs TB regimen containing rifampicin, isoniazid, pyrazinamide, and ethambutol, followed by the first line HIV treatment with two nucleoside reverse transcriptase inhibitors (NRTI) + non-nucleoside reverse transcriptase inhibitors (NNRTI) (35–37). Tuberculosis diagnosis was made when suggestive clinical symptoms, and radiological findings were present.…”

“…The TB/HIV patients were evaluated at the introduction of anti-TB therapy at the baseline visit (D0), at the initiation of cART (W2) and during the clinical follow-up visits at weeks 6, 10, 14, and 24. Four TB/HIV patients developed paradoxical IRIS defined as a documented clinical worsening of TB signs or symptoms during anti-TB treatment, after cART initiation, not explained by any other diseases or by an adverse effect of drug therapy; lymph node enlargement with inflammatory signs temporally related to cART introduction was considered IRIS in this study (37–39). Each case of IRIS was validated in this study by the members of the clinical coordination team to discard opportunistic disease diagnosis, drug-resistant TB, low adherence, or adverse effects of cART.…”

“…Each case of IRIS was validated in this study by the members of the clinical coordination team to discard opportunistic disease diagnosis, drug-resistant TB, low adherence, or adverse effects of cART. The TB/HIV patients were also analyzed according to their TB clinical presentations as pulmonary (PTB), lymph node TB (LNTB), and disseminated TB (DTB) (when two non-contiguous sites were affected) (37). Moreover, in the context of clinical outcomes, the patient outcomes were evaluated as favorable (TB treatment responders) or unfavorable (death) at the end (usually 6 months) of TB therapy under cART.…”

Impact of Persistent Anemia on Systemic Inflammation and Tuberculosis Outcomes in Persons Living With HIV

“…In a study from Brazil, we have recently described that risk factors for mortality were distinct between HAART-naïve and HAART-experienced PLWH patients coinfected with TB. Indeed, in HAART-naïve patients, but not in those who were already undertaking antiretrovirals, the odds of death were substantially higher in patients who developed immune reconstitution inflammatory syndrome (IRIS) during the study follow up (13). This finding suggests that inflammation during the course of ATT in PLWH is related to unfavorable outcomes.…”