HIV Seropositivity: Babiker 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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Porter K, Babiker A, Bhaskaran K, Darbyshire J, Pezzotti P, Porter K, Walker AS, Anonymous00199. · Clinical Trials Unit, 222 Euston Road, , London NW1 2DA, UK. · Lancet. · Pubmed #14575971 No free full text.

Abstract: BACKGROUND: Highly active antiretroviral therapy (HAART) was introduced in 1997. We aimed to assess the continuing effect of this treatment on survival and progression to AIDS after HIV-1 seroconversion. METHODS: We used Cox models to estimate the effect of calendar year on time to AIDS and death in 22 cohorts of people from Europe, Australia, and Canada who had seroconverted. Retrospective and prospective data were used. We compared the effects of age at seroconversion, exposure category, sex, and presentation during acute HIV-1 infection pre-1997 (pre-HAART), in 1997-98 (limited use of HAART), and 1999-2001 (widespread use of HAART). FINDINGS: Of 7740 seroconverters, 2000 (26%) had died. Compared with pre-1997 data, the hazard ratio (HR) for death fell sharply to 0.47 [95% CI 0.39-0.56] in 1997, dropping further to 0.16 [0.12-0.22] in 2001. Correspondingly, the proportion of person-time on HAART increased from 22% in 1997 to 57% in 2001. By contrast with the pre-HAART era, injecting drug users had significantly higher mortality in 1999-2001 than did men infected through sex with men (HR 4.28 [2.86-6.41]). However, whereas pre-1997 the risk of AIDS was higher in those aged 45 years or older at seroconversion than in people who were 16-24 years (2.03 [1.67-2.47]), in 1999-2001 there was little evidence of a difference in risk by age (HR=1.17 [0.60-2.30]; interaction p=0.06). No such attenuation in the effect of age on survival was observed (p=0.63). INTERPRETATION: Predicted survival for people with HIV-1 has continued to increase, since the introduction of HAART; however, the importance of age and exposure category as determinants of progression seems to have changed.

Babiker A, Darbyshire J, Pezzotti P, Porter K, Prins M, Sabin C, Walker AS, Anonymous00066. · MRC Clinical Trials Unit, London, United Kingdom. · J Acquir Immune Defic Syndr. · Pubmed #12626891 No free full text.

Abstract: The effect of HIV infection duration and CD4 cell count on short-term CD4 response was evaluated in treatment-naive seroconverters using logistic regression adjusted for CD4 count before highly active antiretroviral therapy (HAART) as well as for exposure category, age, sex, acute infection, and cohort. This association was also investigated in pretreated seroconverters, further adjusting for prior therapy. CD4 response (increase of >100 cells/microL at 6 months) was more likely if HAART was initiated in the first year following seroconversion (OR = 1.50 [95% CI: 1.07-2.10] compared with 2-5 years). There was no improvement in response from initiating HAART with CD4 count >350 cells/microL compared with 201 to 350 cells/microL. Below 200 cells/microL, however, the chance of a CD4 response appeared to be reduced (OR = 0.72 [95% CI: 0.40-1.28] for 0-200 cells/microL compared with 201-350 cells/microL, P = 0.26). Results were similar for pretreated individuals. Further, in pretreated individuals, a CD4 response was less likely if the CD4 nadir was lower than the pre-HAART CD4 count (OR = 0.18 [95% CI: 0.10-0.36] for >150 cells/microL difference between nadir and pre-HAART CD4 count vs. no difference, P < 0.001). Given the limitations of observational studies, particularly the inability to control for unmeasured confounders, these findings suggest that the initiation of HAART within the first year following seroconversion appears to improve short-term immunologic response. After that time, there is little to be gained in terms of short-term response from initiating HAART before reaching a CD4 count of 200 cells/microL.

Babiker A, Darbyshire J, Pezzotti P, Porter K, Rezza G, Walker SA, Beral V, Coutinho R, Del Amo J, Gill N, Lee C, Meyer L, Tyrer F, Dabis F, Thiebaut R, Lawson-Aye S, Boufassa F, Hamouda O, Fischer K, Pezzotti P, Rezza G, Touloumi G, Hatzakis A, Karafoulidou A, Katsarou O, Brettle R, del Romero J, Prins M, van Benthem B, Kirk O, Pederson C, Hernández Aguado I, Pérez-Hoyos S, Eskild A, Bruun JN, Sannes M, Sabin C, Lee C, Johnson AM, Phillips AN, Francioli P, Vanhems P, Egger M, Rickenbach M, Cooper D, Kaldor J, Ashton L, Vizzard J, Muga R, Day NE, De Angelis D, Anonymous00213. · No affiliation provided · Int J Epidemiol. · Pubmed #12435766 links to  free full text

Abstract: BACKGROUND: Although studies have reported large reductions in the risks of AIDS and death since the introduction of potent anti-retroviral therapies, few have evaluated whether this has been similar for all AIDS-defining diseases. We wished to evaluate changes over time in the risk of specific AIDS-defining diseases, as first events, using data from individuals with known dates of HIV seroconversion. METHODS: Using a competing risks proportional hazards model on pooled data from 20 cohorts (CASCADE), we evaluated time from HIV seroconversion to each first AIDS-defining disease (16 groups) and to death without AIDS for four calendar periods, adjusting for exposure category, age, sex, acute infection, and stratifying by cohort. We compared results to those obtained from a cause-specific hazards model. RESULTS: Of 6,941, 2,021 (29%) developed AIDS and 437 (6%) died without AIDS. The risk of AIDS or death remained constant to 1996 then reduced; relative hazard = 0.89 (95% CI: 0.77-1.03); 0.90 (95% CI: 0.81-1.01); and 0.32 (95% CI: 0.28-0.37) for 1979-1990, 1991-1993, and 1997-2001, respectively, compared to 1994-1996. Significant risk reductions in 1997-2001 were observed in all but two AIDS-defining groups and death without AIDS in a competing risks model (with similar results from a cause-specific model). There was significant heterogeneity in the risk reduction across events; from 96% for cryptosporidiosis, to 17% for death without AIDS (P < 0.0001). CONCLUSION: These findings suggest that studies reporting a stable trend for particular AIDS diseases over the period 1979-2001 may not have accounted for the competing risks among other events or lack the power to detect smaller trends.