Introduction
According to the World Health Organization, the number of people of all ages living with HIV infection in South Africa was 7 million in 2015 which translates to a prevalence of 19.2% amongst individuals aged 15 years and older. The number of new infections reported in South Africa during 2015 was 380 000 with 180 000 deaths attributed to AIDS during the same period.1 More than 3.3
million (48.0%) people living with HIV received highly active antiretroviral therapy (HAART) during 2015 and this appears to be slowly turning the tide against the HIV pandemic in the country.
Despite recent gains in the battle against HIV/AIDS, South Africa remains one of the countries with the highest prevalence of this disease in the world and intermittently an unusual clinical
presentation is encountered that must be shared with clinicians who work with patients living with HIV. HIV-induced uveitis is such a condition.
Case report
A 44 year old male presented to the Eye Clinic at Tygerberg Academic Hospital in Cape Town with a 3 week history of redness and progressive vision loss in his right eye. He had no previous ocular or medical history of note. On examination his uncorrected visual acuity was decreased in both eyes. The right eye read 0.6 and the left eye 0.5 on a decimal Snellen chart. Both eyes showed mild circumcorneal injection and large keratic precipitates on the endothelium (Figure 1a). Inflammatory activity was noted in the anterior chambers and the anterior vitreous humor of both eyes. In both
eyes small fluffy nodules were prominent all along the pupil margin (Figure 1b). The rest of the eye examination was normal. Topical corticosteroid therapy was commenced to address the
inflammation while special investigations were being performed.
Routine first-line investigations were requested to search for the underlying cause of the uveitis. These included a full blood count, erythrocyte sedimentation rate, creatinine, syphilis serology as well as serum angiotensin converting enzyme level and all had negative results. An HIV test was requested after obtaining informed consent. The patient was newly diagnosed with HIV infection with a CD4+ cell count of 121 x 106/L. Chest radiography was normal and dipstick urinalysis revealed
1+ protein only. A tuberculin skin test (17mm) and QuantiFERON-TB Gold test (1.59) were both positive but subsequent high-resolution chest computed tomography (CT) scan was normal making a diagnosis of intraocular tuberculosis unlikely. A 0.1mL sample of aqueous humor (AH) was obtained from the right anterior chamber and tested by multiplex PCR for herpes viruses 1 -6. The qualitative multiplex PCR was positive for Epstein-Barr virus (EBV) although a quantitative PCR showed that the EBV viral load (VL) was lower than the detectable limit and therefore also unlikely to be the cause of the inflammation.
Since the intraocular inflammation was not improving on topical corticosteroid treatment, a second paired AH and blood sample was obtained to determine the HIV VL in the ocular fluid and blood. The HIV VL in the blood was 215 810 copies/mL while the HIV VL in the AH was 35 724 280 copies/mL thereby demonstrating that the virus had been replicating inside the eye. This was regarded as convincing evidence for the diagnosis of HIV-induced uveitis. The patient was commenced on first- line HAART and the inflammation subsided within three weeks without any further corticosteroid treatment and has remained asymptomatic for more than 30 months.
Discussion
It is well known that HIV infection predisposes patients to a wide range of opportunistic infections that may also involve the eye and cause intraocular inflammation.2,3 The notion that HIV infection
per se may also cause intraocular inflammation has been entertained since the late 1980’s but
laboratory evidence to support this hypothesis was lacking for many years and the diagnosis was initially based on a positive response to zidovudine monotherapy.4 In 1998, Rosberger et al cultured
HIV from the AH of 3 eyes and vitreous humor of 1 eye suspected of having HIV-induced uveitis.5 In
2008, Rothova et al demonstrated that a patient with HIV-induced uveitis had an intraocular HIV-1 RNA viral load which was several times higher than that in the plasma thus indicating that HIV can locally replicate inside the eye and cause inflammation.6
Subsequent reports from Thailand helped to elucidate the clinical manifestations characteristic of HIV-induced uveitis.2,7 Kunavisarut et al found that all patients presented with decreased visual
acuity and that none were receiving HAART at the time of diagnosis.2 On clinical examination none of
the patients had conjunctival hyperemia despite all having anterior uveitis with characteristic keratic precipitates on the corneal endothelium. Furthermore, no retinal lesions or scars were noted and no clinical evidence suggestive of opportunistic infections was found. Laboratory investigations also did not provide any evidence of opportunistic infections and in all cases the intraocular HIV load was found to be much higher than the plasma HIV load although in some instances the inflammation was present for 2 years before the diagnosis was confirmed. None of the patients responded to topical and/or systemic corticosteroid therapy but in all cases complete resolution of the intraocular inflammation occurred after administration of HAART. The case described in this paper therefore matches every aspect of this description but also includes a previously unreported finding of small fluffy nodules along the pupil margin. Interestingly, the patients described in both 1988 and 1998 also show significant similarities to these cases.4,5 The concept of HIV-induced uveitis has therefore
work with patients living with HIV are unaware of this condition. In contrast, most health workers are well aware of the opportunistic ocular infections and inflammation associated with HIV infection. It is therefore important to bring HIV-induced uveitis to the attention of everyone working in the field of HIV medicine in order to ensure that the condition is suspected, diagnosed and treated correctly before any permanent ocular damage occurs.
Legends: Figure 1a: Large keratic precipitates on the corneal endothelium (arrow). Figure 1b: Small fluffy nodules all along the pupil margin (arrows)
References:
1. Joint United Nations Programme on HIV/AIDS (UNAIDS), Joint United Nations Programme on HIV/AIDS (UNAIDS). Global AIDS update 2016. Geneva, Switzerland. 2016.
2. Kunavisarut P, Sirirungsi W, Pathanapitoon K, Rothova A. Clinical manifestations of Human Immunodeficiency Virus-induced uveitis. Ophthalmology. 2012;119(7):1455-1459.
3. London NJS, Shukla DMNAMS, Heiden D, Rathinam SRNMAMS, Arevalo JF, Cunningham ET. HIV/AIDS in the developing world. Int Ophthalmol Clin. 2010;50(2):201-218.
4. Farrell PL, Heinemann MH, Roberts CW, Polsky B, Gold JW, Mamelok A. Response of Human Immunodeficiency Virus-associated uveitis to zidovudine. Am J Ophthalmol. 1988;106(1):7-10.
5. Rosberger DF, Heinemann M, Friedberg DN, Holland GN. Uveitis associated with Human Immunodeficiency Virus infection. Am J Ophthalmol. 1998;125(3):301-305.
6. Rothova A, Schneider M, de Groot-Mijnes JD. Human immunodeficiency virus-induced uveitis: Intraocular and plasma human immunodeficiency virus-1 RNA loads. Ophthalmology.
2008;115(11):2062-2064.
7. Pathanapitoon K, Riemens A, Kongyai N, et al. Intraocular and plasma HIV-1 RNA loads and HIV uveitis. AIDS. 2011;25(1):81-86.
Chapter 8: Original article – Submitted for publication on 1 September 2017 to Ocular Immunology