HIV Seropositivity: Phillips A

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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Ewings FM, Bhaskaran K, McLean K, Hawkins D, Fisher M, Fidler S, Gilson R, Nock D, Brettle R, Johnson M, Phillips A, Porter K, Anonymous00018. · MRC Clinical Trials Unit, London, UK. · AIDS. · Pubmed #18090396 No free full text.

Abstract: OBJECTIVES: To estimate changes over calendar time in survival following HIV seroconversion in the era of HAART and to provide updated survival estimates. METHODS: Using data from a UK cohort of persons with well estimated dates of HIV seroconversion, we analysed time from seroconversion to death from any cause using Cox models, adjusted for prognostic factors. Kaplan-Meier methods were then used to determine the expected survival in each calendar period. RESULTS: 2275 seroconverters were included with 18 695 person-years of follow up. A total of 444 (20%) died. The relative risk of death, compared with pre-1996, decreased over time to 0.63 [95% confidence interval (CI), 0.48-0.81], 0.24 (0.17-0.34), 0.14 (0.10-0.21), 0.08 (0.05-0.13) and 0.03 (0.02-0.06) in 1996-1997, 1998-1999, 2000-2001, 2002-2003 and 2004-2006, respectively. An elevated risk of death was associated with older age at seroconversion [hazard ratio (HR), 1.49; 95% CI, 1.34-1.66 per 10-year increase] and HIV infection through injecting drug use (HR, 1.53; 95% CI, 1.17-2.00). In 2000-2006, the proportion of individuals expected to survive 5, 10 and 15 years following seroconversion was 99%, 94% and 89%, respectively. CONCLUSIONS: Survival following HIV seroconversion has continued to improve over calendar time in our cohort, even in the more recent years of HAART availability. HIV seroconverters, by definition identified early in their infection, are likely to have the greatest opportunity for intervention; if similar high survival expectations are to be seen in the wider HIV-infected population, early diagnosis is likely to be crucial.

Bhaskaran K, Mussini C, Antinori A, Walker AS, Dorrucci M, Sabin C, Phillips A, Porter K, Anonymous00220. · Medical Research Council Clinical Trials Unit, London, United Kingdom. · Ann Neurol. · Pubmed #17894380 No free full text.

Abstract: OBJECTIVE: Though effective anti-human immunodeficiency virus (HIV) therapies are now available, they have variable penetration into the brain. We therefore aimed to assess changes over calendar time in the risk for HIV-associated dementia (HIV-D), and factors associated with HIV-D risk. METHODS: Using Concerted Action on Seroconversion to AIDS and Death in Europe (CASCADE) data, we analyzed factors associated with time from HIV seroconversion to HIV-D using Cox models with time-updated covariates. The effect of duration of infection was explored using flexible parametric survival models. RESULTS: 222 of 15,380 seroconverters developed HIV-D. The incidence per 1,000 person-years was 6.49 pre-1997 (before highly active antiretroviral therapy was available), declining to 0.66 by 2003 to 2006. Compared with most recent CD4 count > or = 350 cells/mm3, the adjusted relative risk (95% confidence interval) of HIV-D was 3.47 (1.91-6.28), 10.19 (5.72-18.15), and 39.03 (22.96-66.36) at 200 to 349, 100 to 199, and 0 to 99 cells/mm3, respectively. In 2003 to 2006, older age at seroconversion (relative risk = 3.24 per 10-year increase [95% confidence interval, 2.00-5.24]) and previous acquired immune deficiency syndrome diagnosis (relative risk = 4.92 [95% confidence interval, 1.43-16.92]) were associated with HIV-D risk, independently of current CD4 count. HIV-D risk appeared to increase during chronic infection, by 48% at 10 years after seroconversion compared with the lowest risk at 1.8 years. INTERPRETATION: HIV-D incidence has reduced markedly since 1997. However, patients with low (<200 cells/mm3) or even intermediate (200-349 cells/mm3) CD4 counts, previous acquired immune deficiency syndrome diagnosis, longer HIV infection duration, and older age at seroconversion are at increased risk and should be closely monitored for neurocognitive disorders.

Chawla A, Murphy G, Donnelly C, Booth CL, Johnson M, Parry JV, Phillips A, Geretti AM. · Department of Virology, Royal Free Hospital, Royal Free and University College Medical School, London, UK. · J Clin Microbiol. · Pubmed #17151211 links to  free full text

Abstract: A guanidine-based antibody avidity assay for the identification of recently acquired human immunodeficiency virus type 1 (HIV-1) infection was evaluated. The kinetics of maturation of antibody avidity were determined prospectively in 23 persons undergoing acute seroconversion followed for up to 1,075 days. Avidity indices (AI) of <or=0.75 and <or=0.80 reproducibly identified seroconversion within the previous 125 (95% confidence interval [CI], 85 to 164) and 142 (95% CI, 101 to 183) days, respectively. To validate the assay, 432 serum samples from newly diagnosed patients were tested by both the avidity assay and the detuned assay. Results were highly concordant (kappa value for agreement, 0.85). The avidity assay was subsequently used to screen 134 consecutive newly diagnosed patients, including 55/134 (41%) infected with non-B subtypes (A, C, D, G, CRF01, CRF02, CRF06, CRF13, and CRF16). In this cohort, 25/79 (32%) persons with the B subtype and 7/55 (13%) with non-B subtypes showed an AI of <or=0.75, and there were 16/25 (64%) and 3/7 (43%) persons, respectively, with a documented history of acute seroconversion illness within the predicted seroconversion interval. An AI of <or=0.75 was also observed for four patients (three with the B subtype and one with a non-B subtype) who presented with AIDS-defining conditions. In multivariate analysis, an AI of <or=0.75 was associated with younger age, higher HIV-1 plasma RNA load, and being born in the United Kingdom or Ireland rather than in Africa but not with gender, ethnicity, risk group, HIV-1 subtype, or CD4 counts. In conclusion, HIV antibody avidity testing provides a reliable method for identifying recently acquired HIV-1 infection. Results are affected by advanced disease and should therefore be interpreted in the context of other clinical parameters.