Do Nucleoside Analogues Directly Influence T-Lymphocyte Subset Counts? The Pediatric Model

M, De Martino; Galli, Luisa; Chiarelli, F; Me, Rossi; Vierucci, A

doi:10.1097/00042560-199808010-00013

Cited by 6 publications

(4 citation statements)

References 9 publications

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“…However, of note, only those with high-level (VL) rebound/nonresponse had markedly different immune trajectories. Whilst the specific trajectories varied according to whether T-cell percentages or numbers were considered, as previously reported [9], the inference was consistent, namely that there were many fewer, if any, differences between those suppressed consistently, suppressed with transient blips or with low-level rebound; whereas those with high-level rebound/nonresponse (>5000 copies/ml) were significantly impaired in immune reconstitution and activation.…”

Section: Discussionsupporting

confidence: 71%

Impact of sub-optimal HIV viral control on activated T cells

Arrigoni

Spyer

Hunter

et al. 2023

Aids

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Objective: HIV viral load (VL) monitoring is generally conducted 6–12 monthly in low- and middle-income countries, risking relatively prolonged periods of poor viral control. We explored the effects of different levels of loss of viral control on immune reconstitution and activation. Design: Two hundred and eight participants starting protease inhibitor (PI)-based second-line therapy in the EARNEST trial (ISRCTN37737787) in Uganda and Zimbabwe were enrolled and CD38+/HLA-DR+ immunophenotyping performed (CD8-FITC/CD38-PE/CD3-PerCP/HLA-DR-APC; centrally gated) in real-time at 0, 12, 48, 96 and 144 weeks from randomization. Methods: VL was assayed retrospectively on samples collected every 12–16 weeks and classified as continuous suppression (<40 copies/ml throughout); suppression with transient blips; low-level rebound (two or more consecutive VL >40, <5000 copies/ml); high-level rebound/nonresponse (two or more consecutive VL >5000 copies/ml). Results: Immunophenotype reconstitution varied between that defined by numbers of cells and that defined by cell percentages. Furthermore, VL dynamics were associated with substantial differences in expression of CD4+ and CD8+ cell activation markers, with only individuals with high-level rebound/nonresponse (>5000 copies/ml) experiencing significantly greater activation and impaired reconstitution. There was little difference between participants who suppressed consistently and who exhibited transient blips or even low-level rebound by 144 weeks (P > 0.2 vs. suppressed consistently). Conclusion: Detectable viral load below the threshold at which WHO guidelines recommend that treatment can be maintained without switching (1000 copies/ml) appear to have at most, small effects on reconstitution and activation, for patients taking a PI-based second-line regimen.

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Section: Discussionsupporting

confidence: 71%

Impact of sub-optimal HIV viral control on activated T cells

Arrigoni

Spyer

Hunter

et al. 2023

Aids

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“…20,21 Fourth, ZDV exposure can cause anemia, 4,5 and a direct effect of ZDV on T cells has been postulated. 22,23 Finally, although other unidentified effects could affect the growth and development of ZDV-exposed children, no such effects were seen after 4.5 years of follow-up of children in the ACTG 076 study. 6 Because of concerns raised about the potential effect on mitochondria of prenatal ZDV exposure, 8 we specifically searched for clinical findings that might suggest mitochondrial dysfunction.…”

Section: Discussionmentioning

confidence: 95%

Safety of Late In Utero Exposure to Zidovudine in Infants Born to Human Immunodeficiency Virus-Infected Mothers: Bangkok

Chotpitayasunondh

Vanprapar²,

Simonds³

et al. 2001

Pediatrics

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ABSTRACT. Background. Short-course zidovudine (ZDV) given in the late antenatal period can reduce mother-infant human immunodeficiency virus (HIV) transmission by one half. Because this intervention is being implemented in developing countries, evidence of its safety is needed.Methods. In a randomized, double-blinded, placebocontrolled trial in Bangkok, HIV-infected pregnant women received either ZDV (300 mg twice daily from 36 weeks' gestation until labor, then every 3 hours until delivery) or an identical placebo regimen. Infants were evaluated at birth and at 1, 2, 4, 6, 9, 12, 15, and 18 months of age. Growth, clinical events, and hematologic and immunologic measurements were compared between treatment groups.Results. Of the 395 children born (196 in ZDV group and 199 in placebo group), 330 were uninfected, 55 were infected, and 10 had indeterminate infection status. Overall, 319 children (81%) completed 18 months of follow-up, and 14 (4%) died before 18 months of age. Among uninfected children, the mean hematocrit was lower in the ZDV group at birth (49.1% vs 51.5%) but not at later ages; mean weight, height, head circumference, and CD4 ؉ and CD8 ؉ T lymphocyte counts were similar in both groups at all ages. Five uninfected children in the ZDV group but only one in the placebo group had a febrile convulsion. No other signs suggestive of mitochondrial dysfunction and no tumors were observed. Among infected children, an estimated 62% in the ZDV group and 77% in the placebo group survived free of Centers for Disease Control and Prevention class C disease during the 18-month follow-up.Conclusions. No significant adverse events were associated with short-course ZDV during 18 months of follow-up in this population. Pediatrics 2001;107(1). URL: http://www.pediatrics.org/cgi/content/full/107/1/e5; zidovudine, vertical HIV transmission, children, disease progression, Thailand.

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“…Response to PWM increased from a mean of 27 550 (4268) at day 0 to 36 429 (3368) at day 30 (difference of the mean 8879; 95% CI: 4253-13 505, P=0.002). There was also difference between the SI to PHA and PWM of the patients on antiretroviral therapy at day 30 compared with those in the control group at day 30 (mean [SE]: 43 [8] vs 33 [8], P=0.05 and 34 [6] vs 23 [3], P=0.05, respectively). The SI to PHA and PWM of antiretroviral group returned to normal levels in the day 90 and day 180 determinations.…”

mentioning

confidence: 98%

“…Few studies have analysed the direct role of antiretrovirals on immunological changes, independent of the suppression of viral replication [6][7][8][9][10][11][12]. Levy et al [13] and Milazzo et al [7] hypothesised that zidovudine could promote a redistribution of already formed CD4 T cells, explaining anecdotal increases of CD4 T cells in HIV-1 uninfected individuals taking zidovudine.…”

mentioning

confidence: 99%

Metabolic and Immunological Effects of Antiretroviral Agents in Healthy Individuals Receiving Post-Exposure Prophylaxis

et al. 2002

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We have assessed metabolic and immunological effects of a nelfinavir-containing regimen in healthy HIV-1-uninfected individuals receiving post-exposure prophylaxis. Our data suggest that this regimen is well tolerated and did not modify the lipid or hepatic profiles. This antiretroviral regimen seems to have no effect on lymphocyte T cell subsets, however, it could have an immune-modulator role, inducing an increase in the proliferative responses to mitogens.

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Do Nucleoside Analogues Directly Influence T-Lymphocyte Subset Counts? The Pediatric Model

Cited by 6 publications

References 9 publications

Impact of sub-optimal HIV viral control on activated T cells

Impact of sub-optimal HIV viral control on activated T cells

Safety of Late In Utero Exposure to Zidovudine in Infants Born to Human Immunodeficiency Virus-Infected Mothers: Bangkok

Metabolic and Immunological Effects of Antiretroviral Agents in Healthy Individuals Receiving Post-Exposure Prophylaxis

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