Short abstract
A distinct entity requiring distinct counselling
Keywords: HIV
Primary HIV‐1 infection (PHI) has again become a hot topic in HIV research. This relates to the lack of consensus on the management of PHI, and partly because studying transmission and the events early in infection may aid the understanding of HIV‐1 pathogenesis. As such, clinics are currently actively case finding PHI for participation into randomised control studies, such as the international study, SPARTAC.1 Identifying cases of PHI is also now easier because of the wider availability of improved diagnostic techniques such as proviral DNA polymerase chain reaction and the detuned antibody assay (B clade only). In addition, it is hoped that with improved public awareness of sexual health, more active HIV testing by clinics and the availability of the rapid HIV test (Pocit), more individuals will regularly test for HIV and any cases of PHI will therefore be detected more easily.
A recent article in the New England Journal of Medicine summarised the management of newly diagnosed HIV, but did not specifically mention primary infection.2 There are, however, particular issues that arise only at PHI; (i) counselling for prognosis, (ii) antiretroviral treatment, and (iii) transmission, which make it important to distinguish from newly diagnosed chronic infection. An appreciation of these factors by all genitourinary medicine physicians is therefore extremely important.
Counselling for prognosis
All new HIV positive patients want a prognosis. At PHI this can be problematic, particularly as the most accurate predictors of clinical outcome—namely, the rate of CD4 decline and the speed to achieving,3 and magnitude of, viral set point,4 are not available. The time between diagnosis of PHI and achieving a steady state is unclear and varies greatly between individuals.3 Other factors such as the severity and duration of seroconversion symptoms,5,6,7,8 in particular fever and neurological involvement,9,10 a delayed evolution of antibody response,7 older age,11 and concurrent infection with both HIV and CMV12,13 offer little quantitative information and serve only as non‐specific indicators of a more rapid disease progression. Baseline CD4 cell count11 is not useful as PHI represents an extremely dynamic period during which parameters vary considerably.
Citing any HIV cohort data such as MACS11 or CASCADE14 at PHI is particularly problematic as individuals presenting at this stage may represent a self selecting population and have a progression profile that is not representative of all HIV infected individuals, especially if they are presenting with symptomatic seroconversion.
Antiretroviral treatment
The decision whether to prescribe antiretroviral therapy (ART) at PHI is currently not evidence based and this is reflected in the UK guidelines.15 Theoretically, considerations when starting ART at this time are either to treat the symptoms of seroconversion or to improve clinical outcome; the role of ART in either situation is debated.16,17 In our experience treatment of symptoms has rarely been necessary. Such cases are rare and the majority of individuals need reassurance that their symptoms are temporary and are the manifestation of HIV seroconversion rather than being consistent with AIDS or permanent immunosuppression. A low CD4 count itself is not an indication for ART at diagnosis, as it would be expected to start increasing within approximately 3 months.18
The use of ART in order to improve clinical outcome remains unproved. Preservation of HIV specific CD4+ immunity in response to ART at PHI has been described but the longevity and relation to clinical outcome is questioned.19,20 A randomised control study is now under way (SPARTAC) and individuals presenting with PHI should be given the opportunity to participate. Concerns that some individuals are not emotionally able to participate in a study so soon after receiving their HIV positive diagnosis are unfounded in our experience; participation rates have been extremely high, adherence to medication exceptional, and the development of de novo resistant mutations absent.1 Furthermore, taking part in a clinical trial has the additional benefits of more intensive support over a difficult physical and emotional time.
Transmission
Issues around HIV transmission are particularly pertinent to address in patients presenting with PHI and do require additional counselling. Many individuals have a clear understanding of whom they may have contracted HIV from and experience feelings of anger and guilt for having allowed themselves to become infected, as well as anger towards the person or persons who they perceive may have infected them. The legal aspects of this situation are complex; however, with genotyping more widely available it is possible that this issue could arise more frequently. Preventing ongoing transmission at PHI is of paramount importance as individuals are hyper‐infectious21 and may contribute disproportionately to the ongoing epidemic.22,23 Interventions to consider include ART owing to reduce infectiousness, treatment of concomitant STI, and the promotion of immediate changes in sexual behaviour. The former is unevaluated and the latter difficult to achieve.24
In conclusion, discussions on prognosis at PHI may be inaccurate and potentially misleading to individuals. Such discussions should therefore be delayed at least until a viral set point has been reached which can take up to a year after seroconversion.3 Instead, the immediate period following diagnosis may be more effectively used by considering ART as part of a clinical trial (SPARTAC),1 addressing emotional requirements and to promote immediate changes in sexual behaviours in order to limit onward transmission during this period of hyper‐infectiousness.
Key messages
It is important to identify primary HIV infection to prevent the onward transmission of HIV during this hyper‐infectious period
There is currently no evidence base to either support or refute the prescription of antiretroviral therapy at Primary HIV infection and hence any such individual should be offered a clinical trial to powered to investigate this issue.
Giving accurate prognostic information at seroconversion is problematic
Footnotes
This project occurred as a result of 6 years' experience in recruiting individuals diagnosed with primary HIV into an intervention study at St Mary's Hospital that is on going.
References
- 1.Fidler S, Fraser C, Fox J.et al Comparative potency of three antiretroviral therapy regimes in primary HIV infection. AIDS 200620247–252. [DOI] [PubMed] [Google Scholar]
- 2.Hammer S M. Clinical practice. Management of newly diagnosed HIV infection. N Engl J Med 20053531702–10. Review. [DOI] [PubMed] [Google Scholar]
- 3.Blattner W, Ann Oursler K, Cleghorn F.et al Rapid clearance of virus after acute HIV‐1 infection: correlates of risk of AIDS. J Infect Dis 20041891793–1801. [DOI] [PubMed] [Google Scholar]
- 4.Mellors J W, Rinaldo C R, Jr, Gupta P.et al Prognosis of HIV‐1 infection predicted by the quantity of virus in plasma. Science 19962721167–1170. [DOI] [PubMed] [Google Scholar]
- 5.Pedersen C, Lindhardt B O, Jensen B L.et al Clinical course of primary HIV infection: consequences for subsequent course of infection. BMJ 1989299154–157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Keet I P M, Krijnen P, Koot M.et al Predictors of rapid progression to AIDS in HIV‐1 seroconverters. AIDS 1993751–57. [DOI] [PubMed] [Google Scholar]
- 7.Sinicco A, Fora R, Sciandra M.et al Risk of developing AIDS after primary acute HIV‐1 infection. J Acquir Immune Defic Syndr 19936575–581. [PubMed] [Google Scholar]
- 8.Lindback S, Brostrom C, Karlsson A.et al Does symptomatic primary HIV‐1 infection accelerate progression to CDC stage IV disease, CD4 count below 200×106/l, AIDS and death from AIDS? BMJ 19943091535–1537. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Veugelers P J, Kaldor J M, Strathdee S A.et al Incidence and prognostic significance of symptomatic primary human immunodeficiency virus type 1 infection in homosexual men. J Infect Dis 1997176112–117. [DOI] [PubMed] [Google Scholar]
- 10.Boufassa F, Bachmeyer C, Carre N.et al Influence of neurologic manifestations of primary human immunodeficiency virus infection on disease progression. SEROCO Study Group. J Infect Dis 19951711190–1195. [DOI] [PubMed] [Google Scholar]
- 11.Lyles R H, Munoz A, Yamashita T E.et al Natural history of human immunodeficiency virus type 1 viremia after seroconversion and proximal to AIDS in a large cohort of homosexual men. J Infect Dis 2000181872–880. [DOI] [PubMed] [Google Scholar]
- 12.Bonetti A, Weber R, Vogt M W.et al Co‐infection with human immunodeficiency virus‐type 1 (HIV‐1) and cytomegalovirus in two intravenous drug users. Ann Intern Med 1989111293–296. [DOI] [PubMed] [Google Scholar]
- 13.Raffi F, Boudart D, Billaudel S. Acute co‐infection with human immunodeficiency virus (HIV) and cytomegalovirus. Ann Intern Med 1990112234. [DOI] [PubMed] [Google Scholar]
- 14.Collaborative Group on AIDS Incubation and HIV Survival Time from HIV‐1 seroconversion to AIDS and death before the widespread use of highly active anti‐retroviral therapy: a collaborative re‐analysis. Lancet 20003551131–1137. [PubMed] [Google Scholar]
- 15.BHIVA Writing committee on behalf of the BHIVA Executive Committee. The BHIVA treatment Guidelines for 2005 http://www.bhiva.org/guidelines/2005/BHIVA‐guidelines/
- 16.Smith D E, Walker B D, Cooper D A.et al Is antiretroviral treatment of primary HIV infection clinically justified on the basis of current evidence? AIDS 200418709–718. [DOI] [PubMed] [Google Scholar]
- 17.Meersseman W, Van Laethem K, Lagrou K.et al Fatal brain necrosis in primary HIV infection. Lancet 2005366866. [DOI] [PubMed] [Google Scholar]
- 18.Niu M T, Stein D S, Schnittman S M. Primary human immunodeficiency virus type 1 infection: review of pathogenesis and early treatment intervention in humans and animal retrovirus infections. J Infect Dis 19931681490–501 Review.. [DOI] [PubMed] [Google Scholar]
- 19.Kaufmann D, Lichterfeld M, Altfeld M.et al Limited durability of viral control following treated acute HIV infection. Plos Med 20041e36. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Fox J, Scriba T, Oxenius A.et al HIV‐specific immune responses fail to predict CD4 decline or clinical outcome following treatment at primary HIV‐1 infection. Abstract No I‐106. The 13th Conference on Retroviruses and Opportunistic infections 2006
- 21.Quinn T C, Wawer M J, Sewankambo N.et al Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med 2000342921–929. [DOI] [PubMed] [Google Scholar]
- 22.Wawer M J, Gray R H, Sewankambo N K.et al Rates of HIV‐1 transmission per coital act, by stage of HIV‐1 infection, in Rakai, Uganda. J Infect Dis 20051911403–9. Epub 2005 Mar 30. [DOI] [PubMed] [Google Scholar]
- 23.Koopman J S, Jacquez J A, Welch G W.et al The role of early HIV infection in the spread of HIV through populations. J Acquir Immune Defic Syndr Hum Retrovirol 199714249–258. [DOI] [PubMed] [Google Scholar]
- 24.Fox J, McClure M, Weber J.et al Risk factors for the acquisition of HIV in individuals known to have recently seroconverted. BHIVA Conf 2005 Apr 20–2311O15 [Google Scholar]