| HIGHLIGHTS FROM HAMBURG CMV
Effect of HAART
The implications of highly active antiretroviral therapy (HAART) for the management of
CMV disease in HIV-infected individuals was discussed in one of the parallel sessions this
afternoon. Dr S Matheron (France) presented data from a retrospective analysis comparing
the incidence and characteristics of CMV retinitis in 2 French hospitals from March 1995
to February 1996 (before the introduction of PIs) and from March 1996 to February 1997
(after the introduction of PIs). The introduction of PIs was associated with a lower
incidence of CMV retinitis with 8/338 (2.4%) patients experiencing a first episode of CMV
retinitis compared with 44/488 (9%) patients during the earlier period. Interestingly,
during the second period, CD4 count was >100 cells/mm3 in 4/21 patients who
developed a first episode of retinitis or a relapse. Based on the available data, Dr
Matheron would not recommend discontinuation of anti-CMV therapy in patients treated with
HAART.
The use of PI-containing regimens was also reported to have
a beneficial effect on survival in AIDS patients with CMV retinitis according to a
retrospective case record analysis of 147 patients diagnosed with CMV retinitis between
December 1992 and May 1996 (Dr J Walsh, UK). Between December 1992 and December 1994 the
median survival of patients remained unchanged at 214 days but had increased to 720 days
by May 1996 (p<0.001). Mean survival was markedly increased in those patients who had
received PI therapy compared to those who had not (914 vs 260 days, p<0.0001).
Multivariate analysis by the Cox regression method found that exposure to a PI was an
independent predictor of increased survival (p<0.0001).
Treatment of CMV disease
An intravitreal implant of ganciclovir has been shown to be effective for the local
treatment of CMV retinitis. However, it does not treat or prevent the systemic
manifestations of CMV infections. In the latebreaker poster sessions, Dr D Martin (USA)
presented data from a randomised study evaluating the safety and efficacy of oral
ganciclovir 4.5 g/day for the prevention of new CMV disease (manifest as contralateral
retinitis or extraocular CMV disease) in patients treated with a ganciclovir implant.
Between May 1994 and July 1996, 377 patients with unilateral retinitis were enrolled and
randomised to receive an intravitreal ganciclovir implant plus either placebo or
ganciclovir 1.5g tid, or IV ganciclovir alone (standard induction and maintenance).
Compared with patients treated with the implant alone, patients receiving concomitant oral
ganciclovir had a significantly lower incidence of biopsy proven extraocular disease or
photographically or funduscopically confirmed contralateral CMV retinitis at 6 months
(24.3 vs 44.3%, p<0.002) and a significantly longer time to development of new CMV
disease (p=0.021). Importantly, concomitant use of oral ganciclovir was also associated
with a significant reduction in the incidence of Kaposis Sarcoma (2.7 vs 11.3% in
the implant alone arm, p=0.008). Ganciclovir is known to have in vitro activity
against HHV8, the putative cause of Kaposis Sarcoma. Adverse events were similar
across the treatment arms except for neutropenia which occurred more frequently in the
oral ganciclovir arm and sepsis which occurred more frequently in the IV group.
Dr B. Anduze-Faris (France) discussed the use of a
combination of foscarnet and ganciclovir for acute and maintenance therapy of CMV
encephalitis and myelitus in 31 patients with acute clinical symptoms and 2 positive CSF
CMV PCR results. 27 (74%) patients experienced improvement or stabilisation during
induction (acute) treatment and went on to receive lower maintenance doses of the 2
agents. Survival rates at 2, 6 and 12 months were 74%, 19% and 15%, respectively.
Cidofovir: balancing activity with safety
A poster discussion on Monday evening focused on the safety profile of cidofovir. A
safety update on 408 patients treated with cidofovir between March 1996 and June 1997 in a
named patient supply program was presented by Dr R. Piadino (Italy). At the June 12 cut
off, 165 (40%) patients had discontinued therapy, 42 (10%) for reasons of toxicity.
Toxicities leading to discontinuation included alteration of renal function (6.6%),
haematological toxicity (2%), intolerance to probenecid (1.4%) and uveitis (0.4%). The
overall incidence of uveitis was 4.8%
The incidence of ophthalmologic side effects with
intravenous cidofovir was examined in a prospective study of 9 patients (15 eyes)
receiving cidofovir maintenance therapy for 1 to 9 months. After a period of 2 months, 4
eyes showed iritis, an increasingly well recognised adverse effect of this agent.
Hypotonia (intraocular pressure <10 mmHg) was found in 3 of the 4 eyes. Dr C.
Rosenkranz (Germany) added that, although these events may endanger vision, use of
additional agents such as topical steroids minimize local risks to the eyes.
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