HIV Seroconversion Illness Update Latest HIV Assays May Still Be Negative
Total Page:16
File Type:pdf, Size:1020Kb
CLINICAL PRACTICE HIV seroconversion illness Update Latest HIV assays may still be negative Human immunodeficiency virus (HIV) seroconversion illness occurs in up to 80% of patients who newly acquire the virus. It is hoped that the new fourth generation HIV assay will have improved sensitivity for diagnosis. This article describes Matthew Shields the case of a patient who presented with typical symptoms of HIV seroconversion illness but who had a negative initial MBBS, FRACGP, DipGUM(Lond), test with the new assay. Current management of HIV seroconversion illness is also outlined. DFFP, is a registrar in sexual health and HIV medicine, Darlinghurst, New South Wales. mdshields@hotmail. com Case study Mr D, a homosexual man aged 34 years, presented with a 3 day history of painful ulcers in the mouth and on the penis associated with high fever and night sweats, malaise, myalgia, headache, and a sore throat. He had unprotected anal intercourse with a HIV positive casual partner 10 days previously. Four days after this casual contact he presented to his general practitioner with a profuse urethral discharge which was diagnosed as urethral gonorrhoea. This responded well to intramuscular ceftriaxone. Mr D was previously very well with no medical problems or allergies and reported a negative HIV test 3 months earlier. On examination he appeared very unwell with a temperature of 380C and mild dehydration. There was no rash. Examination of the mouth revealed tender ulceration of the hard palate (Figure 1) and a diffuse erythematous pharyngitis. Genital examination revealed one large, slightly tender ulcer (1.5 cm) on the shaft of the penis. Inguinal nodes were not enlarged or tender and there was no other lymphadenopathy. The ulcer was deep and without induration. Syphilis and HIV serology were performed and a swab from the penile ulcer was sent for herpes simplex virus (HSV) polymerase chain reaction (PCR). HIV screening utilised a fourth generation assay for combined HIV antibody and p24 antigen detection. The result, available later that day, was negative. The patient was seen 2 days later for clinical review, The patient was counselled appropriately and repeat HIV serology, and full sexually transmitted initiated on a short course of antiretroviral (ARV) infection (STI) screening. He showed improvement therapy that day with lopinavir/ritonavir, tenofovir and systemically but had additional oral discomfort. 3TC.1 Herpes simplex virus PCR from the penile ulcer Examination revealed some additional ulceration was negative. Syphilis serology at presentation and at of the oral labial mucosa as well as the hard palate, weeks 4 and 12 were also negative, excluding syphilis but the penile ulceration was much improved. and indicating genital ulceration was occurring in the Posterior cervical nodes were now palpable bilaterally context of HIV seroconversion. Repeat HIV serology and Mr D had developed a faint pink truncal macular in subsequent weeks revealed evolving reactivity on rash (Figure 2). the western blot, and a viral load taken with symptoms was more than 750 000; both results consistent The repeat fourth generation assay that day was reactive. with seroconversion. Additional tests, including western blot, revealed one Basic blood tests including full blood count (FBC), reactive band (p24) and the isolated p24 antigen assay electrolytes, urea, creatinine (EUC), and liver function (a more specific test) was reactive, confirming HIV tests (LFTs) taken at the initial visit revealed a transient seroconversion illness. thrombocytopaenia and lymphopaenia, and mild hepatitis, Reprinted from Australian Family Physician Vol. 35, No. 7, July 2006 523 CLINICAL PRACTICE HIV seroconversion illness – latest HIV assays may still be negative Other tests are sometimes used for diagnosing seroconversion (eg . PCR). However, HIV RNA PCR (viral load) assays are quantitative tests and cannot be relied upon for diagnosis because of poor specificity in the form of low level false positives.3 Proviral DNA is a HIV DNA PCR test that is more sensitive and more specific than a viral load assay making it a good second line test or Figure 1. Ulceration of the hard palate useful adjunct to the fourth generation assay. Photo courtesy Mark Nelson, The Chelsea and Westminster Hospital, London A proviral DNA requires a whole blood sample. It is important to indicate on the request with LFTs no more that twice the upper limit of form, or telephone the reference laboratory, if normal. Hepatitis B status previously recorded in seroconversion illness is suspected. the notes indicated the patient was a hepatitis B Management of seroconversion illness exposed noncarrier (natural immunity). Pa t i e n t s c o n f i r m e d o r s u s p e c t e d o f Discussion HIV seroconversion illness should be Human immunodeficiency virus seroconversion referred immediately to a HIV specialist Figure 2. Patient displaying truncal macular rash illness (or primary HIV infection) is thought Photo courtesy Mark Nelson, The Chelsea and general practitioner or sexual health to occur in up to 80% of patients who newly Westminster Hospital, London service (Table 1). acquire the virus.2,3 It typically occurs 10–14 days Prompt treatment of confirmed HIV after infection. Symptoms last approximately 1 serology was requested. Syphilis serology seroconversion with a short course of ARV week. Classic symptoms include: is essential in all men who have sex therapy (usually 3–6 months) is an option. This • fever with men presenting with the above syndrome. is not standard of care but is at the discretion • rash of the treating physician and patient. Treating Testing for seroconversion illness • malaise seroconversion illness with a short course of • sore throat, and Experience with third generation (antibody ARV drugs has the potential to slow disease • generalised lymphadenopathy.4,5 only) HIV enzyme immunoassays (EIA) in progression by preserving HIV specific Because these symptoms are transient and recent years suggests these tests become cytotoxic T-lymphocyte responses.9 However, influenza-like, seroconversion illness often goes positive around the time of seroconversion the evidence base is small and it remains an unrecognised by both the patient and doctor. illness. This makes sense because as the name important unanswered study question.10 Other known manifestations are oral and genital suggests, seroconversion illness is the time Further data is expected from SPARTAC, a large ulceration. Potential neurological complications of seroconversion to HIV antibody. Therefore international multicentre trial rolled out last include meningitis, encephalitis, and Guillain these EIAs may be negative on a sample year by St Mary’s Hospital, London, currently Barre syndrome.6 The transient drop in CD4 taken 1 day during the illness but positive on a randomising seroconverters to treatment or not. count that may occur during seroconversion sample taken the following day. Other potential advantages of treating may also push the patient into the realm of well The fourth generation assay (that combines seroconversion include reduction of symptoms known HIV related disease (eg. oral candidiasis p24 antigen) should prove a more sensitive test and reduced risk of HIV transmission. or pneumocystis carinii pneumonia). for HIV seroconversion because p24 antigen Potential disadvantages include toxicity, The differential diagnosis of a febrile illness typically appears 5 days before antibody.7,8 This financial cost, and the potential to foster or with generalised rash and lymphadenopthy test is the same test now used for general potentiate a drug resistant virus. Studies could include: HIV screening by all reference laboratories in indicate that treatment with ARV drugs • HIV seroconversion Australia. requires more than 95% compliance to guard • secondary syphilis Overall the fourth generation combined against developing drug resistance.11 Such • Epstein Barr virus (EBV) antibody/antigen assay is the best first line test compliance could be undermined by the • cytomegalovirus (CMV) for the diagnosis of suspected seroconversion. trauma of the new HIV diagnosis, thereby • acute toxoplasmosis However, as this case suggests, this assay may fostering drug resistant virus. In addition, the • acute hepatitis B, and still be negative with peak symptoms. A repeat transmission of drug resistant virus is a real • rubella.6 sample and test in 2–3 days is recommended entity and such virus can be potentiated by In this patient, however, only HIV and syphilis when there is an index of suspicion. an immediate course of ARV therapy.9 In this 524 Reprinted from Australian Family Physician Vol. 35, No. 7, July 2006 HIV seroconversion illness – latest HIV assays may still be negative CLINICAL PRACTICE but still may initially be negative, necessitating a Table 1. Management algorithm for HIV repeat sample in 2–3 days. Patients confirmed or seroconversion illness suspected of HIV seroconversion illness should Could this be seroconversion illness? be referred immediately to a HIV specialist GP or • Was there a substantial risk sexual health service. (eg. unprotected anal intercourse)? • What is the time course (10–14 Acknowledgment days)? Thanks to Dr Robert Finlayson, TSPC, and Phillip • Are typical symptoms present Cunningham, St Vincent's HIV Lab, Sydney, New (eg. fever, rash, sore throat, malaise, generalised lymphadenopathy)? South Wales. HIV test Conflict of interest: none declared. • Provide patient with pretest counselling References • Indicate suspected seroconversion 1. Fidler S. Comparative potency of three antiretrovi- ral therapy regimens in primary HIV infection. AIDS on the request form, or telephone 2006;20:247–52. the reference laboratory 2. Schacker T, Collier A, Hughes J, et al. Clinical and • Fourth generation assay (ask if same epidemiological features of primary HIV infection. Ann day result is available) Intern Med 1996;125:257–64. • Consider proviral DNA if available 3. Hecht F, Busch M, Rawal B, et al. Use of laboratory tests (requires a whole blood sample) and clinical symptoms to identify primary HIV infection. AIDS 2002;16:1119–29. • Undertake full STI screening 4. Cooper D, Gold J, Maclean P, et al.