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      Impact of gender on response to highly active antiretroviral therapy in HIV-1 infected patients: a nationwide population-based cohort study

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          Abstract

          Background

          Impact of gender on time to initiation, response to and risk of modification of highly active antiretroviral therapy (HAART) in HIV-1 infected individuals is still controversial.

          Methods

          From a nationwide cohort of Danish HIV infected individuals we identified all heterosexually infected women (N=587) and heterosexually infected men (N=583) with no record of Hepatitis C infection diagnosed with HIV after 1 January 1997. Among these subjects, 473 women (81%) and 435 men (75%) initiated HAART from 1 January 1997 to 31 December 2009. We used Cox regression to calculate hazard ratio (HR) for time to initiation of HAART, Poisson regression to assess incidence rate ratios (IRR) of risk of treatment modification the first year, logistic regression to estimate differences in the proportion with an undetectable viral load, and linear regression to detect differences in CD4 count at year 1, 3 and 6 after start of HAART.

          Results

          At initiation of HAART, women were younger, predominantly of Black ethnicity and had a higher CD4 count (adjusted p=0.026) and lower viral load (adjusted p=0.0003). When repeating the analysis excluding pregnant women no difference was seen in CD4 counts (adjusted p=0.21). We observed no delay in time to initiation of HAART in women compared to men (HR 0.91, 95% CI 0.79-1.06). There were no gender differences in risk of treatment modification of the original HAART regimen during the first year of therapy for either toxicity (IRR 0.97 95% CI 0.66-1.44) or other/unknown reasons (IRR 1.18 95% CI 0.76-1.82). Finally, CD4 counts and the risk of having a detectable viral load at 1, 3 and 6 years did not differ between genders.

          Conclusions

          In a setting with free access to healthcare and HAART, gender does neither affect time from eligibility to HAART, modification of therapy nor virological and immunological response to HAART. Differences observed between genders are mainly attributable to initiation of HAART in pregnant women.

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          Most cited references 45

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          Decline in the AIDS and death rates in the EuroSIDA study: an observational study.

           O Kirk,  A Mocroft,  B Knysz (2003)
          Since the introduction of highly active antiretroviral therapy (HAART), little is known about whether changes in HIV-1 mortality and morbidity rates have been sustained. We aimed to assess possible changes in these rates across Europe. We analysed data for 9803 patients in 70 European HIV centres including ones in Israel and Argentina. Incidence rates of AIDS or death were calculated for overall and most recent CD4 count in 6-monthly periods and in three treatment eras (pre-HAART, 1994-1995; early-HAART, 1996-1997; and late-HAART, 1998-2002). The incidence of AIDS or death fell after September, 1998, by 8% per 6-month period (rate ratio 0.92, 95% CI 0.88-0.95, p<0.0001). When AIDS and death were analysed separately, the incidence of all deaths during the late-HAART era was significantly lower than that during the early-HAART era in patients whose latest CD4 count was 20 cells/microL or less (0.43, 0.35-0.53, p<0.0001), but at higher CD4 counts, did not differ between early-HAART and late-HAART. Incidence of AIDS was about 50% lower in late-HAART than in early-HAART, irrespective of latest CD4 count (p<0.0001). In multivariate Cox's models, with early-HAART as the reference, there was an increased risk of AIDS (relative hazard 1.39; 95% CI 1.16-1.67, p=0.0004) and all deaths (1.29; 1.08-1.56, p=0.0065) in the pre-HAART era, and a reduced risk of AIDS (0.62; 0.50-0.77, p<0.0001) and all deaths (0.66; 0.53-0.82, p=0.0002) in the late-HAART era. The initial drop in mortality and morbidity after the introduction of HAART has been sustained. Potential long-term adverse effects associated with HAART have not altered its effectiveness in treating AIDS.
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            Survival of persons with and without HIV infection in Denmark, 1995-2005.

            The expected survival of HIV-infected patients is of major public health interest. To estimate survival time and age-specific mortality rates of an HIV-infected population compared with that of the general population. Population-based cohort study. All HIV-infected persons receiving care in Denmark from 1995 to 2005. Each member of the nationwide Danish HIV Cohort Study was matched with as many as 99 persons from the general population according to sex, date of birth, and municipality of residence. The authors computed Kaplan-Meier life tables with age as the time scale to estimate survival from age 25 years. Patients with HIV infection and corresponding persons from the general population were observed from the date of the patient's HIV diagnosis until death, emigration, or 1 May 2005. 3990 HIV-infected patients and 379,872 persons from the general population were included in the study, yielding 22,744 (median, 5.8 y/person) and 2,689,287 (median, 8.4 years/person) person-years of observation. Three percent of participants were lost to follow-up. From age 25 years, the median survival was 19.9 years (95% CI, 18.5 to 21.3) among patients with HIV infection and 51.1 years (CI, 50.9 to 51.5) among the general population. For HIV-infected patients, survival increased to 32.5 years (CI, 29.4 to 34.7) during the 2000 to 2005 period. In the subgroup that excluded persons with known hepatitis C coinfection (16%), median survival was 38.9 years (CI, 35.4 to 40.1) during this same period. The relative mortality rates for patients with HIV infection compared with those for the general population decreased with increasing age, whereas the excess mortality rate increased with increasing age. The observed mortality rates are assumed to apply beyond the current maximum observation time of 10 years. The estimated median survival is more than 35 years for a young person diagnosed with HIV infection in the late highly active antiretroviral therapy era. However, an ongoing effort is still needed to further reduce mortality rates for these persons compared with the general population.
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              Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D Study.

              To investigate any emerging trends in causes of death amongst HIV-positive individuals in the current cART era, and to investigate the factors associated with each specific cause of death. An observational multicentre cohort study. All HIV-positive individuals included in one of the cohorts in the Data Collection on Adverse Events of Anti-HIV drugs (D:A:D) Study were included. The association between HIV-specific and non HIV-specific risk factors and death were studied using multivariable Poisson regression. We observed 2482 deaths in 180,176 person-years (PY) on 33,308 individuals [rate/1000 PY = 13.8 (95% CI 13.2-14.3)]. Primary causes of death were: AIDS (n = 743; rate/1000 PY = 4.12), liver-related (341; 1.89), CVD-related (289; 1.60), non-AIDS malignancy (286; 1.59). The overall rate of death fell from 16.9 in 1999/2000 to 9.6/ 1000 PY in 2007/2008. Smoking was associated with CVD and non-AIDS cancers, HBV and HCV co-infection with liver-related deaths, and hypertension with liver-related and CVD deaths. Diabetes was a risk factor for all specific causes of death except non-AIDS cancers, and higher current HIV RNA for AIDS-related deaths. Lower CD4 cell counts were associated with a higher risk of death from all specific causes of death. Multiple potentially modifiable traditional and HIV-specific risk factors for death of HIV-infected persons were identified. The maximum reduction in mortality in HIV-infected populations will require that each of these factors be appropriately addressed. No trends in terms of emerging causes of unexpected deaths were observed, although monitoring will continue.
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                Author and article information

                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central
                1471-2334
                2012
                12 November 2012
                : 12
                : 293
                Affiliations
                [1 ]Department of Infectious Diseases, Hvidovre, Copenhagen University Hospital, Kettegaards Allé 30, Hvidovre DK-2650, Denmark
                [2 ]Clinical Research Center, Hvidovre, Copenhagen University Hospital, Copenhagen, Denmark
                [3 ]Department of Infectious Diseases, Skejby, Aarhus University Hospital, Aarhus, Denmark
                [4 ]Department of Infectious Diseases, Odense University Hospital, Odense, Denmark
                [5 ]Department of Infectious Diseases, The National University Hospital, Rigshospitalet, Copenhagen, Denmark
                [6 ]Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
                1471-2334-12-293
                10.1186/1471-2334-12-293
                3532129
                23140254
                Copyright ©2012 Thorsteinsson et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Research Article

                Infectious disease & Microbiology

                modification, haart, viral suppression, gender differences, hiv

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