HIV Seropositivity: Nelson M

Pozniak A, Gazzard B, Anderson J, Babiker A, Churchill D, Collins S, Fisher M, Johnson M, Khoo S, Leen C, Loveday C, Moyle G, Nelson M, Peter B, Phillips A, Pillay D, Wilkins E, Williams I, Youle M, Anonymous00074. · Chelsea and Westminster Hospital, London, UK. · HIV Med. · Pubmed #14511246 No free full text.

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Low E, Vogel M, Rockstroh J, Nelson M. · Department of Sexual Health and HIV, Chelsea and Westminster Hospital, London, UK. · AIDS Rev. · Pubmed #19092980 No free full text.

Abstract: Due to the asymptomatic nature of acute hepatitis C it can be difficult to diagnose in the early stage of infection, but with the higher treatment success rates and reduced treatment duration at this stage, it is imperative that diagnoses are made. Therefore, physicians should routinely screen at-risk individuals and investigate abnormal liver function tests. Serum HCV RNA should be considered in any HCV-antibody-negative individual in whom acute HCV is clinically suspected, or annually in those high-risk individuals with previous infection. Acute hepatitis C transmission may be facilitated by the presence of an erosive genital lesion, such as syphilis or lymphogranuloma venereum, and thus testing at this time should be encouraged. Reinfection with HCV does occur and patients need to be informed of the sexual and other high-risk behaviors that put them at risk of reinfection. Public awareness of the possibility of HCV infection, and subsequent reinfection, in high-risk groups should be increased. The question of the optimal treatment regimen is still disputed. However, ongoing trials and the proposed randomized controlled trial from the European AIDS Treatment Network should answer many of our questions. In the meantime, units faced with HIV/acute hepatitis C coinfection should follow recommendations from the HCV-HIV International Panel.

Boffito M, Dickinson L, Hill A, Back D, Moyle G, Nelson M, Higgs C, Fletcher C, Mandalia S, Gazzard B, Pozniak A. · Chelsea and Westminster Hospital, London, UK. · Antivir Ther. · Pubmed #15259905 No free full text.

Abstract: OBJECTIVE: To evaluate the steady-state pharmacokinetics and safety of two once-daily saquinavir/ritonavir (SQV/RTV) regimens, 1600/100 and 2000/100 mg, in HIV-positive patients. METHODS: Eighteen HIV-infected adults treated with the standard twice-daily SQV/RTV 1000/100 mg regimen were enrolled in this open-label, two-phase, crossover pharmacokinetic study. The steady-state pharmacokinetics of SQV administered with 100 mg RTV were investigated following once-daily doses of 1600 mg or 2000 mg or a twice-daily dose of 1000 mg. Plasma drug concentrations were determined by high performance liquid chromatography-tandem mass spectrometry and pharmacokinetic parameters were calculated using a non-compartmental model. RESULTS: Compared with SQV 1000 mg twice daily, the Cmax of SQV following a 1600 mg and 2000 mg dose increased in a dose-proportional manner [geometric mean (95% CI) 1915 (1656-2850) ng/ml for 1000 mg, 2782 (2249-4330) ng/ml for 1600 mg and 4179 (3429-6105) ng/ml for 2000 mg doses, respectively]. SQV Ctrough values were 539 (453-1011), 106 (76-223) and 231 (75-822) ng/ml, respectively. A SQV Ctrough value greater than 100 ng/ml was achieved in all subjects on the twice-daily regimen, in 9/18 (50%) subjects on the 1600/100 mg once-daily regimen, and in 14/17 (82%) subjects on the 2000/100 mg once-daily regimen. The once-daily regimens were well tolerated, with mild-to-moderate gastrointestinal symptoms being the only events reported by a small number of patients. CONCLUSION: This is the first study to evaluate the pharmacokinetics of once-daily SQV/RTV 2000/100 mg in HIV-infected subjects. Our findings suggest that this regimen may be an alternative to twice-daily 1000/100 mg doses and should be further evaluated in efficacy studies. The data indicate that most patients (14/17) on once-daily 2000/100 mg achieve trough concentrations above target values (determined for HIV wild-type) for efficacy of SQV with the use of just 100 mg RTV/day and with good tolerability.

van de Laar T, Pybus O, Bruisten S, Brown D, Nelson M, Bhagani S, Vogel M, Baumgarten A, Chaix ML, Fisher M, Gotz H, Matthews GV, Neifer S, White P, Rawlinson W, Pol S, Rockstroh J, Coutinho R, Dore GJ, Dusheiko GM, Danta M. · Cluster of Infectious Diseases, Health Service, Amsterdam, The Netherlands. · Gastroenterology. · Pubmed #19422083 No free full text.

Abstract: BACKGROUND & AIMS: Since 2000, there has been a marked rise in acute hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). We conducted an international phylogenetic study to investigate the existence of an HCV transmission network among MSM. METHODS: HIV-positive MSM diagnosed with recent HCV (n = 226) in England (107), The Netherlands (58), France (12), Germany (25), and Australia (24) between 2000 and 2006 were enrolled into a molecular phylogenetic study. Using real-time polymerase chain reaction (PCR), the NS5B region of the HCV genome (436 base pair) was amplified, sequenced, and compared with unrelated NS5B sequences. RESULTS: NS5B sequences were obtained from 200 (89%) cases. Circulating HCV genotypes were 1a (59%), 4d (23%), 3a (11%), 1b (5%), and 2b/c (3%). Phylogenetic analysis revealed 156 (78%) sequences that formed 11 clusters (bootstrap value > 70%) containing between 4 and 37 individual sequences. Country mixing was associated with larger cluster size (17 vs 4.5 sequences; P = .03). "Molecular clock" analysis indicated that the majority (85%) of transmissions occurred since 1996. CONCLUSIONS: Phylogenetic analysis revealed a large international network of HCV transmission among HIV-positive MSM. The rapid spread of HCV among neighboring countries is supported by the large proportion (74%) of European MSM infected with an HCV strain co-circulating in multiple European countries, the low evolutionary distances among HCV isolates from different countries, and the trend toward increased country mixing with increasing cluster size. Temporally, this epidemic coincides with the introduction of highly active antiretroviral therapy and associated increases in sexual risk behaviors. International collaborative public health efforts are needed to mitigate HCV transmission among this population.

Koh DM, Burn PR, Mathews G, Nelson M, Healy JC. · Chelsea and Westminster Hospital, London, UK. · Can Assoc Radiol J. · Pubmed #12625084 No free full text.

Abstract: OBJECTIVE: To compare the computed tomographic (CT) findings of abdominal Mycobacterium tuberculosis (MTB) infection and Mycobacterium avium intracellulare (MAI) infection in patients with human immunodeficiency virus (HIV) infection. METHODS: A retrospective review of the CT findings of 30 patients with HIV and proven MTB (n = 9) or MAI (n = 21) infection was conducted. Images were reviewed by a radiologist blinded to the diagnosis, and the radiologic findings involving the abdominal viscera, peritoneum and lymph nodes were compared. RESULTS: The following were more frequent in patients with MAI infection: hepatomegaly (MAI 71% v. MTB 44%, p < 0.05), uniform attenuation of lymph nodes (MAI 90% v. MTB 55%, p < 0.05) and clustered pattern of lymph nodes (MAI 57% v. MTB 22%, p < 0.05). In patients with MTB infection, lymph nodes with low attenuation centrally were more common (MAI 10% v. MTB 44%, p < 0.05), and mesenteric lymph nodes were significantly larger (MAI mean = 20 mm v. MTB mean = 40 mm, p < 0.05). CONCLUSION: Although nonspecific, CT may be useful in the early diagnosis of MTB and MAI infection, allowing for presumptive treatment before microbiologic confirmation.

Bower M, Fife K, Sullivan A, Kirk S, Phillips RH, Nelson M, Gazzard BG. · Department of Oncology, Chelsea & Westminster Hospital, London, U.K. · Eur J Cancer. · Pubmed #10492634 No free full text.

Abstract: A retrospective analysis identified 38 HIV seropositive patients with a diagnosis of presumed (n = 26) or confirmed (n = 12) primary cerebral lymphoma (PCNSL). All patients had failed to respond to empirical antitoxoplasma therapy and the clinical diagnosis of PCNSL was confirmed by brain biopsy (n = 4), cerebrospinal fluid (CSF) examination for Epstein-Barr virus (EBV) by PCR (n = 7) or postmortem examination (n = 1). There was no difference in the age, performance status, CD4 counts, antiretroviral usage or interval since first HIV serodiagnosis between patients with presumed or confirmed PCNSL. 16 patients received either radiotherapy (n = 14) or chemotherapy (n = 2). Patients with confirmed or presumptive PCNSL were equally likely to receive treatment. The median overall survival, which was measured from the end of unsuccessful antitoxoplasma therapy, was 1.2 months for the whole cohort. There was no difference in overall survival between patients with presumptive (median 0.8 months) and confirmed (median 1.3 months) PCNSL (logrank P = 0.69). This suggests that there may be little value in positively diagnosing PCNSL in the current diagnostic algorithm. Recent improvements in outcome have been reported with systemic chemotherapy in HIV-PCNSL and may influence the need for earlier definitive diagnosis in the future.