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January 2012


No evidence of clinical benefit for patients starting treatment with a healthy immune system
 
A paper published by the CASCADE Collaboration in EuroCoord has found no evidence of clinical benefit for patients starting HIV treatment at higher CD4 cell counts of between 500-799 cells/mm³.
 
The introduction of highly active antiretroviral therapy (HAART) in 1996 greatly improved the survival rates of HIV positive people. Although the benefits of treatment are evident, a central unresolved issue is when treatment should be initiated.
 
HIV positive people are advised to start treatment when important cells in their immune system, called CD4 cells, fall below a certain threshold.
 
Current guidelines in the United States recommend that patients start treatment when their CD4 count is between 350 to 500 CD4 cells/mm³ while the threshold for treatment initiation in Europe generally remains at 350 CD4 cells/mm³.
 
This analysis included a total of 9,455 eligible patients from CASCADE who had not yet started treatment, had not developed AIDS, and had CD4 counts of less than 800 cells/mm³.
 
The authors used a novel technique where a series of sequential subcohorts of patients were created. Each month between January 1996 and May 2009 was considered the starting point for a subcohort, with patients who initiated treatment at a number of CD4 strata during the month being compared with those who did not. The results from the resulting 161 subcohorts were then pooled and analysed.    
 
The results confirmed the clinical benefit of starting treatment with CD4 cell counts of between 200-349 cells/mm³, with an estimate of a 25% reduction in the risk of AIDS or death.
 
Although the authors also found a benefit for patients initiating treatment at CD4 cell counts of 350-499 cells/mm³, this was only evident beyond 2 years. There was no clinical benefit for patients beginning treatment at higher CD4 cell counts of between 500-799 cells/mm³.
 
Therefore, the authors suggest that “patients need to consider the long-term course of treatment, including the risk of adverse effects of HAART during an extended period.” 
 
 
Writing Committee for the CASCADE Collaboration. Timing of HAART initiation and clinical outcomes in HIV-1 seroconverters. Arch Intern Med 2011;171:1560-9. [PubMed]

Read more about EuroCoord
 


November 2011

Young Investigator Awards for CASCADE-EuroCoord researchers   

The following two abstracts have been accepted as posters to the 19th Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, March 2012:

Proportion of HIV elite controllers and loss of elite status according to two commonly used definitions - Ashley Olson, Laurence Meyer, Maria Prins, Rodolphe Thiebaut, Marguerite Guiguet, Marie-Laure Chaix, Pauli Amornkul, Abdel Babiker and Kholoud Porter for CASCADE Collaboration in EuroCoord

Identification of severe primary HIV infection through clinical, immunological and virological definitions - Sara Lodi, Martin Fisher, Andrew Phillips, Andrea De Luca, Jade Ghosn, Ruslan Malyuta, Robert Zangerle, Santiago Moreno, Kholoud Porter for CASCADE Collaboration in EuroCoord

Both Ashley and Sara have received the CROI Young Investigator Award.


A study by the CASCADE Collaboration in EuroCoord has estimated that there will be a substantial increase in the number of HIV positive people who will require treatment within the first 5 years after becoming infected, following changes in treatment guidelines.

HIV positive people start treatment when important cells in their immune system, called CD4 cells, fall below a certain threshold.

Updates to the International AIDS Society-United States (IAS-US), Department of Health and Human Services (DHHS), and World Health Organisation guidelines have raised the thresholds for treatment initiation from 350 to 500 CD4 cells/mm³ in the United States and from 200 to 350 CD4 cells/mm³ in mid- and low-income countries. The threshold for treatment initiation remains at 350 cells/mm³ in Europe.

To assess the likely impact of these changes on the number of HIV positive people in need of treatment, the authors used CASCADE data from 18,495 people with well-estimated dates of HIV infection.

Restricting the analyses to adults (above 16 years), the authors then predicted the time between infection and CD4 cell counts of <200, <350, and <500 cells/mm³ being reached, as well as the proportions reaching these thresholds at 1, 2, and 5 years after infection.

The authors estimated that CD4 cell counts <500, <350, and <200 cells/mm³ are reached, on average, at approximately 1, 4, and 8 years after infection, respectively.

They also estimated that, of 100 newly infected people, 48, on average, would require treatment within 1 year of infection if they were to follow guidelines indicating treatment initiation at 500 cells/mm³. This is compared with 27 and 9 individuals requiring treatment if they were to follow guidelines advising them to start at 350 and 200 cells/mm³, respectively.

These results provide support for public health campaigns to encourage early testing and diagnosis particularly in targeted populations at an increased risk of HIV infection, to enable those who are HIV positive to initiate therapy at the optimum time.

However, they also emphasise the greater number of HIV positive people who will need to be treated. The lead author, Sara Lodi, concludes:

 “Given the substantial increase in the number of individuals eligible for treatment as a result of the latest changes in guidelines, it is crucial that the choice of the CD4 cell count threshold for cART initiation is supported by evidence of benefit from randomised controlled trials and appropriate cost-effectiveness considerations.”

Lodi S, Phillips A, Touloumi G, Geskus R, Meyer L, Thiébaut R, Pantazis N, del Amo J, Johnson A M, Babiker A, Porter K on behalf of the CASCADE Collaboration in EuroCoord. Time from HIV seroconversion to reaching CD4 thresholds <200, <350 and <500 cells/mm³; assessment of need following changes in treatment guidelines. Clin Infec Dis 2011;53:817-825. [PubMed]

Read more about EuroCoord


August 2011

Importance of timely initiation of combination antiretoviral therapy (cART) to prevent the major AIDS-defining cancers

Looking specifically at Kaposi Sarcoma (KS) and non-Hodgkin lymphoma (NHL), the authors used data on 689 cases and 4,588 controls and found that an initially low and decreasing CD4 cell count during the year prior to diagnosis was predictive of both malignancies. The association between a weak and weakening immune system and cancer risk was significant even when the analysis was restricted to the period after 2000, when cART was widely available.

However, the study also showed that the incidence of both cancers increased in patients who had initiated cART in the previous 3 months (odds ratio 2.31; 95% confidence interval 1.33, 4.00) after adjusting for immune deficiency. The authors highlight that “most of this increased cancer risk is explained by the immunodeficiency characteristic of the period before cART initiation.”

They add “there may be some additional risk resulting from immune reconstitution during the first few months after cART initiation.”

Immune reconstitution inflammatory syndrome (IRIS) is typically characterised by clinical deterioration shortly after the start of treatment and is often classified as either paradoxical worsening of existing untreated disease or the ‘unmasking’ of previously subclinical disease. IRIS most often presents with an opportunistic infection, especially TB.   

The equivalent forms of IRIS in patients with KS would include an increasing number or size of lesions that were present before cART (‘flare’) or the diagnosis of KS soon after beginning cART.

The authors conclude, “On the basis of our findings, however, the main risk factor for the appearance of these malignancies is immunodeficiency; and, therefore, the timely initiation of cART remains the best strategy to avoid the development of these malignancies.”

Jaffe H, De Stavola B, Carpenter L, Porter K and Cox D. Immune reconstitution and risk of Kaposi sarcoma and non-Hodgkin lymphoma in HIV-infected adults. AIDS 2011. 25:1395-1403. [Pubmed]

 Read more about the study on the EATG, aidsmap, and IAS websites.

 Read more about EuroCoord

October 2010

Abstract accepted for HIV10 Congress

An abstract entitled Long-term probability of detecting drug-resistant HIV in patients starting antiretroviral therapy within the first year of HIV infection by Sara Lodi has been accepted as an oral presentation by the HIV10 Congress which takes place in Glasgow in November 2010.



July 2010

Antiretroviral treatment benefits are evident below CD4 count of 500, uncertain above this level

Starting antirertoviral therapy with a CD4 count between 350 and 500 reduces the likelihood of HIV disease progression and death relative to initiation below 350.

These findings from CASCADE data were presented at the Eighteenth International AIDS Conference in Vienna.

Read the full story on the NAM website.



March 2010

Abstracts accepted 

The following abstracts have been accepted for XVIII International AIDS Conference to be held in Vienna in July 2010:

• HIV controllers with a known date of seroconversion - What happens before and during HIV control, results from CASCADE - Yoann Madec (poster presentation)

• The characterisation of long-term non-progression of HIV-1 infection since seroconversion - Jannie van der Helm (oral presentation)

February 2010

Knowledge of the current CD4 cell count is sufficient when deciding whether to initiate antiretroviral therapy in symptom-free HIV patients

A paper published today in PLoS Medicine using CASCADE data has shown that there is no need to take into consideration the CD4 slope prior to the start of HIV therapy when deciding whether to initiate therapy.
 
Wolbers et al considered whether there was any evidence of an association between pre-therapy CD4 slope and the primary outcome (a first new AIDS-defining event or death).
 
A total of 2,820 HIV-positive patients initiating cART were included in the study; the average pre-cART CD4 cell decline among them was 61 cells/ml/year. Of these, 255 experienced a new AIDS-related event or died after starting cART but the researchers found no evidence for an association between the primary outcome and the pre-cART CD4 slope or between survival and this slope. In addition, the rate of CD4 cell count decline was not significantly associated with progression to AIDS or death among 1,731 HIV-positive, symptom-free patients with CD4 cell counts above 350 cells/ml who were studied before cART was developed.
 
As well as showing that the rate of CD4 decline will not improve the prediction of clinical outcome, the findings also suggest that the rate of decline in individual patients is extremely variable over time. So, a rate measured at one time point cannot be used to predict the CD4 count in the future.
 
The findings of this study strongly suggest that knowledge of the current CD4 cell count and an assessment of other established risk factors for progression to AIDS are sufficient when deciding whether to initiate therapy in symptom-free HIV-positive patients.
 
Read the paper online.



December 2009

ACTIVATE Training course
The 4th International ACTIVATE training course for HIV clinicians is being held in Tallinn, Estonia from 10-12 March 2010. This course is free to delegates - registration and accommodation is included, and travel costs will be reimbursed. Click here to view the flyer.

The training will target HIV clinicians from Central and Eastern Europe and will include modules on management of TB, HCV & HBV co-infection, opportunistic infections, pregnancy and children, as well as epidemiological concepts for clinicians. The format will be a mixture of lectures, case reporting, and discussion, and will be mainly in English. Simultaneous Russian translation will also be provided and course material will be available to all delegates in both English and Russian.
 
ACTIVATE is funded by a grant from the European Commission so there are, therefore, no course fees.  All costs, including travel, hotel accommodation for 2 nights, and meals will be included at no cost to delegates.
 
If you would like an application form, please email the administrator. Please note that all application forms must be returned completed by 17^th February 2010.  Places will be allocated on a first-come, first-served basis, with preferential registration for more junior grades.


November 2009

The  following abstracts have been accepted for the 17th Conference on Retroviruses and Opportunisitic Infections taking place in San Francisco:

• Sara Lodi - Proportion of individuals likely to need treatment for CD4 thresholds <200, <350, and <500 cells - poster presentation.
• Sara Lodi - Concordance of recent HIV infection between 3 STARHS assays is not dependent on patient characteristics - poster presentation and themed discussion presentation.
• Jannie van der Helm - The hepatitis C epidemic among HIV-positive men who have sex with men started before 2000 - poster presentation.
• Nikos Pantazis - Longitudinal CD4 cell count evolution during HIV natural history: Comparison between European and sub-Saharan African seroconverter cohorts - poster presentation.
• Inma Jarrin - Differences in time to AIDS and death following seroconversion according to geographical origin - poster presentation

We are also pleased to announce that two of our partners, Inma Jarrin and Jannie van der Helm have each won a Young Investigator Award.

June 2009

The 3rd International ACTIVATE HIV course will be held in Minsk, Belarus 10th - 12th September 2009. NEAT is providing funding for 50 scholarships for Eastern European partners. The scholarships will cover the cost of the course, travel, visa, hotel and per diem. For further information click here. The application form can also be downloaded here.


May 2009

The following abstracts have been accepted:

• van der Helm J, Geskus RB, del Amo J, Porter K, Prins M on behalf of CASCADE Collaboration. The hepatitis C epidemic among HIV-positive men who have sex with men started before 2000. Accepted as a poster presentation at the 18th International Society for STD Research Conference, 28th June - 1st July 2009, London. 

• Lodi S, Porter K, Phillips A, on behalf of the CASCADE Collaboration. Time to reaching CD4≤500 for individuals followed up since HIV seroconversion. Accepted as a poster to the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 19th-22nd July 2009, Cape Town.

• Ewings F, Walker AS, Porter K, Copas A. Using causal models to determine optimal dynamic treatment regimes with a time-to-event outcome. Accepted as an oral presentation at the 30th Annual Conference of the International Society for Clinical Biostatistics, 23rd - 27th August 2009, Prague.

• van der Wal W, del Amo-Valero J, Porter K, Perez-Hoyos S, Prins M, Geskus RB, on behalf of the CASCADE Collaboration. Causal effect of AIDS-defining conditions on mortality modified by HAART use and calendar time. Accepted as an oral presentation at the 30th Annual Conference of the International Society for Clinical Biostatistics, 23rd - 27th August 2009, Prague.

February 2009

One poster was presented at the 16th Conference on Retroviruses and Opportunistic Infections held this year in Montreal:

• Drylewicz J, Walker S, Commenges D, Pillay D, Venet A, Masquelier B, Meyer L, Chêne G, Porter K, Thiébaut R, and the CASCADE Collaboration. Plasma HIV RNA and CD4+ count dynamics during acute infection in 761 HIV-1-infected patients: The CASCADE Collaboration [Poster]

The following abstracts have been accepted by the International Workshop on HIV Observational Databases being held in Lisbon, Portugal in March 2009:

1. Wolbers M, Babiker A, Dorucci M, Sabin C, Chêne G, Mussini C, Porter K, Bucher H on behalf of the CASCADE collaboration. Pre-treatment CD4 slope and progression to AIDS or death in naïve HIV-infected patients initiating cART: The CASCADE Collaboration [oral presentation]
2. Lodi S, Touloumi G, Babiker A. Issues in estimating CD4 decline in seroconverter and seroprevalent studies: a simulation study [poster]
3. Lodi S, Porter K, Guiguet M, Costagliola D, Fisher M, de Luca A and the CASCADE Collaboration. Incidence of Kaposi's Sarcoma and survival following its diagnosis in HIV-infected gay men followed up since seroconverion [poster]
4. Touloumi G, Pantazis N, Lodi S, Porter K. The impact of short course cART in primary infection on viral suppression and immunologic response in later treatment [poster]

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December 2008

CASCADE laboratory exchange programme

A laboratory exchange programme was set up in 2008 to enable CASCADE partners from Central and Eastern European laboratories to be introduced to, and develop skills in, various HIV techniques. Participants from Estonia, Poland, Russia and the Ukraine were hosted within laboratories in Italy (Dr Claudia Balotta), Germany (Dr Claudia Kücherer), Denmark (Dr Louise Bruun Jørgensen) and the UK (Dr Stéphane Hué) for 1-2 weeks. A wide range of techniques were covered in that period, from virus extraction and amplification to sequence analysis, co-receptor usage, HIV genotyping from Dried Blood Spots, as well as dry-laboratory techniques from phenotypic analyses to determine drug susceptibility through to the construction of phylogenetic trees. All participants reported that they found the visits extremely useful, not just because it will facilitate the successful introduction of new techniques in their own laboratories, but also because it enabled important research links to be established.

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Next CASCADE workshop

The next CASCADE workshop will be taking place in Barcelona on Thursday 14th and Friday 15th May 2009. 

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March 2008

The 2nd International ACTIVATE HIV Course: 8th - 9th November, Glasgow 2008 

This exciting clinical training course is part of the ACTIVATE initiative and precedes the Ninth International Congress on Drug Therapy in HIV Infection. Clinicians from central and eastern Europe are particularly encouraged to participate. The course is aimed at doctors and pharmacists, either practicing or in-training. Click here for more information and how to register.

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February 2008

Competing Risks Guide

A Competing Risks guide is now available to download here. This is a freely available guide which should be cited as: A Practical Guide on Modeling Competing Risk Data by Giorgos Bakoyannis and Giota Touloumi on behalf of CASCADE Collaboration. www.cascade-collaboration.org. Downloaded on [insert date of download].

New EuroCOORD website

EuroCOORD now has a dedicated website www.eurocoord.net. The January 2008 newsletter is available here.

15th Conference on Retroviruses and Opportunistic Infections (CROI)

The following abstracts were accepted for the 15th CROI conference held in Boston 3rd – 6th February 2008: 

• The effect of antiretroviral treatment of different durations in primary HIV infection (poster presentation). 

• Changes over time in the risk of death following HIV seroconversion compared with mortality in the general population (oral presentation).
  

12th International Workshop on HIV Observational Databases

The following abstracts have been accepted for the 12th International Workshop on HIV Observational Databases to be held in Malaga 27th - 30th March 2008: 

• Relationship between immunodeficiency and specific non-AIDS causes of death: different approaches using the CASCADE Collaboration (oral presentation).

• Modelling pre- and post-HAART CD4: analysis on possible association between pre- and post-HAART slopes.

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July 2007

3 posters using CASCADE data were presented at the 2007 IAS Conference held in Sydney:

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June 2007

The next CASCADE workshop will be held at the Radisson Hotel in Krakow, Poland on the 8-9th May 2008.

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December 2006

Welcome to CASCADE’s new website!

We hope you find the new website useful and easier to navigate.

It has been primarily developed to provide a link between CASCADE partners and to keep them updated on project progress and output.

It will also include:

The website will also enable partners to submit and retrieve data, proposals and draft manuscripts.

If you have any comments or enquiries regarding the new website please email them to the webmaster.