Impaired CD4 T-Cell Count Response to Combined Antiretroviral Therapy in Antiretroviral-Naive HIV-Infected Patients Presenting With Tuberculosis as AIDS-Defining Condition

Cingolani, Antonella; Lepri, Alessandro Cozzi; Castagna, Antonella; Goletti, Delia; Luca, Andrea De; Scarpellini, Paolo; Fanti, Iuri; Antinori, Andrea; Monforte, Antonella d’Arminio; Girardi, Enrico

doi:10.1093/cid/cir900

Cited by 28 publications

(34 citation statements)

References 36 publications

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“…Our finding that deworming had a significant benefit for females during the first year on ART may be partly explained by the fact that females in our population were younger and less likely to have tuberculosis co-infection, since both age and tuberculosis co-infection were inversely associated with CD4 count in our primary model, and in prior studies [52], [53]. Notably, our models included both age and tuberculosis co-infection, which should account for potential confounding by these factors.…”

Section: Discussionsupporting

confidence: 61%

Empiric Deworming and CD4 Count Recovery in HIV-Infected Ugandans Initiating Antiretroviral Therapy

et al. 2014

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BackgroundThere is conflicting evidence on the immunologic benefit of treating helminth co-infections (“deworming”) in HIV-infected individuals. Several studies have documented reduced viral load and increased CD4 count in antiretroviral therapy (ART) naïve individuals after deworming. However, there are a lack of data on the effect of deworming therapy on CD4 count recovery among HIV-infected persons taking ART.Methodology/Principal FindingsTo estimate the association between empiric deworming therapy and CD4 count after ART initiation, we performed a retrospective observational study among HIV-infected adults on ART at a publicly operated HIV clinic in southwestern Uganda. Subjects were assigned as having received deworming if prescribed an anti-helminthic agent between 7 and 90 days before a CD4 test. To estimate the association between deworming and CD4 count, we fit multivariable regression models and analyzed predictors of CD4 count, using a time-by-interaction term with receipt or non-receipt of deworming. From 1998 to 2009, 5,379 subjects on ART attended 21,933 clinic visits at which a CD4 count was measured. Subjects received deworming prior to 668 (3%) visits. Overall, deworming was not associated with a significant difference in CD4 count in either the first year on ART (β = 42.8; 95% CI, −2.1 to 87.7) or after the first year of ART (β = −9.9; 95% CI, −24.1 to 4.4). However, in a sub-analysis by gender, during the first year of ART deworming was associated with a significantly greater rise in CD4 count (β = 63.0; 95% CI, 6.0 to 120.1) in females.Conclusions/SignificanceEmpiric deworming of HIV-infected individuals on ART conferred no significant generalized benefit on subsequent CD4 count recovery. A significant association was observed exclusively in females and during the initial year on ART. Our findings are consistent with recent studies that failed to demonstrate an immunologic advantage to empirically deworming ART-naïve individuals, but suggest that certain sub-populations may benefit.

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Section: Discussionsupporting

confidence: 61%

Empiric Deworming and CD4 Count Recovery in HIV-Infected Ugandans Initiating Antiretroviral Therapy

et al. 2014

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“…One included abstract [34] was subsequently published as a full article [44]; only data from the full article was included. Three eligible studies were excluded: one because some patients included in the TB treatment-exposed group had completed TB treatment just prior to cART initiation [36], and two because they included some early incident TB cases in their TB treatment-exposed group [20, 31]. Articles reporting on the same study population, but at differing time points following cART initiation, were retained [26, 27, 39].…”

Section: Resultsmentioning

confidence: 99%

The effect of tuberculosis treatment on virologic and CD4+ cell count response to combination antiretroviral therapy

Soeters

Napravnik

Patel³

et al. 2014

Aids

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Objectives To determine the impact of tuberculosis (TB) treatment at the time of combination antiretroviral therapy (cART) initiation on virologic and CD4 count response to cART. Methods Systematic review and meta-analysis of studies reporting HIV RNA and CD4 count response, stratified by TB treatment status at cART initiation. Stratified random-effects and meta-regression analyses were used when possible. Results 25 eligible cohort studies reported data on 49,578 (range 42-15,646) adults, of whom 8,826 (18%) were receiving TB treatment at cART initiation. 17 studies reported virologic response; 21 reported CD4 count response. The summarized random-effects relative risk (RRRE) of virologic suppression in those receiving vs. not receiving TB treatment at different time points following cART initiation was 1.06 (0.86-1.29) at 1-4 months, 0.91 (0.83-1.00) at 6 months, 0.99 (0.94-1.05) at 11-12 months, and 0.99 (0.77-1.28) at 18-48 months. The overall RRRE at 1-48 months was 0.97 (95% CI:0.92-1.03). Available data regarding the effect of TB treatment on virologic failure were heterogeneous and inconclusive (13 estimates). Differences in median CD4 count gain between those receiving vs. not receiving TB treatment ranged from -10 to 60 cells/μL (median 27) by 6 months (7 estimates) and -10 to 29 (median 6) by 11-12 months (5 estimates), though the heterogeneity of the response measures did not support meta-analysis. Conclusions Patients receiving TB treatment at cART initiation experience similar virologic suppression and CD4 count reconstitution as those not receiving TB treatment, reinforcing the need to start cART during TB treatment and allowing more confidence in clinical decision-making.

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“…One reason for this apparent discrepancy may be the different timeframes used for HIV-TB cases. Some have included TB cases diagnosed before starting ART only [8,10,11,13]; others only incident TB cases during early ART [20]; whilst some have combined both [9,12]. Here, when applying various timeframes within the sensitivity analysis, we found there to be little difference within our results.…”

Section: Discussionmentioning

confidence: 71%

“…Previous data on this subject have been conflicting. Most studies have suggested that TB co-infection has no impact [8,10,12,13]; however, recent data from Italy, Uganda and South Africa have described blunted CD4 þ responses in HIV-infected individuals diagnosed with TB prior to, or soon after, initiation of ART [9,11,20]. One reason for this apparent discrepancy may be the different timeframes used for HIV-TB cases.…”

Section: Discussionmentioning

confidence: 99%

“…There are conflicting reports of the impact of TB diagnosis and treatment on CD4 þ cell responses following ART initiation [8][9][10][11][12][13]. Potential mechanisms for impaired CD4 þ responses in the presence of HIV-TB co-infection include the practical difficulties associated with concurrent therapy, as well as possible immunological mechanisms due to increased T-cell activation and apoptosis [14].…”

Section: Introductionmentioning

confidence: 99%

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CD4+ cell count responses to antiretroviral therapy are not impaired in HIV-infected individuals with tuberculosis co-infection

Brown

Zenner

et al. 2015

Aids

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Impaired CD4 T-Cell Count Response to Combined Antiretroviral Therapy in Antiretroviral-Naive HIV-Infected Patients Presenting With Tuberculosis as AIDS-Defining Condition

Cited by 28 publications

References 36 publications

Empiric Deworming and CD4 Count Recovery in HIV-Infected Ugandans Initiating Antiretroviral Therapy

Empiric Deworming and CD4 Count Recovery in HIV-Infected Ugandans Initiating Antiretroviral Therapy

The effect of tuberculosis treatment on virologic and CD4+ cell count response to combination antiretroviral therapy

CD4+ cell count responses to antiretroviral therapy are not impaired in HIV-infected individuals with tuberculosis co-infection

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