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The effect of injecting drug use history on disease progression and death among HIV-positive individuals initiating combination antiretroviral therapy: collaborative cohort analysis.

ABSTRACT: We examined whether determinants of disease progression and causes of death differ between injecting drug users (IDUs) and non-IDUs who initiate combination antiretroviral therapy (cART).The ART Cohort Collaboration combines data from participating cohort studies on cART-naïve adults from cART initiation. We used Cox models to estimate hazard ratios for death and AIDS among IDUs and non-IDUs. The cumulative incidence of specific causes of death was calculated and compared using methods that allow for competing risks.Data on 6269 IDUs and 37 774 non-IDUs were analysed. Compared with non-IDUs, a lower proportion of IDUs initiated cART with a CD4 cell count <200 cells/?L or had a prior diagnosis of AIDS. Mortality rates were higher in IDUs than in non-IDUs (2.08 vs. 1.04 per 100 person-years, respectively; P<0.001). Lower baseline CD4 cell count, higher baseline HIV viral load, clinical AIDS at baseline, and later year of cART initiation were associated with disease progression in both groups. However, the inverse association of baseline CD4 cell count with AIDS and death appeared stronger in non-IDUs than in IDUs. The risk of death from each specific cause was higher in IDUs than non-IDUs, with particularly marked increases in risk for liver-related deaths, and those from violence and non-AIDS infection.While liver-related deaths and deaths from direct effects of substance abuse appear to explain much of the excess mortality in IDUs, they are at increased risk for many other causes of death, which may relate to suboptimal management of HIV disease in these individuals.

SUBMITTER: Murray M

PROVIDER: S-EPMC4539012 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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The effect of injecting drug use history on disease progression and death among HIV-positive individuals initiating combination antiretroviral therapy: collaborative cohort analysis.

Murray M M Hogg R S RS Lima V D VD May M T MT Moore D M DM Abgrall S S Bruyand M M D'Arminio Monforte A A Tural C C Gill M J MJ Harris R J RJ Reiss P P Justice A A Kirk O O Saag M M Smith C J CJ Weber R R Rockstroh J J Khaykin P P Sterne J A C JA

HIV medicine 20110807 2

<h4>Background</h4>We examined whether determinants of disease progression and causes of death differ between injecting drug users (IDUs) and non-IDUs who initiate combination antiretroviral therapy (cART).<h4>Methods</h4>The ART Cohort Collaboration combines data from participating cohort studies on cART-naïve adults from cART initiation. We used Cox models to estimate hazard ratios for death and AIDS among IDUs and non-IDUs. The cumulative incidence of specific causes of death was calculated a ...[more]

PMID: 21819529

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Project description:ObjectivesWe measured gender differences in "Quality of Care" (QOC) during the first year after initiation of antiretroviral therapy and investigated factors associated with poorer QOC among women.DesignQOC was estimated using the Programmatic Compliance Score (PCS), a validated metric associated with all-cause mortality, among all patients (≥19 years) who initiated ART in British Columbia, Canada (2000-2010).MethodsPCS includes six indicators of non-compliance with treatment initiation guidelines at baseline (not having drug resistance testing before treatment; starting on a non-recommended regimen; starting therapy at CD4<200 cells/mm3) and during first-year follow-up (receiving <3 CD4 tests; receiving <3 viral load tests; not achieving viral suppression within six months). Summary scores range from 0-6; higher scores indicate poorer QOC. Multivariable ordinal logistic regression was used to measure if female gender was an independent predictor of poorer QOC and factors associated with poorer QOC among women.ResultsQOC was determined for 3,642 patients (20% women). At baseline: 42% of women (34% men) did not have resistance testing before treatment; 17% of women (9% men) started on a non-recommended regimen (all p<0.001). At follow-up: 17% of women (11% men) received <3 CD4; 17% of women (11% men) received <3 VL; 50% of women (41% men) did not achieve viral suppression (all p<0.001). Overall, QOC was better among men (mean PSC = 1.54 (SD = 1.30)) compared with women (mean = 1.89 (SD = 1.37); p<0.001). In the multivariable model, female gender (AOR = 1.16 [95% CI: 0.99-1.35]; p = 0.062) remained associated with poorer QOC after covariate adjustment. Among women, those with injection drug use history, of Aboriginal ancestry, from Vancouver Island, and who initiated ART in earlier years were more likely to have poorer QOC.ConclusionsPoorer QOC among women, especially from marginalized communities, demands that barriers undermining women's access to high-quality care be addressed to improve treatment and health for women with HIV.

Project description:ImportanceDespite the introduction of combination antiretroviral therapy (cART), HIV-associated neurocognitive disorders continue to be a problem for treated HIV-positive individuals. The cause of this impairment remains unclear.ObjectiveTo determine if detectable brain changes occur during a 2-year period in HIV-positive individuals who were aviremic and treated with cART.Design, setting, and participantsIn this longitudinal case-control study, participants underwent neuroimaging and neuropsychological assessment approximately 2 years apart. Data were collected from October 26, 2011, to March 1, 2016. Data from 92 HIV-positive individuals were acquired at Washington University in St Louis from ongoing studies conducted in the infectious disease clinic and AIDS Clinical Trial Unit. A total of 55 HIV-negative control participants were recruited from the St Louis community and a research participant registry. A total of 48 HIV-positive individuals who were aviremic and treated with cART and 31 demographically similar HIV-negative controls met the study requirements and were included in the analyses.Main outcomes and measuresBrain volumes were extracted with tensor-based and voxel-based morphometry and cortical modeling. Raw scores from neuropsychological tests quantified cognitive performance. Multivariable mixed-effects models assessed the effect of HIV serostatus on brain volumes and cognitive performance, and determined if HIV serostatus affected how these measures changed over time. With HIV-positive participants, linear regression models tested whether brain volumes and cognitive performance were associated with measures of infection severity and duration of infection.ResultsThe 2 groups were demographically similar (HIV-positive group: 23 women and 25 men; mean [SD] age, 47.7 [13.2] years; mean [SD] educational level, 13.3 [3.4] years; and HIV-negative group, 16 women and 15 men; mean [SD] age, 51.2 [12.9] years; mean [SD] educational level, 14.5 [2.1] years). The HIV-positive participants had poorer neuropsychological test scores compared with controls on the Trail Making Test Part A (5.9 seconds; 95% CI, 1.5-10.3; P = .01), Trail Making Test Part B (27.3 seconds; 95% CI, 15.0-39.6; P < .001), Digit Symbol Substitution Task (-12.5 marks; 95% CI, -18.9 to -6.0; P < .001), Letter-Number Sequencing (-2.5 marks; 95% CI, -3.7 to -1.3; P < .001), Letter Fluency (-6.6 words; 95% CI, -11.5 to -1.6; P = .01), and Hopkins Verbal Learning Test-Revised immediate recall (-2.4 words; 95% CI, -4.4 to -0.4; P = .05), after adjusting for age, sex, and educational level. Only changes in Trail Making Test Part A significantly differed between the groups. Cortical thickness and subcortical volumes were smaller in HIV-positive individuals compared with controls. However, changes in brain volume over time were similar between the groups.Conclusions and relevanceThese findings are consistent with the idea that cognitive and structural brain changes may occur early after seroconversion, and argue that maintaining aviremia with cART can prevent or minimize progressive brain injury.

Project description:BackgroundOptimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined.Methods and findingsA5164 was a randomized strategy trial of "early ART"--given within 14 days of starting acute OI treatment versus "deferred ART"--given after acute OI treatment is completed. Randomization was stratified by presenting OI and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) >or=50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 copies/ml). Secondary endpoints included: AIDS progression/death; plasma HIV RNA and CD4 responses and safety parameters including IRIS. 282 subjects were evaluable; 141 per arm. Entry OIs included Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively. THE DIFFERENCE IN THE PRIMARY ENDPOINT DID NOT REACH STATISTICAL SIGNIFICANCE: AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early ART arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27-0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30-0.92). The early ART had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events.ConclusionsEarly ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications.Trial registrationClinicalTrials.gov NCT00055120.

Dataset Information

The effect of injecting drug use history on disease progression and death among HIV-positive individuals initiating combination antiretroviral therapy: collaborative cohort analysis.

Publications

The effect of injecting drug use history on disease progression and death among HIV-positive individuals initiating combination antiretroviral therapy: collaborative cohort analysis.

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