Original papers QJM Passive transfer of scrub typhus plasma to patients with AIDS: a descriptive clinical study G. WATT, P. KANTIPONG 1 , K. JONGSAKUL, M. DE SOUZA and T. BURNOUF 2 From the Retrovirology Department, USAMC, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand, 1 Chiangrai Regional Hospital, Chiangrai, Thailand, and 2 Human Plasma Product Services, Lille, France Received 3 July 2001 and in revised form 24 August 2001 Summary We examined the HIV-inhibitory effects previously found to be associated with scrub typhus infection. Individual 500 ml units of plasma from donors with mild scrub typhus were safety-tested, subjected to virucidal heat treatment, and administered to 10 HIV-1-infected recipients who were not receiving antiretroviral drugs. HIV-1 copy number fell three- fold or more in two recipients, and virus burden was reduced for 8 weeks in 70% (7/10) of recipi- ents of a single plasma infusion, compared with the mean of three pre-infusion measurements. Scrub typhus donor plasma inhibited HIV-1 in vitro compared with normal human plasma and media controls. In the clearest in vivo response, reduc- tion in viral load was accompanied by clinical improvement, a switchback from the syncytia- inducing to the non-syncytia-inducing phenotype, and decreases in CD8 cells and IL-6 levels. Scrub typhus infections can generate heat-stable, transferable plasma factors that exert prolonged anti-HIV effects. Whether variability in the results is due to different scrub typhus infections, different HIV infections or different individual responses, is unclear. Introduction Transient rises in HIV viral load have been reported following immune activation by intercurrent infec- tion, 1,2 immunization, 3,4 and even tuberculin skin testing. 5 Unexpectedly, a drop in viral load was observed in some HIV-1-infected individuals not receiving antiretroviral drugs during acute co-infection with scrub typhus, a chigger-borne zoonosis common in rural Asia. Copy number fell to below detectable limits in some patients. 6 Sera from HIV-uninfected scrub typhus patients and sera from mice inoculated with Orientia tsutsugamushi, the causative agent of scrub typhus, inhibited HIV-1 replication in vitro. 6 A sub- stantial reduction of copy number was associated with scrub typhus co-infection in only 40% of HIV-infected subjects, suggesting that circulating HIV-inhibitory substances appear during some, but not all, scrub typhus infections. We passi- vely transferred plasma from individual patients infected with O. tsutsugamushi to individual recipients with AIDS to test this hypothesis. We also sought to obtain information about donor and recipient determinants of HIV inhibition by scrub typhus. ß Association of Physicians 2001 Address correspondence to Dr G. Watt, DTM&H, Retrovirology Department, AFRIMS, APO AP 96546. e-mail: wattgh@thai.amedd.army.mil Q J Med 2001; 94:599–607