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Biomedical subjects

F Boufassa

Publications and source records attributed to F Boufassa.

14 recordsLinked to original sources

Cytomegalovirus seroconversion as a cofactor for progression to AIDS.

OBJECTIVE: To study the impact of cytomegalovirus (CMV) seroconversion on HIV-1 disease progression. DESIGN: Follow-up of CMV-seronegative subjects enrolled in the French SEROCO/HEMOCO cohorts of HIV-infected subjects. METHODS: A total of 290 subjects were CMV-seronegative at enrolment in the cohort. Serological testing for CMV infection was done at enrolment and then every 6 months in CMV-seronegative subjects. The person-years method was used to calculate the incidence of CMV seroconversion. After adjustment for age, the CD4+ cell count at enrolment and the HIV exposure group in a Cox model, we studied CMV seroconversion as a time-dependent variable in progression to a CD4+ cell count below 200 x 10(6) cells/l and to clinical AIDS. RESULTS: Overall, 61 CMV seroconversions were observed. The overall incidence rate was 4.4 per 100 person-years [95% confidence interval (CI), 3.3-5.5]. The risk of progression to a CD4+ cell count below 200 x 10(6) cells/l was not increased in CMV seroconverters. However, the risk of progression to AIDS was increased two-fold in CMV seroconverters compared with subjects who remained CMV-seronegative [relative risk (RR) = 2.09; 95% CI, 1.16-3.74; P = 0.01]. CONCLUSION: This analysis of 61 CMV seroconversions, the largest study in the literature, confirms the impact of recent CMV infection on progression to AIDS.

AIDS-Related Opportunistic Infections↗

Using phylogenetic analysis to trace HIV-1 migration among western European injecting drug users seroconverting from 1984 to 1997.

OBJECTIVE: To reconstruct the epidemiological relationships of the HIV epidemics among injecting drug users (IDU) in western Europe. METHODS: HIV env V3 sequences of and epidemiological data were obtained from 145 IDU who seroconverted in three sequential periods: 1984-1988, 1989-1992 and 1993-1997. The sequences were phylogenetically analysed and examined for signature patterns characteristic of northern European IDU, including the conserved GGC codon in the V3 loop. RESULTS: Subpopulations of genetically related HIV strains were observed in Italy, France, Scotland and Spain, in contrast to the Netherlands, Austria and Switzerland. This difference between the two groups of countries suggests that the HIV epidemics amongst IDU in the latter group was caused by multiple virus introductions. In Edinburgh and the surrounding area, most IDU were infected with the same GGC strain over the 12-year study period. The epidemic among IDU in north-western Europe started with GGC viruses, whereas in south-western Europe non-GGC viruses predominated. This geographical separation has faded during the course of the epidemic, most likely because of virus exchange among IDU populations.

Base Sequence↗

Sexual behavior changes and protease inhibitor therapy. SEROCO Study Group.

OBJECTIVE: To examine changes in sexual activity and unprotected sexual intercourse among HIV-infected patients before and after the initiation of protease inhibitor therapy. DESIGN: An analysis of data from the SEROCO Study, a French prospective cohort. METHODS: All 191 patients who initiated protease inhibitor therapy after 1 January 1996, who were interviewed within one year before the initiation of therapy (Time 1), and who had at least 6 months of follow-up after therapy initiation (Time 2) were included. Patients provided information about sex partner characteristics and unprotected sexual intercourse. RESULTS: Eighty-one (42%) were gay or bisexual men, 46 (24%) were heterosexual men, and 64 (34%) were women. No significant increases were found in either the number of patients reporting anal or vaginal sex or the number reporting unprotected sexual intercourse after protease inhibitor initiation. However, in matched pair analysis, gay or bisexual men were three times more likely to report having had unprotected sexual intercourse with partners who were of HIV-negative or unknown serostatus after protease inhibitor initiation [relative risk (RR) = 3.0, 95% confidence interval (CI) = 1.2-7.6]. Non-significant decreases in unprotected sexual intercourse among both heterosexual men and women were also observed. No relationship between plasma viral load after protease inhibitor initiation and unprotected sexual intercourse was found in these data. CONCLUSIONS: A relapse in sex risk practices among some HIV-infected gay or bisexual men cannot be ruled out and requires both continued monitoring and immediate secondary preventative intervention.

Adult↗

Is cytomegalovirus infection a co-factor in HIV-1 disease progression?

The influence of cytomegalovirus (CMV) infection as a co-factor in HIV-1 disease progression has mainly been studied in haemophiliacs and remains controversial. Based on the files of 1683 HIV-1-infected patients in the Seropositive Cohort (SEROCO) and Haemophiliacs Cohort (HEMOCO) cohorts, we studied the role of CMV infection in progression to CD4+ cell counts of less than 200 microl, AIDS onset and death, in various HIV exposure groups. Adjusted relative risk (aRR) of progression to AIDS and to death was respectively 1.30 (P = 0.05) and 1.58 (P = 0.007). In the sexual exposure group the influence of CMV infection on the risk of progression to AIDS was of borderline significance (aRR = 1.50; P = 0.07) and was more marked on the risk of death (aRR = 2.00; P = 0.03). No such influence of CMV infection was observed in the transfusion and intravenous drug use exposure groups. When we studied the influence of CMV infection according to the stage of HIV disease, the main effect was on progression from AIDS to death, probably because CMV disease is a late event. Sexual CMV transmission and frequent re-exposure to CMV may explain why CMV infection emerged as an important co-factor for HIV progression only in the sexual exposure group.

Acquired Immunodeficiency Syndrome↗

Do gender differences in CD4 cell counts matter?

OBJECTIVE: To examine the effect of gender on disease progression and whether gender differences in CD4 lymphocyte counts persisted for the entire course from HIV seroconversion until (death from) AIDS. METHODS: CD4 lymphocyte counts were modelled in 221 female and 443 male seroconverters following seroconversion, backwards from AIDS and backwards from death using regression analysis for repeated measurements. RESULTS: In the period before use of highly active antiretroviral therapy (HAART), progression to AIDS and to death were marginally slower in women than in men as assessed by proportional hazards analysis. Women seroconverted for HIV, developed AIDS and died at higher CD4 cell counts than men (women: 815, 146 and 44 x 10(6) cells/l, respectively; men: 727, 49 and 22 x 10(6) cells/l, respectively), although differences were only statistically significant at AIDS onset. Declines in CD4 lymphocyte counts were not significantly affected by gender and absolute differences between men and women were stable, with exception for the trajectory close to AIDS when the decline became steeper for men than women. CONCLUSION: These gender differences in CD4 lymphocyte counts suggest a delay of initiation of therapy in women compared with men (our model predicted that women reach the threshold of starting HAART at about 12 months later than men). If this delay unfavourably influences progression, treatment guidelines should be revised so that women can benefit equally from HAART.

Acquired Immunodeficiency Syndrome↗

Predictive value of viral load and other markers for progression to clinical AIDS after CD4+ cell count falls below 200/microL. SEROCO & HEMOCO Study Group.

BACKGROUND: To assess the predictive value of biological and clinical events for progression to AIDS (1993 European classification) when the CD4+ cell count falls below 200/microL (CD4 threshold) in different exposure groups. To investigate whether such markers remain predictive independently of the serum HIV-1 RNA level at the CD4 threshold. METHODS: The predictive value of biological and clinical events occurring during the 24 months prior to the occurrence of CD4 threshold (n = 333) was quantified in a Cox model. Another Cox model was carried out in a subset of 77 patients in whom viral load from stored sera was available. Furthermore, changes in viral load during the 24 months preceding the CD4 threshold were assessed in a mixed model according to subsequent development of AIDS. RESULTS: Among the 333 patients, the slope of the CD4+ cell counts, the emergence of p24 antigen, persistent thrush, and age at the CD4 threshold were independent predictors of progression to clinical AIDS (44.7%). Among the subset of 77 patients, the HIV-1 RNA level at the CD4 threshold, persistent thrush and age remained independent predictors of progression to AIDS (45.5%). The increase of the HIV-1 RNA level was moderate, both in non-progressors (24.0% per year) and in those who subsequently developed AIDS (27.1% per year), (P = 0.93). Viral load was consistently higher in the latter group (P = 0.002). CONCLUSION: At a late stage of infection, age and persistent thrush remain predictive of progression to AIDS, independently of viral load.

Acquired Immunodeficiency Syndrome↗

The use of auxiliary events to improve the analysis of survival for HIV-infected patients: application to the French Prospective Multicenter Cohort (SEROCO).

SUMMARY: A multicenter prospective cohort study, including 512 patients for whom date of HIV infection was known, showed that the use of an appropriate auxiliary event can improve the analysis of survival data and lead to an earlier detection of risk factors for HIV patients. Age at seroconversion and primary symptomatic infection were used as risk factors. Two age groups were defined as age at seroconversion >30 years (n = 203) and < or = 30 years (n = 309). Patients with primary symptomatic infection PSI (n = 215) were compared with patients without any clinical manifestation during primary infection (n = 297). Death was considered as the endpoint of primary interest and occurred in 76 patients in the study. Classical non-parametric methods (Kaplan-Meier estimate and long-rank test) and parametric regression model (Weibull model) were used for a standard analysis of survival data. A parametric approach using auxiliary information was used to estimate the survival function and to test the effect of age at seroconversion and PSI. We also applied a recently proposed distribution-free method to produce a non-parametric estimate of the survival function and to test age at seroconversion and PSI with respect to survival estimates. Both methods are compared for two distinct auxiliary events (Karnofsky score below 75 and a first drop of CD4 lymphocyte counts below 200 cells/MM3). The use of CD4 lymphocyte counts below 200 cells/MM3 as an auxiliary event improved the analysis of survival data available in December 1994. For both methods incorporating CD4 counts below 200 cells/mm3 in addition to survival data, the effect of age at seroconversion on survival was significant in April 1992 whereas it was not significant with standard methods. For PSI exposure group, results shown in this work do not indicate any improvement in using auxiliary information. Conditions for using an appropriate auxiliary event as well as advantages and shortcomings of both methods are discussed. Methods used in this work, with appropriate auxiliary information, are promising either through a reduction in the time to follow-up to detect risk factors for cohort studies or the time needed for drug development in clinical trials.

Adult↗

HEMOCO: a French prospective study of hemophiliacs infected by human immunodeficiency virus type 1 (HIV-1).

HEMOCO is a multicenter prospective cohort set up in 1989 to monitor 407 French hemophiliacs infected by HIV-1 and recruited in 4 hemophilia treatment centers in the Paris region. As of 15 July 1995, 42% of the patients in the cohort had developed stage B HIV disease and 29% stage C disease (AIDS); 23.1% of the patients had died. The cumulative proportion of patients with AIDS was 4.5% at 5 years and 27.4% at 10 years, while the respective mortality rates were 3.8% and 19.5%. In our study, only age was predictive of AIDS, with an estimated relative risk of 1.2 per 10-year age increment; this factor was also predictive of death. After 10 years of follow-up, 6.1% of the study population had no clinical or laboratory signs of immunodepression. The follow-up protocol in the HEMOCO protocol is the same as that in the French SEROCO study, which includes men infected by HIV-1 through sexual contact. This will allow us to compare the progression of HIV infection between these two exposure groups.

Acquired Immunodeficiency Syndrome↗

High risk of HIV disease progression after infection through a sexual partner with AIDS.

OBJECTIVE: To investigate whether HIV-1 infection acquired through a severely immunodepressed sexual partner increases the risk of disease progression. DESIGN: A prospective cohort of patients infected through sexual contact at a known date and enrolled a few months (median, 2 months) after their first HIV-positive test. At enrolment, 12 subjects stated having had unprotected intercourse (anal or vaginal penetration) with a partner with AIDS within the 6 months prior to their first HIV-positive test. For the same period, 60 subjects stated having had unprotected intercourse with a partner, known to be HIV-positive, but who had not developed AIDS. METHOD: The endpoint was the first occurrence of an HIV-related illness (group IV or AIDS, 1987 Centers for Disease Control and Prevention revised classification). Event-free survival curves since infection were constructed using the Kaplan-Meier method and compared by the log-rank test. The Cox model was used for multivariate analysis. RESULTS: Disease progression was more rapid among the 12 subjects who stated having sex with a person with AIDS at a time close to infection, than among the other subjects (P = 0.03). Homosexuality and age at infection were also related to HIV disease progression. The adjusted relative risk of developing an HIV-related illness among those 12 subjects was 3.9 (95% confidence interval, 1.5-9.9). CONCLUSION: Our results confirm the influence of virus-related factors on the onset of immunodepression in subjects infected through sexual contact.

Acquired Immunodeficiency Syndrome↗

Influence of neurologic manifestations of primary human immunodeficiency virus infection on disease progression. SEROCO Study Group.

To determine the influence of neurologic manifestations of primary human immunodeficiency virus (HIV) infection on disease progression, 277 nonhemophiliac adults enrolled < 1 year after HIV infection were studied. Patients with neurologic manifestations during symptomatic primary HIV infection (PSI) (group N+; n = 23), with nonneurologic manifestations (group N-; n = 112) during PSI, and without any clinical manifestation during primary infection (group NPI; n = 142) were compared for disease progression. Age at infection, sex, mode of infection and CD4+ cell count at first visit did not differ between groups. In a Cox model, the relative risk (RR) of developing AIDS was 6.11 (95% confidence interval [CI], 1.94-19.28) in group N+ and 2.32 (95% CI, 0.93-5.83) in group N- compared with group NPI. The RR of AIDS onset after adjustment for treatment and age at infection was, respectively, 4.65 (95% CI, 1.43-15.03) and 2.03 (95% CI, 0.80-5.19) in groups N+ and N-. Neurologic manifestations of primary HIV infection are associated with an accelerated progression of disease.

Adult↗

[Multicenter French cohort of adults with HIV infection. Description and course after 4 years of follow-up. SEROCO].

OBJECTIVES: A prospective multicentric epidemiological study (SEROCO) of subjects with a diagnosis of human immunodeficiency virus (HIV) infection was started on January 1, 1988 in order to better understand the natural history of HIV infection and factors related to outcome. Observations after 4 years of follow-up are reported here. METHODS: After authorization by the French national ethics committee and the national commission for personal freedom, 18 French centres included non-haemophiliac volunteers who were asymptomatic, had had non anti-HIV treatment and whose HIV positivity had been known less than 1 year at inclusion. These last three criteria were not required for patients whose precise date of contamination was known within a range of +/- 3 months. RESULTS: On July 15, 1992, there were 1453 infected subjects in the cohort (1063 males, 417 females; age range at inclusion 18-75 years; mean age 31.3 +/- 9.4). Globally, 2.7% of the subjects were symptomatic at inclusion. Mean CD4 lymphocyte count at inclusion was 508/mm3. Clinically, 51.5% of the patients had a history of sexually transmitted disease at inclusion. After 4 years (on July 15, 1992) mean follow-up was 28 +/- 12.9 months for a total of 3428 patient-years. Disease progression to stage IV was observed in 439 patients including 202 who developed the acquired immuno-deficiency syndrome (AIDS). Among these 202 patients, 113 had died at the end-point of this report. The first manifestation of AIDS was Kaposi sarcoma in 44, pulmonary pneumocystosis in 38 and cerebral toxoplasmosis in 27. The probability of developing AIDS was calculated at 13.9% at 5 years, 27.7% at 7 years and 33.7% at 10 years. The probability of a CD4 count below 200/mm3 was 32.7, 55.6 and 67% at 5, 7 and 10 years respectively. For patients with a CD4 count below 200, the probability of developing AIDS was 18% at 1 year, 39% at 2 years and 51% at 3 years. CONCLUSIONS: SEROCO has been a most useful prospective epidemiological tool due to the diversity of the subjects included. The observed natural history of HIV infection will lead to specific research projects aimed at better understanding the disease process.

Acquired Immunodeficiency Syndrome↗

Effect of age and exposure group on the onset of AIDS in heterosexual and homosexual HIV-infected patients. SEROCO Study Group.

OBJECTIVE: To analyse the influence of age at seroconversion and sexual exposure group on the progression of HIV disease. DESIGN: This multicentre prospective cohort study involved 443 subjects whose date of HIV infection was known to within +/- 1 year. Individuals whose sexual behaviour was exclusively heterosexual after HIV infection constituted the heterosexual group (n = 131). AIDS-free survival was compared with that of men (n = 312) infected through homosexual sex and who continued homosexual activity after HIV infection. They constituted the homosexual group. METHODS: The end-point was the onset of an AIDS-defining illness listed in the 1987 revised Centers for Disease Control and Prevention (CDC) criteria. Using the Kaplan-Meier method, AIDS-free survival curves were plotted for three age categories (< 20, 20-39, > or = 40 years). A Cox model was used to quantify the effect of age and to assess the influence of exposure group on AIDS onset after adjustment for age. Because of the high incidence of Kaposi's sarcoma (KS) among homosexual men, a disease that can be an early AIDS-defining illness, multivariate analysis was performed with and without consideration of the occurrence of KS. RESULTS: Patients aged > or = 40 years at seroconversion progressed more rapidly to AIDS than younger patients (P < 0.006). When age was fitted as a continuous variable and adjusted for exposure group, the relative risk of developing AIDS by any time after seroconversion was 1.34 for a 10-year increase difference [P = 0.03; 95% confidence interval (CI), 1.03-1.77]. After adjustment for age, the relative risk of developing AIDS (CDC criteria) was 2.42 (P = 0.008; 95% CI, 1.18-4.97) among the homosexual men (AIDS cases, n = 56). All cases of KS (n = 19) involved the homosexual group. Excluding KS as a first manifestation of AIDS, homosexual or bisexual subjects had a risk of AIDS of 1.92 (P = 0.07; 95% CI, 0.92-4.03) compared with heterosexual subjects. CONCLUSIONS: The risk of AIDS increases with age at seroconversion. The more rapid progression towards AIDS in the homosexual group than in the heterosexual group persisted after adjustment for age. Further studies are required to determine the possible role of repeated exposure to HIV or other pathogens acquired sexually.

Acquired Immunodeficiency Syndrome↗