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The past 2 years have seen a dramatic improvement in the prognosis for people with HIV infection owing to the success of a strategy of using a combination of antiretroviral drugs to bring about a profound and durable suppression of viral replication. The drugs currently available all work through inhibiting key HIV specific enzymes—reverse transcriptase and HIV protease. The use of a three drug cocktail, usually consisting of two reverse transcriptase inhibitors (RTI) and one protease inhibitor (PI), has shown itself to be superior to single1 and dual2 3 drug therapy in terms of the degree of viral suppression and also the ability to stall the development of resistance.4-7
HIV damages the immune system primarily by promoting the destruction of CD4 T lymphocytes, and this leaves the individual vulnerable to a greater number of infections as the cell numbers decline. Following the instigation of triple combination, highly active antiretroviral therapy, often called “HAART”, most recipients experience a rise in blood CD4 T cell numbers, initially in the first month as a result of a release of cells from the reticuloendothelial system, and thereafter because of the production of new cells.8 9 This rise may occur even in people with quite advanced HIV related immunodeficiency and low CD4 counts. A reduction in the number of opportunistic infections,10 11 including cytomegalovirus (CMV) retinitis,12 13 a reduction in the number of hospital admissions,14 and an improvement in the length15 and quality of life have all been shown to occur in the majority of recipients of HAART. Walsh et al have recently shown a dramatic increase in survival of AIDS patients with CMV retinitis who were treated with HAART.16
Before the era of combination antiretroviral therapy, most serious infections with CMV in HIV infected individuals occurred only once the CD4 T lymphocyte count fell below 100×106/l. Clearly, with the use of combination therapy in those whose CD4 count never falls below 100, there should be no risk of CMV. Those who start combination therapy with CD4 counts below 100×106/l may be vulnerable to CMV disease until their immune system recovers sufficiently. When the point of immunocompetence to CMV is regained is something we are unable to measure at present. This is of even more significance in those AIDS patients with existing CMV disease who start HAART and experience an improvement in immune function that may at some point make it unnecessary for them to continue maintenance anti-CMV treatment (which is often toxic, inconvenient, and expensive).17 18
Van den Horn et al report in this issue ofBJO (p 988) on 15 patients with AIDS related CMV retinitis, who were receiving maintenance therapy with anti-CMV drugs, and who, as would be expected, had very low CD4 T lymphocyte counts. They document the recurrence rate of CMV retinitis in these patients after receiving combination therapy including a protease inhibitor. Recurrences occurred in seven patients all of whom had failed to achieve a rise in their CD4 lymphocyte count above 100×106/l. Those patients who successfully obtained CD4 counts above 100×106/l did not suffer any recurrence of CMV retinitis, and one might speculate that it may be safe for those individuals to stop maintenance anti-CMV therapy.
Paradoxically, the improvement in immune function that follows the instigation of HAART may have its drawbacks. Some patients with CD4 T lymphocyte counts below 50–100×106/l may have hitherto unrecognised and asymptomatic infection with CMV retinitis. As immune function returns, so there is an increased inflammatory response which, in the case of CMV retinitis, results in visual loss and an abnormal funduscopic appearance, often quite different from the classic “pizza pie” or “ketchup and scrambled egg” appearances of CMV retinitis.19 20
The practice of the ophthalmologist looking after people with HIV has changed. The widespread use of HAART has reduced the incidence of CMV retinitis and indeed other opportunistic infections of the eye.21 The enhanced immune function that follows the commencement of HAART may produce unexpected appearances of retinitis with severe inflammation.22 Anti-CMV maintenance therapy may now be necessary only for a few months until immune restoration has occurred,23 but specific tests to gauge an individual’s cell mediated immune function against CMV would be useful to tell when this time has been reached. Additionally, some of the drugs used in the HAART combination may have ophthalmic side effects.
One fear is that the effects of HAART will be temporary, lasting perhaps only a few years, after which we may see CMV retinitis and other opportunistic infections becoming commonplace again.
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