7 research outputs found
Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries
Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis.
Methods: We identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, hadCD4+ cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4+ cell count and HIV-RNA via inverse probability weighting.
Results: Out of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis.
Conclusion: With the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries
Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis. Methods: We identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, hadCD4+ cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4+ cell count and HIV-RNA via inverse probability weighting. Results: Out of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis. Conclusion: With the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries
Importance of Baseline Prognostic Factors With Increasing Time Since Initiation of Highly Active Antiretroviral Therapy: Collaborative Analysis of Cohorts of HIV-1-Infected Patients
Background: The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods: We analyzed data on 20,379 treatment-naive HIV-1- infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results: Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count 350 cells/μL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions: Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART
Incidence of tuberculosis among HIV-infected patients receiving highly active antiretroviral therapy in Europe and North America
Background. We obtained estimates of the incidence of tuberculosis (TB) among patients receiving HAART and identified determinants of the incidence. Methods. We analyzed the incidence of TB during the first 3 years after initiation of HAART among 17,142 treatment-naive, AIDS- free persons starting HAART who were enrolled in 12 cohorts from Europe and North America. We used univariable and multivariable Poisson regression models to identify factors associated with the incidence. Results. During the first 3 years (36,906 person-years), 173 patients developed TB (incidence, 4.69 cases per 1000 person-years). In multivariable analysis, the incidence rate was lower for men who have sex with men, compared with injection drug users (relative rate, 2.46; 95% confidence interval [CI], 1.51-4.01), heterosexuals (relative rate, 2.42; 95% CI, 1.64-3.59), those with other suspected modes of transmission (relative rate, 1.66; 95% CI, 0.91-3.06), and those with a higher CD4(+) count at the time of HAART initiation (relative rate per log(2) cells/mL, 0.87; 95% CI, 0.84-0.91). During 28,846 person-years of follow-up after the first 6 months of HAART, 88 patients developed TB (incidence, 3.1 cases per 1000 person-years of follow-up). In multivariable analyses, a low baseline CD4(+) count (relative rate per log(2) cells/mL, 0.89; 95% CI, 0.83-0.96), 6-month CD4(+) count (relative rate per log(2) cells/mL, 0.90; 95% CI, 0.81-0.99), and a 6-month HIV RNA level 1400 copies/mL (relative rate, 2.21; 95% CI, 1.33-3.67) were significantly associated with the risk of acquiring TB after 6 months of HAART. Conclusion. The level of immunodeficiency at which HAART is initiated and the response to HAART are important determinants of the risk of TB. However, this risk remains appreciable even among those with a good response to HAART, suggesting that other interventions may be needed to control the TB epidemic in the HIV-infected population
Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?
Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal.
Abstract
Background—The extent to which mortality differs following individual acquired
immunodeficiency syndrome (AIDS)–defining events (ADEs) has not been assessed among
patients initiating combination antiretroviral therapy.
Methods—We analyzed data from 31,620 patients with no prior ADEs who started combination
antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard
ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for
sex, HIV transmission group, number of anti-retroviral drugs initiated, regimen, age, date of
starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation
of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together
to form a “rare ADEs” category.
Results—During a median follow-up period of 43 months (interquartile range, 19–70 months),
2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were
esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and
Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-
Hodgkin’s lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84–22.35) and progressive
multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70–14.92). Three
groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped
confidence intervals: severe (non-Hodgkin’s lymphoma and progressive multifocal
leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55–9.48]), moderate
(cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium
avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76–3.13]), and
mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08–2.00]).
Conclusions—In the combination antiretroviral therapy era, mortality rates subsequent to an
ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in
clinical end point trials, prognostic studies, and patient management
Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal
Abstract
Background—The extent to which mortality differs following individual acquired
immunodeficiency syndrome (AIDS)–defining events (ADEs) has not been assessed among
patients initiating combination antiretroviral therapy.
Methods—We analyzed data from 31,620 patients with no prior ADEs who started combination
antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard
ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for
sex, HIV transmission group, number of anti-retroviral drugs initiated, regimen, age, date of
starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation
of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together
to form a “rare ADEs” category.
Results—During a median follow-up period of 43 months (interquartile range, 19–70 months),
2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were
esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and
Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-
Hodgkin’s lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84–22.35) and progressive
multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70–14.92). Three
groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped
confidence intervals: severe (non-Hodgkin’s lymphoma and progressive multifocal
leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55–9.48]), moderate
(cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium
avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76–3.13]), and
mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08–2.00]).
Conclusions—In the combination antiretroviral therapy era, mortality rates subsequent to an
ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in
clinical end point trials, prognostic studies, and patient management