Virological failure and development of new resistance mutations according to <scp>CD</scp>4 count at combination antiretroviral therapy initiation

José, Sophie; Quinn, Killian; Dunn, David; Cox, Alison; Sabin, Caroline; Fidler, Sarah

doi:10.1111/hiv.12302

Cited by 6 publications

(3 citation statements)

References 13 publications

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“…However, the proportion with two consecutive viral loads greater than 400 copies/mL or one viral load >10,000 copies/mL in the 12 months pre- versus post-transition did not change (47%, 52%). This is substantially higher than the 10.2% with confirmed viral rebound reported in the broader UK CHIC population of adults starting ART for the first time [32]. Only around half of young adults in our study had a continually suppressed viral load pre- and post-transition, and the viral load trajectories of those who died after transfer to adult care indicated poor ART adherence.…”

Section: Discussioncontrasting

confidence: 61%

Growing up with perinatal HIV: changes in clinical outcomes before and after transfer to adult care in the UK

Judd

Collins

Parrott

et al. 2017

Journal of the International AIDS Society

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Introduction: With improved survival, adolescents with perinatal HIV (PHIV) are transitioning from paediatric to adult care, but there are few published data on clinical outcomes post-transfer. Using linked data from patients in the national UK/Ireland paediatric cohort (CHIPS) and an adult UK cohort of outpatient clinics (UK CHIC), we describe mortality and changes in immunological status post-transfer.Methods: Participants in CHIPS aged ≥13 years by the end of 2013 were linked to the UK CHIC database. Mixed effects models explored changes in CD4 count before and after transfer, including interactions between time and variables where interaction p < 0.05.Results: Of 1,215 paediatric participants aged ≥13 years, 271 (22%) had linked data in UK CHIC. One hundred and forty-six (53%) were female, median age at last visit in paediatric care was 17 [interquartile range, IQR 16,18] years, median duration in paediatric care was 11.8 [6.6,15.5] years, and in adult care was 2.9 [1.5,5.9] years. At last visit in paediatric care, 74% (n = 200) were on ART, increasing to 84% (n = 228, p = 0.001) at last visit in adult care. In the 12 months before leaving paediatric care, 92 (47%) had two consecutive viral loads >400 copies/mL or one viral load >10,000 copies/mL, and likewise 102 (52%) in the 12 months post-transfer (p = 0.79). Seven (3%) people died in adult care. In multivariable analysis, CD4 declined as patients approached transition with a greater decline in those with higher nadir CD4 count (mean rates of decline of 3, 13, 15, 30 cells/mm3 per year for those with nadir CD4 < 100, 100–199, 200–299 and ≥300 cells/mm3, respectively). Post-transition, CD4 continued to decline in some groups (e.g. black males, −20 (−34, −5) cells/mm3 per year post transition, p = 0.007)) while it improved in others. Overall CD4 was higher with later year of birth (14 (7, 21) cells/mm3 per later year). There was no effect of age at transfer or changing hospital at transfer on CD4.Conclusions: Our findings suggest that CD4 in adolescents with perinatal HIV in the UK was declining in the period before transition to adult care, and there was some reversal in this trend post-transfer in some groups. Across the transition period, CD4 was higher in those with later birth years, suggesting improvements in clinical care and/or transition planning over time.

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Section: Discussioncontrasting

confidence: 61%

Growing up with perinatal HIV: changes in clinical outcomes before and after transfer to adult care in the UK

Judd

Collins

Parrott

et al. 2017

Journal of the International AIDS Society

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“…Consistent with previous literature [5,18] viral load before starting treatment was associated with rates of virological failure on treatment, whilst baseline CD4 + cell count more than 200 cells/μl was associated with a lower rate of virological failure on treatment [19]. PLWHIV with the highest baseline CD4 + cell counts (>500 cells/μl) had highest rate of treatment interruption, consistent with previous studies [19,20], which could reflect differences in behaviour and clinical counselling for PLWHIV at lower immediate risk of HIV-related morbidity. Most data in this analysis were from the period before European guidelines recommended starting ART in all PLWHIV irrespective of CD4 + cell count.…”

Section: Discussionsupporting

confidence: 90%

Long-term virological suppression on first-line efavirenz + tenofovir + emtricitabine/lamivudine for HIV-1

Antinori

2019

Aids

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Objectives:Evaluate long-term rates of virological failure and treatment interruption for people living with HIV (PLWHIV) with viral suppression on first-line efavirenz + tenofovir disoproxil fumarate + emtricitabine/lamivudine (EFV + TDF + FTC/3TC), and compare these according to patient characteristics.Methods:PLWHIV enrolled in the Collaboration of Observational HIV Epidemiological Research Europe cohort collaboration, who started first-line EFV + TDF + FTC/3TC at age at least 16 years and had viral suppression (<200 copies/ml) within 9 months were included. Rates of virological failure (≥200 copies/ml) and (complete) treatment interruption were estimated according to years since initial suppression. We used Poisson regression to examine associations of baseline characteristics with rates of virological failure or treatment interruption.Results:Among 19 527 eligible PLWHIV with median (interquartile range) follow-up 3.7 (2.0–5.6) years after initial viral suppression, the estimated rate of the combined incidence of virological failure or treatment interruption fell from 9.0/100 person-years in the first year to less than 4/100 person-years beyond 3 years from suppression; considering only those remaining on EFV + TDF + FTC/3TC, the combined rate dropped from 8.2/100 person-years in the first year to less than 3.5/100 person-years beyond 3 years. PLWHIV with injecting drug-related or heterosexual transmission were at higher risk of virological failure or treatment interruption, as were those of Black ethnicity. PLWHIV aged less than 35 years were at higher risk of virological failure and treatment interruption.Conclusion:PLWHIV starting first-line EFV + TDF + FTC/3TC had low rates of virological failure and treatment interruption up to 10 years from initial suppression. Demographic characteristics can be used to identify subpopulations with higher risks of these outcomes.

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“…In this study, however, the analyses may have been partly confounded by the fact that most of the patients were enrolled on treatment with very low CD4 cell counts. Uy et al [45] and Jose et al [46] in their studies also separately reported that resistance occurs quite regularly in persons who initiate therapy later (with low CD4 count) during infection than in those who initiate ART much earlier. Earlier development of resistance may reduce available therapeutic options later [47].…”

Section: Discussionmentioning

confidence: 98%

Epidemiologic and viral predictors of antiretroviral drug resistance among persons living with HIV in a large treatment program in Nigeria

et al. 2020

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Background: Expanded access to combination antiretroviral therapy (cART) throughout sub-Saharan Africa over the last decade has remarkably improved the prognosis of persons living with HIV (PLWH). However, some PLWH experience virologic rebound after a period of viral suppression, usually followed by selection of drug resistant virus. Determining factors associated with drug resistance can inform patient management and healthcare policies, particularly in resource-limited settings where drug resistance testing is not routine. Methods: A case-control study was conducted using data captured from an electronic medical record in a large treatment program in Nigeria. Cases PLWH receiving cART who developed acquired drug resistance (ADR) and controls were those without ADR between 2004 and 2011. Each case was matched to up to 2 controls by sex, age, and education. Logistic regression was used estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with ADR. Results: We evaluated 159 cases with ADR and 299 controls without ADR. In a multivariate model, factors associated with ADR included older age (OR = 2.35 [age 30-40 years 95% CI 1.29, 4.27], age 41 + years OR = 2.31 [95% CI 1.11, 4.84], compared to age 17-30), higher education level (secondary OR 2.14 [95% CI 1.1.11-4.13]), compared to primary and tertiary), non-adherence to care (OR = 2.48 [95% CI 1.50-4.00]), longer treatment duration (OR = 1.80 [95% CI 1.37-2.35]), lower CD4 count((OR = 0.95 [95% CI 0.95-0.97]) and higher viral load (OR = 1.97 [95% CI 1.44-2.54]). Conclusions: Understanding these predictors may guide programs in developing interventions to identify patients at risk of developing ADR and implementing prevention strategies.

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Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation

Cited by 6 publications

References 13 publications

Growing up with perinatal HIV: changes in clinical outcomes before and after transfer to adult care in the UK

Growing up with perinatal HIV: changes in clinical outcomes before and after transfer to adult care in the UK

Long-term virological suppression on first-line efavirenz + tenofovir + emtricitabine/lamivudine for HIV-1

Epidemiologic and viral predictors of antiretroviral drug resistance among persons living with HIV in a large treatment program in Nigeria

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