A case of multidrug resistant primary HIV infection with delayed CD4 T-cell count decline despite low viral load, treated with interleukin-2.
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Publications and source records attributed to David Pao.
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OBJECTIVE: To study primary HIV-1 infections (PHI) using molecular and epidemiological approaches in order to assess correlates of transmission in this population. METHODS: Individuals with PHI were recruited prospectively from a discrete cohort of 1235 individuals under follow-up in a well-defined geographical area between 1999 and 2003. PHI was diagnosed by one of the following: negative HIV antibody test within 18 months, evolving antibody response, or application of the serological testing algorithm for recent HIV seroconversion. The pol gene was sequenced to identify genotypic resistance and facilitate molecular epidemiological analysis. Clinical data were collected and linked in an irretrievable fashion when informed consent was obtained. RESULTS: A total of 103 individuals with PHI diagnosed between 1999 and 2003 were included in the study; 99 (96%) were male and 90 (91%) were men who have sex with men. Viruses from 35 out of 103 (34%) appeared within 15 phylogenetically related clusters. Significant associations with clustering were: young age, high CD4 cell count, number of sexual contacts, and unprotected anal intercourse (UAI) in the 3 months before diagnosis (P < 0.05 for all). High rates of acute sexually transmitted infections (STI) were observed in both groups with a trend towards higher rates in those individuals with viruses within a cluster (42.9 versus 27.9%; P = 0.13). CONCLUSION: High rates of partner change, UAI and STI are factors that facilitate onward transmission during PHI. More active identification of individuals during PHI, the management of STI and highly active antiretroviral therapy may all be useful methods to break transmission networks.
Primary infection with drug-resistant HIV-1 is well documented. We have followed up patients infected with such viruses to determine the stability of resistance-associated mutations. Fourteen patients who experienced primary infection with genotypic evidence of resistance were followed for up to 3 years. Drug resistance-associated mutations persisted over time in most patients studied. In particular, M41L, T69N, K103N, and T215 variants within reverse transcriptase (RT) and multidrug resistance demonstrated little reversion to wild-type virus. By contrast, Y181C and K219Q in RT, occurring alone, disappeared within 25 and 9 months, respectively. Multidrug resistance in 2 patients was found to be stable for up to 18 months, the maximum period studied. We conclude that certain resistance-associated mutations are highly stable and these data support the recommendation that all new HIV diagnoses in areas where primary resistance may occur should undergo genotyping irrespective of whether the date of seroconversion is known.
UNLABELLED: This study was conducted at Centenary Health Centre of the Rouge Valley Health System, a community based hospital in Toronto. In January 1997, a new treatment was introduced for the management of patients with uncomplicated deep vein thrombosis (DVT). Eligible patients presenting at the ER were placed on LMWH (tinzaparin) and followed at home. Previously the patients had been hospitalized and treated with intravenous heparin until they reached a therapeutic international normalized ratio (INR). The intent of this study was to evaluate the patient outcomes and cost-savings of the new approach. METHODS: Data from all patients eligible for home care, treated in 1996 were assembled and compared with those from all eligible patients treated from April 1, 1997 to March 31, 1998. The data was collected by chart review and consisted of patient outcomes and costs during the period of heparin treatment. Costs for hospitalized patients were based on a per diem. For home care patients, the costs were itemized according to service and medication usage. All costs were calculated in 1999 Canadian dollars. RESULTS: In each one year period, 39 cases were treated. There was no serious adversity and the outcomes were compatible with what has been reported in the literature. The mean cost per patient for the 1996 hospitalized cohort was $3,266 compared to $584 for the subsequent home care cohort. The difference was statistically significant (p<0.00001). CONCLUSION: Home care with tinzaparin compared to hospital care with IV heparin resulted in a large mean saving per patient with no difference in outcome.
Syphilis is a sexually transmitted infection which is systemic from the outset and has increased in incidence worldwide over the last decade. There has been concern as to whether or not co-infection with HIV can modify the clinical presentation of syphilis and, as a genital ulcer disease, it can facilitate the transmission of HIV infection. Diagnosis is based on the microscopic identification of the causative treponeme and serological testing. Recommendations for the treatment of syphilis have been based on expert opinion, case series, some clinical trials and 50 years of clinical experience. Penicillin, given intramuscularly, is the mainstay of treatment and the favoured preparations for early infectious syphilis are benzathine penicillin as a single injection or a course of daily procaine penicillin injections for 10 to 14 days. The duration of treatment is longer for late syphilis. There has been concern that benzathine penicillin may not prevent the development of neurosyphilis but that is a rare outcome with this therapy. The main alternative to penicillin is doxycycline, but the place of azithromycin and ceftriaxone is yet to be established. It is not necessary to carry out examination of the cerebrospinal fluid in patients with early infectious syphilis but it should be performed in those with neurological or ocular signs, psychiatric signs or symptoms, when there is evidence of treatment failure and in those who are co-infected with HIV. Follow-up is an essential part of management and should be particularly assiduous, for at least 24 months, in those co-infected with HIV. Partner notification should be mandatory to try to contain the spread of infection.