Influence of highly active antiretroviral therapy on the development of CMV disease in HIV positive patients at high risk for CMV disease

Background/aims-In the pre-HAART era, HIV positive patients with CD4+ cell counts below 50 cells x10(6)/l, and those with detectable cytomegalovirus ( CA IV) DNA in their peripheral blood, were considered to be at high risk fo r the development of CMV disease. With the start of highly active antiretro viral therapy (HAART), a restoration of immune function occurred in these p atients, and as a consequence patients became less vulnerable to CMV diseas e. Since it is not exactly known how HAART influences CMV viral load in per ipheral blood and the incidence of CMV disease in high risk HIV positive pa tients a group of patients was followed before and after initiation of HAAR T. Methods-29 HIV positive patients, seen in the first 3 months of 1996 at the AIDS clinic of the Academic Medical Centre, at high risk for development o f CMV disease (positive CMV DNA assay in blood and/or CD4+ cell count below 50 cells x10(6)/l), not receiving anti-CMV maintenance therapy, were inclu ded in a prospective cohort study. HAART was started in the second trimeste r of 1996. Patients were evaluated for the occurrence of CMV retinitis, or CMV disease elsewhere, comparing the incidence of CMV events before and aft er the start of HAART. Following the introduction of HAART, CD4+ cell count s and quantitative polymerase chain reaction (PCR) for CMV DNA in blood wer e monitored in all patients who remained alive and were not receiving anti- CMV maintenance therapy (n=22). Follow up was performed until August 1998; the mean follow up after the start of HAART was 14.9 months (range 8-22 mon ths). Results-In the pre-HAART period four patients developed CMV disease, and fo ur died (without clinically manifest CMV disease). After the start of HAART no patient developed CMV disease or died. With HAART, the mean CD4+ cell c ounts increased from 34 cells x10(6)/l to 194 cells x10(6)/l at the end of follow up. CMV DNA could be detected in the blood of 11 patients. Quantific ation showed a decline in the amount of detectable DNA during follow up. At the last examination only one patient showed a positive PCR assay. This wa s the only patient with a CD4+ cell count remaining below 100 cells x10(6)/ l. Conclusion-In HIV positive patients at high risk of CMV retinitis, either w ith a positive CMV PCR assay in blood and/or with CD4+ cell counts below 50 cell x10(6)/l, HAART causes a dramatic decrease in the occurrence of CMV d isease. This decrease is paralleled by an increase in CD4+ cell count, and a decrease in the amount of CMV DNA in the blood, which was below detection levels in all patients with CD4+ cell counts above 100 cells x10(6)/l.