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EuroCoord supports World AIDS Day

 

Sunday 1 December 2013 marks the 25th annual World AIDS Day which is an opportunity to show  support for people living with HIV/AIDS, to remember those who have died, and to unite in the fight against HIV

 

More than 2.3 million people are currently living with HIV in Europe and an estimated 35 million people worldwide are HIV positive.Over 25 million people between 1981 and 2007 have died from the virus, making it one of the most destructive pandemics in history.World AIDS Day is an important reminder to the public and governments that, although important improvements have been made, several challenges in HIV prevention, management and treatment remain, which are now complicated by an altered economic climate.

 

What is HIV?

 

Human immunodeficiency virus (HIV) infects vital cells of the immune system with one of its main targets being a subpopulation of white blood cells commonly known as CD4 cells.

 

HIV rapidly replicates and untreated HIV infection leads to a progressive loss of CD4 cells making the body vulnerable to a range of life-threatening infections (often called opportunistic infections) and cancers, a condition known as acquired immune deficiency syndrome (AIDS).

 

The number of CD4 cells (CD4 count) and the number of viral copies (viral load) in the blood are the most important markers used for monitoring HIV infection and making treatment decisions.

 

Antiretroviral drugs are used to target different parts of the virus to inhibit its replication in the blood. The aim of treatment is to achieve an undetectable viral load to ensure a healthy immune system.

 

Combination antiretroviral therapy (cART) introduced in 1996 dramatically improved the health of HIV positive people and brought about significant reductions in morbidity and mortality.

   How is EuroCoord helping in the fight against HIV/AIDS?

 

EuroCoord has brought together the biggest HIV research collaborations in Europe to establish the biggest dataset of HIV positive adults and children in the world. Our researchers use this rich source of information to definitively answer questions that could not be addressed through single studies alone.

 

Since EuroCoord was established in 2011, over 60 research papers addressing these key questions in HIV research have been published from members of the network. Here we highlight just a few of the many research successes from the past 12 months.  

 

Progress towards elimination of new infections in Europe

 

Elimination of infant HIV infections by 2015 is one of the ten global UNAIDS targets and the prevention of mother-to-child transmission (MTCT) is a key component of this goal. Most high-income countries have very low rates of MTCT, but in many low- and middle-income countries, women continue to receive sub-optimal treatment to prevent MTCT. Using EuroCoord’s diverse dataset, our researchers have looked at key issues in the prevention of MTCT in Europe.

 

Antenatal cART

One country that has made prevention of MTCT a public health priority is Ukraine. In November 2007, the country’s Ministry of Health recommended the national implementation of the World Health Organization’s Option-B strategy – i.e. treating the woman with cART regardless of her CD4 count.

 

EuroCoord researchers investigated the uptake of this recommendation and the impact on the rate of MTCT.1 They found that antenatal cART coverage increased significantly, from 22% of deliveries  in 2008 to 61% in 2010.

 

Access to antenatal cART improved substantially, but implementation of the Option-B policy was slow. Compared with monotherapy, they found that cART was associated with a 70% greater reduction in the risk of MTCT. The researchers concluded that for MTCT to be eliminated in Ukraine, improvements in the retention of women in HIV care and further roll-out of WHO Option B are urgently needed.

 

Missed opportunities for a vaginal delivery

In the pre-cART era, elective caesarean section (CS) was a key intervention to prevent MTCT. However, now that MTCT rates have dramatically decreased with use of cART in pregnancy, there appears to be little benefit in delivering by this route for women with undetectable viral load. The risks associated with delivering by CS include an increased rate of complications and increased morbidity in future pregnancies, together with higher cost. European guidelines, therefore, recommend vaginal deliveries for HIV positive women with an undetectable or very low viral load (VL). Using EuroCoord data from over 3,000 deliveries between 2000 and 2010, the impact of these guidelines on the rates of vaginal deliveries among HIV positive women in Europe was explored.2

 

The researchers found that, although cART was used in 73% of pregnancies and an undetectable viral load was achieved in 86% of pregnancies, the proportion of women with undetectable VL having a CS was 55% after implementation of the new guidelines. This study highlights the issue of missed opportunities for HIV positive women to have a vaginal delivery, and its associated cost and health implications. 

 

Prognosis and long-term outcome

 

Despite great strides in treatment, the number of people living with HIV and dying from AIDS and HIV/AIDS related illnesses continues to rise. Recent EuroCoord research has looked at the wide-ranging factors associated with HIV acquisition and disease progression, from the issue of late presentation through to the interplay between host and viral genetics.   

 

Late presentation

Early diagnosis and treatment of HIV is associated with better health outcomes and a reduction in onward transmission. Approximately 40%–60% of HIV-positive people in low-income countries continue to be diagnosed late, defined as a person presenting to a clinic with a CD4 count of below 350 cells/mm3 or an AIDS-defining illness within 6 months of diagnosis. EuroCoord data from over 84,000 HIV positive people from 35 European countries between 2000 and 2011 were used to describe trends in late presentation, and assess its clinical consequences.3

 

The study found that 54% of patients were diagnosed late, and 33% presented very late (defined as a person presenting to a clinic with a CD4 count of below 200 cells/mm3 or an AIDS-defining illness within 6 months of diagnosis). Rates of late presentation remained high in heterosexual men (66%) and women (57%), and people of African origin (65%). Although a downward trend was seen from 2000, in 2010/2011 just over half (52%) of patients were presenting late for care. Late presentation was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis. Despite decreases in the rate of late presentation, it still remains an issue across Europe highlighting the need for public health programmes to encourage early testing and improve retention into care.

 

AIDS-defining illnesses at higher CD4 counts

With improvements in therapy, HIV positive people are maintaining higher CD4 counts, but few studies have described the incidence of AIDS-defining illnesses (ADIs) at CD4 counts of 500 cells/mm3 and above. Using EuroCoord data from over 200,000 HIV positive people from 33 European cohorts, researchers looked at the incidence of specific ADIs at CD4 counts of 200 cells/mm3 and above, according to the latest measurement across a wide range of CD4 counts.4 The researchers also wanted to determine the factors associated with developing a new ADI at higher CD4 counts of 500 cells/mm3 and above.

 

They found that the incidence of specific ADIs varied widely among people with current CD4 counts of 200–499 cells/mm3 and was generally low at higher CD4 counts. Despite a low rate at current CD4 counts ≥500 cells/mm3, the rate of new ADIs, particularly cancers, was increased by 20% when compared to those with a current CD4 of 750–999 cells/mm3, whereas there were no further significant reductions in ADIs at higher CD4 counts. This study shows that, although great health improvements have been made because of effective therapy, HIV positive people are not fully immune reconstituted until their CD4 count increases to more than 750 cells/mm3.

 

Impact of viral subtype

One of the characteristics of HIV is its high genetic variability. The different variants of HIV, called subtypes, have different distributions across geographic regions and risk groups. The most prevalent subtype in Europe is subtype B but others have emerged, especially among people who acquired HIV through sex between men and women. EuroCoord data from over 3,000 HIV positive people were used to assess the likely impact of subtype on the levels of CD4 cells just after infection, the rate of their decline and viral load.5

 

The researchers found significant differences in the change in CD4 levels after infection between subtypes. To illustrate the differences, the authors estimated that the mean CD4 loss at the first 2 years after infection would be 88, 142, 100, 130, 103, and 167 cells/µL for subtypes A, B, C, CRF01_AE, CRF02_AG, and G, respectively. These results indicate that viral genetic diversity is likely to play a role in an individual’s disease progression and suggest that the introduction of certain subtypes into a new population, as is being witnessed in Europe, could lead to changes in the natural history of HIV infection.

 

HIV controllers

Previous studies have identified a small number of HIV positive patients who are able to spontaneously control their HIV infection for several years. Known as HIV controllers (HIC), these people do not require treatment because they are able to maintain viral replication at an undetectable level. EuroCoord data were used to describe the natural history of HIV control and to identify factors associated with its duration.6

 

Looking at data from over 9,000 HIV positive people, the study found that 1% was able to establish control of infection. For most of these people control occurred rapidly after infection, but a total of 25% required three years to establish control.  Representing the largest number of HIV controllers followed after infection, this study also found that control was sustained in some patients even while their CD4 count was below 500 cells/mm3. This opens up important new perspectives on the factors underlying HIV control.

 

 

Co-infections

 

With effective treatment, HIV positive people are increasingly more likely to die from non-HIV causes including co-infections such as tuberculosis (TB) and hepatitis C virus (HCV). TB is the most common infection in people living with HIV, and HCV-associated liver failure is now the most common cause of death in people living with HIV in Southern Europe. Using well-established research links and our rich dataset, EuroCoord researchers have been able to assess the impact of these co-infections on HIV disease progression.

 

TB

Although deaths from TB have fallen in HIV positive people since the introduction of effective treatment, the reduction has not been as remarkable as for other infections. TB can be diagnosed at relatively high CD4 counts and the risk of TB among HIV positive people in high-income countries is increasing. EuroCoord data were used to assess TB incidence rates following HIV infection and before starting treatment.7 The aim was to evaluate if the risk of TB following treatment differs from the risk in early HIV infection when the immune system is still relatively intact. The study also explored the role of current and previous CD4 counts on TB risk after treatment initiation.

 

The researchers found that risk of TB increased with the duration of HIV infection in the pre-cART era. They also found that the risk is lower after the start of treatment compared to the risk immediately after infection. Once treatment was initiated, TB risk was associated with current, not previous, CD4 count. More stringent diagnosis and treatment of latent TB early in HIV infection could, therefore, help to reduce the TB burden in high-income countries.

 

HCV and mortality

Although previous studies have shown that HIV infection might accelerate HCV-related liver disease, the significance of HCV-RNA levels remains unclear. Other studies have also indicated that the genotype of the infecting HCV might impact on disease progression.

 

Using EuroCoord data from almost 15,000 HIV positive patients, the effect of HCV-RNA levels and genotype was assessed. The study found that more than half of the HCV positive patients carried HCV genotype 1 (52.9%), followed by 29.7%, 14.2%, and 3.3% frequencies for genotypes 3, 4, and 2, respectively.8 Contrary to some other studies, the researchers found no association between HCV genotype or HCV-RNA levels and the risk of dying from any cause, or liver-related death.

 

For patients who were HCVAb positive (had HCV antibodies in their blood indicating that they have been infected with HCV in the past) the study showed a higher rate of death from any cause, and a nine-fold increase in liver-related deaths compared with HCVAb negative patients. Looking specifically at those HCV positive patients who had undetectable levels of HCV (suggesting that they had either been treated successfully or that their body had been able to control the virus), the incidence of liver-related deaths was five times higher than in HCV negative patients. This finding indicates that patients with resolved HCV infection still remain at increased risk of liver-related death compared to non-HCV-infected HIV patients, and highlights the need for improved treatment options and close clinical management.

 

There is conflicting evidence as to whether HCV co-infection accelerates disease progression. Using EuroCoord data from the pre-cART and cART eras, researchers aimed to determine the effects of co-infection on mortality from all causes and specifically from HIV and/or AIDS, and hepatitis or liver disease, adjusting for the duration of HIV infection.9

 

Using data from 2,000 HIV/HCV co-infected people, they found that in the cART era, co-infected people had significantly higher mortality from all causes compared to those only infected with HIV, 35% compared with 11% respectively, 15 years after infection with HIV. Co-infected people had a much higher risk of hepatitis or liver-related mortality compared with monoinfected individuals in both the pre-cART and cART eras as well as a higher HIV- and/or AIDS-related mortality in the cART era. This study highlights the importance of early diagnosis of HCV infection in HIV positive people as well as interventions to increase the uptake of HCV treatment.

 

Beyond World AIDS Day

 

Although World AIDS Day is a good opportunity to raise awareness of the issues surrounding HIV/AIDS, the work of EuroCoord ensures that it remains at the forefront of the European research agenda all year round.

 

For more information about our research please explore the aims page and visit our news and publications pages.

 

References

 

1. Bailey H, Townsend C, Semenenko I, Malyuta R, Cortina-Borja M and Thorne C for the Ukraine European Collaborative Study Group in EuroCoord. Impact of expanded access to combination antiretroviral therapy in pregnancy: results from a cohort study in Ukraine. Bulletin of the World Health Organization 2013;91:491-500.[PubMed]

Also in WHO Bulletin,Full story on EuroCoord website

 

2. Aebi-Popp K, Mulcahy F, Glass TR, Rudin C, Martinez de Tejada B, Bertisch B, Fehr J, Grawe C, Scheibner K, Rickenbach M, Hoesli I, Thorne C; for the European Collaborative Study in EuroCoord and the Swiss Mother & Child HIV Cohort Study. Missed opportunities among HIV-positive women to control viral replication during pregnancy and to have a vaginal delivery. J Acquir Immune Defic Syndr. 2013;64:58-65. [PubMed

Also on UNAIDS Science now and aidsmap

 

3. Mocroft A, Lundgren J, Sabin M, d'Arminio Monforte A, Brockmeyer N, Casabona J, Castagna A, Costagliola D, Dabis F, De Wit S, Fätkenheuer G, Furrer H, Johnson A and Ole Kirk, for theLate Presenters Working Group, on behalf of the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study in EuroCoord. Risk Factors and Outcomes for Late Presentation for HIV-Positive Persons in Europe: Results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE). PLoS Medicine [Epub ahead of print]

Also on aidsmap and IAS website. Full story on EuroCoord website

 

4. The Opportunistic Infections Working Group of the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study in EuroCoord. The incidence of AIDS defining illnesses (ADIs) at a current CD4 count >=200/mm3 in the post combination antiretroviral therapy era. CID 2013. 57:1038-47. [PubMed]

Also on aidsmap. Full story on EuroCoord website

 

5. Touloumi G, Pantazis N, Chaix ML, Bucher HC, Zangerle R, Bakken Kran AM, Thiebaut R, Masquelier B, Kucherer C, d’Arminio Monforte A, Meyer L and Porter K for CASCADE Collaboration in EuroCoord. Virologic and immunologic response to cART by HIV-1 subtype in the CASCADE Collaboration. PLoS ONE 2013; 8(7):e71174. [Article]

Full story on the EuroCoord website

 

6. Madec Y, Boufassa F, Porter K, Prins M, Sabin C, d’Arminio Monforte A, Amornkul P, Bartmeyer B, Sannes M, Venet A, Lambotte O and Meyer L on behalf of the CASCADE Collaboration in Eurocoord. Natural History of HIV control since seroconversion Experience. AIDS. 2013 Sep 24;27(15):2451-60.[PubMed]

 

7. Lodi S, del Amo J, D’Arminio Monforte A, Abgrall S, Sabin C, Morrison C, Furrer H, Muga R, Porter K, Girardi E, and theCASCADE collaboration in EuroCoord.Risk of tuberculosis following HIV seroconversion in low-burden tuberculosis countries. Thorax 2013;68:207-13. [PubMed]

 

8. Rockstroh J, Peters L, Grint D, Soriano V, Reiss P, d’Arminio Monforte A, Beniowski M, Losso M, Kirk O, Kupfer B, Mocroft A, for EuroSIDA in EuroCoord. Does hepatitis C viremia or genotype predict the risk of mortality in individuals co-infected with HIV? J. Hepatology 2013; 59:213-220. [PubMed]

 

9. Van der Helm J, Geskus R, Sabin C, Meyer L, del Amo J, Chêne G, Dorrucci M, Muga R, Porter K, Prins M on behalf of CASCADE collaboration in EuroCoord. Effect of HCV infection on cause-specific mortality following HIV seroconversion before and after 1997. Gastroenterology 2013;144:751-760. [PubMed]

Also on UNAIDS website

 

 

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