Mar, 2012

Short and long term immunological and virological outcome in HIV-infected infants according to the age at antiretroviral treatment initiation. 


Authors: Goetghebuer T, Le Chenadec J, Haelterman E, et al.

Published in: Clinical Infectious Diseases 2012; 54(6): 878-881

Abstract The clinical benefit of antiretroviral therapy in infants is established. In this cohort collaboration, we compare immunological and virological response to treatment started before or after 3 months of age. Early initiation provides a better short-term response, although evolution after 12 months of age is similar in both groups.




Nov, 2011

Early antiretroviral therapy in HIV-1 infected infants, 1996-2008: treatment response and duration of first-line regimens


Authors: The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord.

Published in: AIDS 2011; 25(18): 2279-2287

Background Durable and tolerable first-line antiretroviral therapy (ART) regimens are needed for HIV-infected infants who may need life-long treatment. We investigated virological and immunological response to ART, and predictors of switching and interrupting treatment among infants starting ART in the European Pregnancy and Paediatric HIV Cohort Collaboration.

Methods 9 cohorts from 13 European countries contributed data on HIV-infected infants born 1996-2008 and starting ART before age 12 months. Logistic and linear regression, and competing risks methods were used to assess predictors of virological (viral load <400c/mL) and immunological (change in CD4 Z-score) response, switching to second-line ART and treatment interruptions with viral load <400c/mL.

Findings 437 infants were followed for median 5.9 (interquartile range 2.3-7.6) years after starting ART; 30% had an AIDS diagnosis prior to ART initiation. Virological response improved with calendar year of ART initiation; 53% had suppressed viral load <400c/mL at 12 months in 1996-1999, increasing to 77% in 2004-2008. Virological and immunological responses at 12 months varied by initial ART type (p<0.001 and p=0.03 respectively), with 4-drug NNRTI-based regimens being superior (virological response <400c/mL adjusted OR 3.00, 95%CI 1.24-7.23; mean increase in CD4 Z-score coefficient 0.64, 95%CI 0.10-1.17) to both 3-drug NNRTI-based (reference) and boosted PI regimens which were similar. Rates of switching to second-line ART were lower among children starting 4-drug NNRTI-based and boosted PI-based regimens compared to 3-drug NNRTI regimens (p=0.03). 65% of infants remained on first-line ART without treatment interruption after five years.

Interpretation Effective and prolonged responses to first-line ART can now be achieved in infants starting early ART outside trial settings. Superior responses to 4-drug NNRTI compared





May, 2011

Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multi-cohort study.


Authors: Wittkop L, Günthard HF, de Wolf F, et al. EuroCoord-CHAIN study group.

Published in: Lancet Infectious Diseases 2011; 11(5): 363-71

Background The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration.

Methods HIV-infected patients of any age were included if they started cART (at least three antiretroviral drugs) for the first time after Jan 1, 1998, and were antiretroviral naive and had at least one sample for a genotypic test taken before the start of cART. We used the WHO drug resistance list and the Stanford algorithm to classify patients into three resistance categories: no TDR, at least one mutation and fully-active cART, or at least one mutation and resistant to at least one prescribed drug. Virological failure was defined as time to the first of two consecutive viral load measurements over 500 copies per mL after 6 months of therapy.

Findings Of 10 056 patients from 25 cohorts, 9102 (90·5%) had HIV without TDR, 475 (4·7%) had at least one mutation but received fully-active cART, and 479 (4·8%) had at least one mutation and resistance to at least one drug. Cumulative Kaplan-Meier estimates for virological failure at 12 months were 4·2% (95% CI 3·8–4·7) for patients in the no TDR group, 4·7% (2·9–7·5) for those in the TDR and fully-active cART group, and 15·1% (11·9–19·0) for those in the TDR and resistant group (log-rank p<0·0001). The hazard ratio for the difference in virological failure between patients with TDR and resistance to at least one drug and those without TDR was 3·13 (95% CI 2·33–4·20, p<0·0001). The hazard ratio for the difference between patients with TDR receiving fully-active cART and patients without TDR was 1·47 (95% CI 0·19–2·38, p=0·12). In stratified analysis, the hazard ratio for the risk of virological failure in patients with TDR who received fully-active cART that included a non-nucleoside reverse transcriptase inhibitor (NNRTI) compared with those without TDR was 2·0 (95% CI 0·9–4·7, p=0·093).

Interpretation These findings confirm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients.



May, 2011

Risk of triple-class virological failure in children with HIV: a retrospective cohort study


Authors: Castro H, Judd A, Gibb DM, et al. Pursuing Later Treatment Options II (PLATO II) project team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE).

Published in: Lancet 2011; 377(9777): 1580-1587

Background: In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological suppression can be achieved in most people, even in areas where access is restricted to drugs from these classes. It is unclear whether this is the case for children, the group who will need to maintain viral suppression for longest. We aimed to determine the rate and predictors of triple-class virological failure to the three original drugs classes in children.

Methods: In the Collaboration of Observational HIV Epidemiological Research Europe, the rate of triple-class virological failure was studied in children infected perinatally with HIV who were aged less than 16 years, starting antiretroviral therapy (ART) with three or more drugs, between 1998 and 2008. We used Kaplan-Meier and Cox regression methods to investigate the risk and predictors of triple-class virological failure after ART initiation.

Findings: Of 1007 children followed up for a median of 4·2 (IQR 2·4–6·5) years, 237 (24%) were triple-class exposed and 105 (10%) had triple-class virological failure, of whom 29 never had a viral-load measurement less than 500 copies per mL. Incidence of triple-class virological failure after ART initiation increased with time, and risk by 5 years after ART initiation was 12·0% (95% CI 9·4–14·6). In multivariate analysis, older age at ART initiation was associated with increased risk of failure (p=0·02). Of 686 children starting ART with NRTIs and either a NNRTI or ritonavir-boosted protease inhibitor, the rate of failure was higher than in adults with heterosexually transmitted HIV (hazard ratio 2·2 [95% CI 1·6–3·0, p<0·0001]).

Interpretation: Findings highlight the challenges of attaining long-term viral suppression in children who will be taking life-long ART. Early identification of children not responding to ART, adherence support, particularly for children and adolescents aged 13 years or older starting ART, and ART simplification strategies are all needed to attain and sustain virological suppression.




Mar, 2010

Triple-class virologic failure in HIV-infected patients undergoing antiretroviral therapy for up to 10 years


Authors: Lodwick R, Costagliola D, Reiss P, et al. Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE).

Published in: Archives of Internal Medicine. 2010; 170(5):410-419

Background: Life expectancy in people with HIV is now estimated to approach that in the general population in some successfully treated subgroups. However, to attain these life expectancies, viral suppression must be maintained for decades.

Methods: We studied the rate of triple class virologic failure (TCVF) in patients within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who started antiretroviral therapy (ART) with an NNRTI- or PI/r-containing regimen from 1998 onwards. We also focussed on TCVF in patients who started a PI/r-containing regimen after virologically failing a first-line NNRTI-containing regimen.

Results: Of 45937 patients followed for a median (IQR) 3.0 (1.5-5.0) years, 980 (2.1%) developed TCVF. By 5 and 9 years after starting ART, an estimated 3.4% (95% CI:3.1%-3.6%) and 8.6% (95% CI:7.5%-9.8%) of patients had developed TCVF. The incidence of TCVF rose during the first 3-4 years on ART, but plateaued thereafter. There was no significant difference in the risk of TCVF according to whether the initial regimen was NNRTI- or PI/r-based (p=0.11). By 5 years after starting a PI/r as second-line, 46% of patients had developed TCVF.

Conclusions: The rate of virologic failure of the three original drug classes is low, but not negligible, and does not appear to diminish over time from starting ART. If this trend continues, many patients are likely to need newer drugs to maintain viral suppression. The rate of TCVF from start of a PI/r after NNRTI failure provides a comparator for studies of response to secondline regimens in resource-limited settings.




Mar, 2009

Effect of early antiretroviral therapy on the risk of AIDS/death in HIV infected infants: the European Infant Collaborative Study.


Authors: Goetghebuer T, Haelterman E, Le Chenadec J, et al. for the European infant collaboration group.

Published in: AIDS 2009;23:597-604

Objective: In the absence of treatment, rapid progression to AIDS occurs in approximately 20% of HIV-1-infected infants over the first year of life. The prognosis of these children has considerably improved with highly active antiretroviral therapy. As data from well resourced countries are lacking, the objective of this collaborative study was to evaluate the impact of early treatment in vertically infected infants.

Design: Children born to HIV-infected mothers between 1 September 1996 and 31 December 2004, who were diagnosed with HIV and free of AIDS before 3 months, were eligible. Demographics and pregnancy data, details of antiretroviral therapy, and clinical outcome were collected from 11 European countries.Methods:The risk of AIDS or death, by whether or not an infant started treatment before 3 months of age, was estimated by Kaplan–Meier survival analysis and Cox proportional hazards models.

Results: Among 210 children, 21 developed AIDS and three died. Baseline characteristics of the 124 infants treated before 3 months were similar to those of the 86 infants treated later. The risk of developing AIDS/death at 1 year was 1.6 and 11.7% in the two groups, respectively (P < 0.001). Deferring treatment was associated with increased risk of progression [crude hazard ratio 5.0; 95% confidence interval (CI) 2.0–12.6; P = 0.001] that persisted after adjusting for cohort in multivariate models (adjusted hazard ratio 3.0; 95% CI 1.2–7.9; P = 0.021).

Conclusion: In HIV-1 vertically infected infants, starting antiretroviral therapy before the age of 3 months is associated with a significant reduction in progression to AIDS and death.