50% of UK seroconverters start ART within 1.4 years of infection: treating during primary infection should be a patient choice
27 May 2014. Related: Conference reports, Antiretrovirals, Treatment strategies, BHIVA/BASHH 3rd Liverpool 2014.
Simon Collins, HIV i-Base
Latest data from the UK seroconverters register highlighted the importance for people diagnosed during primary HIV infection (PHI) to have the option for early treatment.
Currently, the 6-month window period during which HIV-specific immune response are often retained, is often lost due to the misplaced belief that treatment may not be needed for many years.
The UK HIV Seroconverters Register enrols adults diagnosed within 12 months of likely infection date, with this confirmed by either RITA/STARHS or a prior recent negative HIV test.
As such, it provides an important dataset for tracking natural history of infection prior to treatment, responses to treatment and for questions related to seroconversion itself. The BHIVA conference included a review from this cohort on changes in CD4 counts and trends in the time to starting ART since the cohort was first established. [1]
This analysis was based on 1734 people enrolled in the rsgister since 1998 (all diagnosed within 12 months of infection), with increasing numbers of patients over time. Approximately 17% of the total cohort was diagnosed within a month of infection (during seroconversion).
The analysis also uses the term ‘seroconversion interval’ for estimating the time between the last negative and the first positive HIV test, with median seroconversion interval of 151 days (IQR 39, 294). The cohort involves largely male participants (94%), with median age at seroconversion of 33 years (IQR 27 – 40).
This analysis reported that the median CD4 count at ART initiation increased from 284 cells/mm3 (IQR 190, 378) prior to 2000 to 375 cells/mm3 (IQR 296, 511) in 2010-11. However, the ranges for nearly all years varied from <50 to >600 cells/mm3. The range indicates wide use of treatment both within and outside BHIVA guideline recommendations. The slightly higher CD4 count over time (approximately 6 cells/mm3 higher per year in univariate analysis, p < 0.001) might be expected, given that the guidelines have increased the CD4 threshold for starting treatment over the same period. This data needs also to be verified in multivariate models.
In a sub-analysis of 967 people who were diagnosed within 6 months of infection, the percentage of people starting treatment during primary HIV infection also varied over time, reflecting both changing research data and guidelines: steadily dropping from 50% in 2000-1 to 13% in 2008-9 but increasing to 20% for 2010-11.
More significantly, the median time from seroconversion to starting ART steadily reduced from 3.7 years (95%CI: 3.2, 4.9) before 2000 to 1.4 years (95%CI: 1.3, 1.7) in 2010-11 (see Table 1). This is a much shorter period than most people expect: 25% of participants started within 0.7 years and 75% started within 2.8 years.
This shows that the majority of people diagnosed in early infection in the UK start treatment within two years. For the most recent data from 2010-11, the CD4 count when starting treatment was >500 for 25% of people but less than 350 for 50%. These results largely predate the wider use of earlier treatment to reduce infectiousness.
Also, in line with changes in guidelines, far fewer people who started treatment in the first 6 months of infection later stopped treatment (dropping from as high as 80% prior to 2008 down to only 11% since 2008). Prior to 2008, ART was mainly used as a short intervention with median time on ART of approximately 6 months (based on sub-analysis of n=967).
| Year | Pre 2000 | 2000-1 | 2002-3 | 2004-5 | 2006-7 | 2008-9 | 2010-11 |
|---|---|---|---|---|---|---|---|
| n | 194 | 244 | 246 | 254 | 224 | 225 | 347 |
| Years to ART (95%CI) | 3.7(3.2, 4.9) | 2.8(2.2, 3.5) | 2.9(2.3, 4.0) | 2.6(2.2, 3.0) | 2.3(1.8, 2.7) | 2.2(1.8, 2.7) | 1.4(1.3, 1.7) |
| CD4 at ART (IQR) | 284(190, 378) | 280(221, 410) | 297(227, 380) | 314(241, 450) | 330(272, 412) | 337(282, 437) | 375(296, 511) |
| Year | Pre 2000 | 2000-1 | 2002-3 | 2004-5 | 2006-7 | 2008-9 | 2010-11 |
| n | 61 | 98 | 114 | 175 | 148 | 139 | 232 |
|---|---|---|---|---|---|---|---|
| % starting ART during primary infection * | 27.9 | 50.0 | 35.1 | 29.1 | 20.3 | 13.0 | 19.8 |
| % stopping <12 mo | 47.1 | 59.2 | 70.0 | 80.4 | 83.3 | 11.1 | 10.9 |
* Primary infection defined as within 6 months of infection.
Comment
The temporal changes in use of ART appear modest and are against a background of guideline changes over this time.
But, the recent data for time to starting treatment should alert doctors to the importance of offering early ART to people who are diagnosed in primary infection (within 6 months of infection).
This study shows that deferring treatment based on an expectation of having five or more years without treatment, is no longer supported by UK data.
Conversely, potential benefits of treating acute infection include:
- Reduce viral evolution and diversity
- Limit the reservoir of latently infected resting CD4 cells
- Potential benefit from future advances in cure research
- Retaining HIV-specific immune profile similar to long term slow progressors
- Replicate circumstance reported in the VISCONTI cohort
- Reduce infectiousness for sexual partners (‘normalise’ HIV impact on this area of life)
The immunologic benefits of treating during the six-month window are very different to earlier treatment at some later point during chronic infection. Also, given the increased focus on cure research, this is an option for which people should be able to decide for themselves.
The VISCONTI cohort reported that a small number of patients have been able to discontinue ART and maintain viral suppression, in some cases for over a decade. These individuals used ART for several years, started during acute infection. [2]
The Seroconverters Registry data shows that an expectation of five years without needing treatment is not appropriate for people diagnosed in early infection. Indeed, for more than 75% of people this is well under two years.
In line with BHIVA guidelines, the option to use earlier treatment during primary infection should be actively offered to all patients, including people with recent infection, and including those with CD4 counts >500 cells/mm3.
However, while BHIVA guidelines are clear, the i-Base phoneline service has been contacted over several recent cases of people diagnosed during acute infection where the option of early treatment was neither offered nor discussed.
References:
- Parsons V et al. Temporal trends in cART initiation amongst HIV seroconverters in the UK. Oral abstract 08.
http://www.bhiva.org/documents/Conferences/2014Liverpool/Presentations/140402/VictoriaParsons.pdf
http://www.bhiva.org/140402VictoriaParsons.aspx - Sáez-Cirión A et al. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathogens, 14 March 2013. DOI: 10.1371/journal.ppat.1003211.
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003211