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NIHR Signal Starting antiretroviral therapy immediately after HIV diagnosis reduces transmission of the virus

Published on 16 January 2018

doi: 10.3310/signal-000530

Giving antiretroviral therapy to people newly diagnosed with HIV may be an effective and cost-effective way of reducing new infections. Increased HIV testing in at-risk populations may identify more people for treatment and also reduce infection rates.

Using data from a number of sources including NIHR funded projects, researchers developed a computer simulation model. The model looked at the relationship between HIV infections, sexual risk behaviours and antiretroviral therapy over a 30 year period. Introduction of antiretroviral therapies and increased condom use were associated with lower rates of new cases. Most new HIV infections arose due to people not yet being aware of their HIV status. Modelling projections suggested that increasing the rate of HIV testing, and initiating antiretroviral therapy from diagnosis could both reduce the rates of new infections.

However, in the years since antiretroviral therapy has proved effective, sex without a condom has increased among men who have sex with men and is the main route of infection. This is hampering any attempts to reduce the number of people passing on HIV.

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Why was this study needed?

In the UK there are over 100,000 people living with HIV. Each year there are around 4,000 new cases of HIV. Most of these new cases are in men who have sex with men (MSM). Antiretroviral therapy is used to suppress HIV in people who carry the virus. It is also known to reduce the risk of transmission of HIV.

Previously, people did not receive antiretroviral therapy until the HIV infection had reduced the number of certain immune cells. This was defined as having a CD4 count lower than 350/µl. The START randomised trial recently found that there is a clinical benefit to individuals who initiate antiretroviral therapy sooner, when they are first diagnosed with HIV.

This modelling study aimed to look at whether earlier initiation of antiretroviral therapy for MSM could also reduce the rate of new HIV infections and if it is cost-effective.

What did this study do?

This health economic modelling study explored the cost-effectiveness of giving antiretroviral therapy to men with HIV from the time they are diagnosed. The researchers used data from five NIHR‑funded studies: three cross-sectional surveys, the START trial and a cohort study. Three studies were from the UK, one included European countries and START was international.

A computer simulation model was developed to examine the relationship between risk behaviours, transmission, disease progression and the effect of treatment from 1980 to 2012. Predictions about infection rates by 2030 were also made when modelling the effects of increased testing, changing the proportion of people on antiretroviral therapy and the timing of starting treatment.

The models assume that levels of condomless sex remain as they were in 2012 which may not be the case.

What did it find?

Looking at data from 1980 to 2012, the computer simulation model found:

  • Initially, the incidence of HIV reduced in response to a decline in condomless sex. Once antiretroviral therapy was introduced, however, condomless sex started to increase which in turn lead to a rise in HIV infection incidence.
  • The previous policy of initiating antiretroviral therapy when the CD4 count was below 350/µl reduced HIV infection incidence. Most (82%) new cases of HIV in that period were infected by people who did not know they had HIV and were therefore not receiving antiretroviral therapy.

Future projections from the model suggested:

  • To reduce HIV infection incidence to less than 1 case per 1,000 person-years, the proportion of MSM living with HIV who are virally suppressed on antiretroviral therapy should increase from 60% to 90%.
  • Increasing the rate of HIV testing to encourage earlier diagnosis would, by itself, reduce new infections. This may be even more effective than the change in policy regarding the timing of antiretroviral therapy initiation.
  • The cost-effectiveness ratio to achieve 90% coverage would be £20,000 at current drug prices. This includes the additional testing that would be required. If the price of antiretroviral therapy reduces to 20% of current prices when generic drugs are available, the cost-effectiveness ratio will drop to £3,500.

What does current guidance say on this issue?

The British HIV Association published an interim update to guidelines on the use of antiretroviral therapy for adults with HIV in 2016. They recommend that everyone with suspected or diagnosed HIV infection is reviewed promptly by an HIV specialist and offered immediate antiretroviral therapy.

This recommendation was made on the basis of randomised controlled trials which showed that immediate antiretroviral therapy provided increased clinical benefit compared with waiting until CD4 counts dropped.

What are the implications?

This study supports recommendations that antiretroviral therapy should be offered immediately to people newly diagnosed with HIV, rather than waiting until the CD4 count falls. As well as providing benefits for the individual with HIV, this will reduce the risk of onward transmission of the virus.

To meet the 90% target, four times as many people need to be tested, which is a major challenge. Also, there needs to be greater public awareness that the growing pattern of men having condomless sex with multiple male partners is hindering the success of approaches to reduce the number of people living with HIV.

Citation and Funding

Miltz A, Phillips AN, Speakman A et al. Implications for a policy of initiating antiretroviral therapy in people diagnosed with human immunodeficiency virus: the CAPRA research programme. Programme Grants Appl Res. 2017;5(18).

This project was funded by the National Institute for Health Research Programme Grants for Applied Research (project number RP-PG-0608-10142).

Bibliography

BHIVA. BHIVA guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2015. London: British HIV Association; interim update 2016.

Why was this study needed?

In the UK there are over 100,000 people living with HIV. Each year there are around 4,000 new cases of HIV. Most of these new cases are in men who have sex with men (MSM). Antiretroviral therapy is used to suppress HIV in people who carry the virus. It is also known to reduce the risk of transmission of HIV.

Previously, people did not receive antiretroviral therapy until the HIV infection had reduced the number of certain immune cells. This was defined as having a CD4 count lower than 350/µl. The START randomised trial recently found that there is a clinical benefit to individuals who initiate antiretroviral therapy sooner, when they are first diagnosed with HIV.

This modelling study aimed to look at whether earlier initiation of antiretroviral therapy for MSM could also reduce the rate of new HIV infections and if it is cost-effective.

What did this study do?

This health economic modelling study explored the cost-effectiveness of giving antiretroviral therapy to men with HIV from the time they are diagnosed. The researchers used data from five NIHR‑funded studies: three cross-sectional surveys, the START trial and a cohort study. Three studies were from the UK, one included European countries and START was international.

A computer simulation model was developed to examine the relationship between risk behaviours, transmission, disease progression and the effect of treatment from 1980 to 2012. Predictions about infection rates by 2030 were also made when modelling the effects of increased testing, changing the proportion of people on antiretroviral therapy and the timing of starting treatment.

The models assume that levels of condomless sex remain as they were in 2012 which may not be the case.

What did it find?

Looking at data from 1980 to 2012, the computer simulation model found:

  • Initially, the incidence of HIV reduced in response to a decline in condomless sex. Once antiretroviral therapy was introduced, however, condomless sex started to increase which in turn lead to a rise in HIV infection incidence.
  • The previous policy of initiating antiretroviral therapy when the CD4 count was below 350/µl reduced HIV infection incidence. Most (82%) new cases of HIV in that period were infected by people who did not know they had HIV and were therefore not receiving antiretroviral therapy.

Future projections from the model suggested:

  • To reduce HIV infection incidence to less than 1 case per 1,000 person-years, the proportion of MSM living with HIV who are virally suppressed on antiretroviral therapy should increase from 60% to 90%.
  • Increasing the rate of HIV testing to encourage earlier diagnosis would, by itself, reduce new infections. This may be even more effective than the change in policy regarding the timing of antiretroviral therapy initiation.
  • The cost-effectiveness ratio to achieve 90% coverage would be £20,000 at current drug prices. This includes the additional testing that would be required. If the price of antiretroviral therapy reduces to 20% of current prices when generic drugs are available, the cost-effectiveness ratio will drop to £3,500.

What does current guidance say on this issue?

The British HIV Association published an interim update to guidelines on the use of antiretroviral therapy for adults with HIV in 2016. They recommend that everyone with suspected or diagnosed HIV infection is reviewed promptly by an HIV specialist and offered immediate antiretroviral therapy.

This recommendation was made on the basis of randomised controlled trials which showed that immediate antiretroviral therapy provided increased clinical benefit compared with waiting until CD4 counts dropped.

What are the implications?

This study supports recommendations that antiretroviral therapy should be offered immediately to people newly diagnosed with HIV, rather than waiting until the CD4 count falls. As well as providing benefits for the individual with HIV, this will reduce the risk of onward transmission of the virus.

To meet the 90% target, four times as many people need to be tested, which is a major challenge. Also, there needs to be greater public awareness that the growing pattern of men having condomless sex with multiple male partners is hindering the success of approaches to reduce the number of people living with HIV.

Citation and Funding

Miltz A, Phillips AN, Speakman A et al. Implications for a policy of initiating antiretroviral therapy in people diagnosed with human immunodeficiency virus: the CAPRA research programme. Programme Grants Appl Res. 2017;5(18).

This project was funded by the National Institute for Health Research Programme Grants for Applied Research (project number RP-PG-0608-10142).

Bibliography

BHIVA. BHIVA guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2015. London: British HIV Association; interim update 2016.

Implications for a policy of initiating antiretroviral therapy in people diagnosed with human immunodeficiency virus: the CAPRA research programme

Published on 14 November 2017

Miltz A, Phillips A N, Speakman A, Cambiano V, Rodger A & Lampe F C

Programme Grants for Applied Research Volume 5 Issue 18 , 2017

Background More than 100,000 people in the UK are living with a human immunodeficiency virus (HIV) infection. There are currently estimated to be around 4000 people newly infected in the UK per year, mostly men who have sex with men (MSM). It has become increasingly clear that antiretroviral therapy (ART) used to treat people infected with HIV also has a profound effect on infectivity. At the initiation of the programme, it was the policy in the UK to initiate ART in people when their cluster of differentiation 4 (CD4) count was approaching 350/µl. Objectives To assess what would be the effectiveness and cost-effectiveness of a policy of immediate initiation of ART at diagnosis among MSM, taking into account the potential reductions in new infections. Design We calibrated an individual-based model of HIV transmission, progression and the effect of ART in MSM, informed by a series of studies on sexual behaviour in relation to ART use and the transmission risk in people with viral suppression on ART, and by surveillance data collected by Public Health England. Setting, participants and interventions The series of studies used to inform the model included (1) the Antiretrovirals, Sexual Transmission Risk and Attitudes (ASTRA) study, a cross-sectional self-administered questionnaire study of people diagnosed with HIV attending eight HIV outpatient clinics in the UK (2011–12); (2) the Cognitive Impairment in People with HIV in the European Region (CIPHER) study, a study of levels of neurocognitive impairment in HIV-positive ASTRA participants and people from HIV clinics in Rome, Copenhagen and Minsk; (3) the Attitudes to, and Understanding of, Risk of Acquisition of HIV (AURAH) study, a cross-sectional self-administered questionnaire study of individuals who have not been diagnosed as HIV-positive attending 20 genitourinary medicine clinics across the UK (2013–14); (4) a substudy of sexual behaviour among individuals enrolled in an open-label multicentre international randomised trial (from 2013) of immediate versus deferred ART (to CD4 cell counts of 350/µl) in people with CD4 cell counts of > 500/µl [the Strategic Timing of Antiretroviral Therapy (START) trial]; and (5) Partners of People on ART: a new Evaluation of the Risks (PARTNER), an observational multicentre longitudinal study of HIV serodifferent heterosexual and MSM couples, in which the HIV-positive partner is on ART (2010–14). Main outcome measures The main outcome measures were the clinical effectiveness and cost-effectiveness of a policy of immediate initiation of ART at diagnosis. Results Based on data from studies (i)–(v), we estimated from our modelling work that increases in condomless sex (CLS) among MSM as a whole may explain the increase in HIV infection incidence in MSM epidemics over a time when ART coverage and viral suppression increased, demonstrating the limiting effects of non-condom use on the HIV epidemic among MSM. Accordingly, an increase in the overall proportion of MSM living with HIV who are virally suppressed on ART from the current level of < 60% to 90% without increases in CLS was required to achieve a reduction in the incidence of HIV among MSM to < 1 per 1000 person-years. The incremental cost-effectiveness ratio associated with the fourfold increase in levels of HIV testing and ART at diagnosis required to provide this increase from < 60% to 90% was £20,000 if we assumed continuation of current ART prices. However, this value falls to £3500 if we assume that ART prices will fall to 20% of their current cost as a result of the introduction of generic drugs. Therefore, our evaluation suggests that ART initiation at diagnosis is likely to be highly cost-effective in MSM at a population level, particularly accounting for future lower ART costs as generic drugs are used. The impact will be much greater if levels of HIV testing can be enhanced. Limitations It was necessary to make some assumptions beyond the available data in order to extrapolate cost-effectiveness through modelling. Conclusions Our findings suggest that ART initiation at diagnosis is likely to be cost-effective in MSM. Of note, after this programme of work was completed, results from the main START trial demonstrated benefit in ART initiation even in people with CD4 cell counts of > 500/µl, supporting ART initiation in people diagnosed with a HIV infection. Future work There is a need for future research into the means of increasing the frequency with which MSM test for HIV. Funding The National Institute for Health Research Programme Grants for Applied Research programme.

CD4 describes the presence of molecules called glycoproteins on the surface of cells in the immune system (T cells). In HIV infection, the number of T cells which have CD4 on their surface starts to decrease as the infection progresses, this is known as the CD4 count.

The cost-effectiveness ratio is the difference in cost between two interventions, divided by the difference in their effectiveness.

Expert commentary

When this project started only those HIV patients with a significant decline in their immune system were offered therapy. Now it is known that all HIV infected individuals benefit from taking anti-retroviral drugs.

What this study adds is to quantify the likely population benefit and also the cost-effectiveness of introducing widespread treatment, which is achieved by reducing the infectivity of each treated patient thus preventing onward transmission of the virus.

The challenge now is to identify infected but not yet diagnosed individuals, who comprise 13% of all infections in the UK, so that they can also be offered treatment.

Jonathan Ross, Professor of Sexual Health and HIV, University Hospital Birmingham NHS Foundation Trust