The clinical outcomes, response to treatment and epidemic dynamics of HIV-1 in the UK
Lead Research Organisation:
University College London
Department Name: Infection and Population Health
Abstract
The characteristics of individuals with HIV in the UK are changing with a much greater number of those living with HIV being women. Treatments for HIV are now very effective and many people infected with the virus are able to live almost normal lives. As a result, not only is the HIV-infected population growing older, but many of the women are starting their own families. Even if these women do not yet require treatment for their own health, they may be treated for short periods of time to prevent their babies from becoming infected with HIV. This treatment is very effective and only a very small number of HIV-infected babies are now born in the UK each year. Treatment may be further complicated among individuals who are also infected with hepatitis C or B virus ? these individuals may require earlier treatment and/or different drug combinations than those who are only infected with HIV.
Despite the benefits of treatment, the drugs may still occasionally fail in an individual. This may be because the individual develops side effects to the drugs, or that they find it difficult to take their drugs at exactly the same time every day. When treatments fail, the virus may become resistant to the drugs that the patient is receiving, and this may have knock-on effects for their future treatment choices. Consequently, doctors have started to change the way in which they treat HIV-infected people; for example, treatment may be started earlier and different drug combinations may be used which aim to reduce the risk of side effects, whilst minimising the risk that a patient?s virus will become resistant. In order to plan the future care for these individuals, we need to monitor the use of treatment in HIV-infected persons, and the outcomes of those who receive it.
Two large ongoing studies in the UK, the UK CHIC Study and the UK HDRD, have been monitoring outcomes (e.g. use of treatment, AIDS events, deaths, development of resistance) in HIV-infected persons since 2001. This proposal requests funding to continue to expand and monitor these cohorts so that the information they provide remains timely and accurate. In addition to monitoring outcomes, we also plan to investigate whether treatment received during pregnancy has any long-term effects on the mother?s health, and whether infection with hepatitis B or C accelerates the progression of HIV disease, or reduces the benefits of treatments.
Despite the benefits of treatment, the drugs may still occasionally fail in an individual. This may be because the individual develops side effects to the drugs, or that they find it difficult to take their drugs at exactly the same time every day. When treatments fail, the virus may become resistant to the drugs that the patient is receiving, and this may have knock-on effects for their future treatment choices. Consequently, doctors have started to change the way in which they treat HIV-infected people; for example, treatment may be started earlier and different drug combinations may be used which aim to reduce the risk of side effects, whilst minimising the risk that a patient?s virus will become resistant. In order to plan the future care for these individuals, we need to monitor the use of treatment in HIV-infected persons, and the outcomes of those who receive it.
Two large ongoing studies in the UK, the UK CHIC Study and the UK HDRD, have been monitoring outcomes (e.g. use of treatment, AIDS events, deaths, development of resistance) in HIV-infected persons since 2001. This proposal requests funding to continue to expand and monitor these cohorts so that the information they provide remains timely and accurate. In addition to monitoring outcomes, we also plan to investigate whether treatment received during pregnancy has any long-term effects on the mother?s health, and whether infection with hepatitis B or C accelerates the progression of HIV disease, or reduces the benefits of treatments.
Technical Summary
The use of highly active antiretroviral therapy (HAART) has had a major impact on the health of HIV-infected individuals in the developed world and, as a result, life expectations of those infected with HIV have started to approach those seen in the general population. However, treatment paradigms are changing and over the next five years we expect to see changes in the drugs/drug combinations used, the order in which they are sequenced and the CD4 count at which treatment is started. However, the development and transmission of resistant HIV remains a threat to successful treatment. Furthermore, those living with are now older, a greater proportion are women (many of whom are becoming pregnant and receiving treatment to prevent transmission of HIV to their baby) and many are co-infected with viral hepatitis; these factors may complicate the management of those with HIV. In order to plan the need for health-care services and to understand the need for new antiretroviral drugs in HIV-infected persons, it is important to continue to monitor the outcomes of treatment in this population, including the incidence and patterns of drug resistance, and to determine the degree to which the efficacy of future drugs is likely to be compromised by resistance development.
The UK Collaborative HIV Cohort (CHIC) Study and UK HIV Drug Resistance Database (UK HDRD) were initiated in 2001 to monitor the uptake and response to HAART among individuals with HIV in the UK, and the development of resistance in these individuals. The main objective of this programme grant application is to continue to follow these two large cohorts (with expansion where possible so that they continue to follow a large and geographically representative group of patients) with the aim of providing timely information on the changing trends over time. In addition, several other questions have arisen which must now be addressed, relating particularly to the use of treatment during pregnancy and the impact of long-term co-infection with hepatitis viruses. Thus, we propose to develop five complementary themes of research (ongoing monitoring of outcomes; understanding the transmission and persistence of resistance; understanding the molecular epidemiology of the UK epidemic; describing the impact on women of antiretroviral treatment received during pregnancy; and describing the impact of co-infection with hepatitis B/C on HIV outcomes). Each theme will include a series of co-ordinated projects covering questions across the broad scientific area.
The UK Collaborative HIV Cohort (CHIC) Study and UK HIV Drug Resistance Database (UK HDRD) were initiated in 2001 to monitor the uptake and response to HAART among individuals with HIV in the UK, and the development of resistance in these individuals. The main objective of this programme grant application is to continue to follow these two large cohorts (with expansion where possible so that they continue to follow a large and geographically representative group of patients) with the aim of providing timely information on the changing trends over time. In addition, several other questions have arisen which must now be addressed, relating particularly to the use of treatment during pregnancy and the impact of long-term co-infection with hepatitis viruses. Thus, we propose to develop five complementary themes of research (ongoing monitoring of outcomes; understanding the transmission and persistence of resistance; understanding the molecular epidemiology of the UK epidemic; describing the impact on women of antiretroviral treatment received during pregnancy; and describing the impact of co-infection with hepatitis B/C on HIV outcomes). Each theme will include a series of co-ordinated projects covering questions across the broad scientific area.
