BACKGROUND:Highly active antiretroviral therapy (HAART) has dramatically improved the prognosis for patients with HIV. There is ongoing debate over a potential gender effect on patient outcome after ...HAART.
METHODS:Individuals were from the EuroSIDA cohort, naive to protease inhibitors and nonnucleoside reverse transcriptase inhibitors, and had at least one viral load and CD4 measurement prior to starting HAART. Endpoints were virologic (time to <500 copies/mL, time to rebound first of two consecutive viral loads >500 copies/mL), immunologic (time to a 100/mm cell rise in CD4 count) and clinical (time to new AIDS and death).Hazard ratios (HR), derived using Cox regression models, compared female to male rates of achieving endpoints.
RESULTS:Of 2547 patients, 20% (511) were female. Significantly more females than males were nonwhite (24% vs. 10%, p < .001). Males were older (median age 39 vs. 35 years, p < .0001), had lower CD4 counts (211 vs. 240/mm, p = .03), higher viral loads (4.6 vs. 4.4 log copies/mL, p < .0001), were more likely to have a history of AIDS (26% vs. 18%, p < .001) and were more likely to be treatment-naive (34% vs. 29%, p = .03). Adjusted HR for association between gender (comparing females with males) and the outcomes studied were as followsfor reaching <500 copies/mL 0.91 (0.81-1.03, p = .17), rebound 1.17 (0.95-1.44, p = .15), for 100 cell CD4 count rise 1.02 (0.88-1.14, p = .99), for progression to new AIDS 1.12 (0.73-1.71, p = .59) and for time to death 1.15 (0.69-1.92, p = .57).
CONCLUSIONS:We found no significant evidence of a gender difference in virologic, immunologic, or clinical outcomes after starting HAART.
1 Department of Virology, Swedish Institute for Infectious Disease Control and Microbiology and Tumorbiology Center, Karolinska Institutet, SE-171 82 Solna, Sweden
2 Unit of Virology, Division of ...Medical Microbiology, Department of Laboratory Medicine, Lund University, SE-223 62 Lund, Sweden
3 Department of Infectious Diseases/Solna, Karolinska University Hospital, Karolinska Institutet, SE-171 76 Stockholm, Sweden
4 Department of Infectious Diseases/Huddinge, Karolinska University Hospital, Karolinska Institutet, SE-141 86 Stockholm, Sweden
Correspondence Jan Albert Jan.Albert{at}smi.ki.se
To investigate why human immunodeficiency virus type 2 (HIV-2) is less virulent than HIV-1, the evolution of coreceptor usage, autologous neutralization, envelope sequence and glycosylation was studied in sequentially obtained virus isolates and sera from four HIV-2-infected individuals. Neutralization of primary HIV-2 isolates was tested by a cell line-based assay and IgG purified from patients' sera. Significant autologous neutralization was observed for the majority (39 of 54) of the HIV-2 serumvirus combinations tested, indicating that neutralization escape is rare in HIV-2 infection. Furthermore, sera from 18 HIV-2 patients displayed extensive heterologous cross-neutralization when tested against a panel of six primary HIV-2 isolates. This indicates that HIV-2 is intrinsically more sensitive to antibody neutralization than HIV-1. In line with earlier reports, HIV-2 isolates could use several alternative receptors in addition to the major coreceptors CCR5 and CXCR4. Intrapatient evolution from CCR5 use to CXCR4 use was documented for the first time. Furthermore, CXCR4 use was linked to the immunological status of the patients. Thus, all CXCR4-using isolates, except one, were obtained from patients with CD4 counts below 200 cells µl 1 . Sequence analysis revealed an association between coreceptor usage and charge of the V3 loop of the HIV-2 envelope, as well as an association between the rate of disease progression and the glycosylation pattern of the envelope protein. Furthermore, HIV-2 isolates had fewer glycosylation sites in the V3 domain than HIV-1 (two to three versus four to five). It is proposed here that HIV-2 has a more open and accessible V3 domain than HIV-1, due to differences in glycan packing, and that this may explain its broader coreceptor usage and greater sensitivity to neutralizing antibodies.
An amino acid sequence alignment of the V1, V2 and V3 domains of the HIV-2 envelope protein is available as supplementary material in JGV Online.
The GenBank/EMBL/DDBJ accession numbers for the sequences determined in this study are DQ213026DQ213040.
This study investigated the incidence of pancreatitis and its association with antiretroviral therapy (ART), focussing on stavudine and didanosine.
EuroSIDA has collected information on pancreatitis ...since Summer 2001. All identified cases have been verified by the coordinating centre. Individuals were followed from June 2001 or the date of entry into EuroSIDA (whichever occurred later) until a diagnosis of pancreatitis or the last study visit. Factors associated with pancreatitis were investigated using Poisson regression. Cumulative lengths of exposure to didanosine without stavudine, stavudine without didanosine, stavudine with didanosine, and other ART were time-updated variables. Treatment variables were fitted with a 6-month time lag.
There were 43 (nine presumptive) pancreatic events in 9678 individuals during 33 742 person-years (incidence 1.27/1000 person-years). The incidence among those with no, 2 or less and over 2 years' exposure to ART including stavudine and didanosine was 1.24, 1.73 and 0.78/1000 person-years, respectively. In multivariable analysis, higher baseline CD4 cell counts were associated with a decreased risk of pancreatitis. There was no evidence of an association of pancreatitis with cumulative exposure to didanosine and stavudine, didanosine without stavudine, stavudine without didanosine, or other ART.
We observed a low overall rate of pancreatitis in the years 2001-2006, and did not find an association of an increased incidence of pancreatitis with cumulative exposure to antiretroviral agents generally, and to didanosine and stavudine in particular.
To perform a European sentinel surveillance study for antimicrobial resistance (AMR) in Neisseria gonorrhoeae as part of the European Surveillance of Sexually Transmitted Infections Programme.
From ...2006 to 2008 17 countries participated in the AMR surveillance programme. The susceptibility of a total of 3528 consecutive isolates was tested using the agar dilution breakpoint technique or Etests for ciprofloxacin, penicillin, tetracycline, azithromycin, spectinomycin and ceftriaxone. Nitrocefin was used to detect β-lactamase activity.
Rates of resistance to ciprofloxacin, the previously recommended treatment, were high across Europe (42-52%), indicating that usage is no longer appropriate. Although resistance to the currently recommended treatment, ceftriaxone, was not demonstrated, a concerning upward drift in the minimal inhibitory concentration (MIC) distribution was identified since an earlier European study in 2004. No resistance to spectinomycin was seen, whereas azithromycin resistance varied from 2% to 7% and isolates from Scotland (n=4) and Ireland (n=1) showed high-level resistance (MIC >256 mg/l). High-level resistance to tetracycline and penicillin remained relatively constant at 16% and 12%, respectively.
AMR is an ongoing problem in Europe, with high rates of resistance to many previously recommended therapeutic agents observed in many European countries. Continual European and global surveillance of AMR in N gonorrhoeae is essential to monitor for increasing, emerging and high-level resistance to therapeutically relevant agents and to inform treatment guidelines so optimum treatments are administered.
Objective: To determine the sensitivity of 33 currently available and seven earlier tests for the detection of HIV or HIV antibody in primary HIV-1 infection, to estimate the duration of the 'window ...period' and the influence of early initiated antiretroviral treatment (ART). Design: A prospective cohort study of 38 patients with primary HIV-1 infection. ART was initiated at a median time of 13 (range 0-23) days after the onset of symptoms in 10 patients. Main outcome measures: The time from infection to onset of symptoms and from onset of symptoms to the appearance of HIV antibody as measured by 36 different tests, and the start and duration of viraemia, as detected by four different tests. Results: The illness appeared 13-15 days after infection in 12 of 15 determinable cases, and seroconversion was detected within 1-2 weeks after the onset of illness by 27 of 30 currently available tests for HIV antibody, in contrast to the 2-7 weeks or more needed by the old tests. HIV RNA appeared during the week preceding the onset of illness and was detected in all subsequent samples, except when ART had been initiated, which also induced a delay of the antibody response. Conclusion: Many tests for HIV or HIV antibody can now be employed for an early confirmation of primary HIV infection (PHI). Currently available screening tests proved much more sensitive than older tests, and seroconversion was usually detected within one month after infection. Consequently, in Sweden we now recommend only 3 months of follow-up after most cases of HIV exposure.
Objectives
Deficits in cognitive function remain prevalent in HIV‐infected individuals. The aim of this European multicentre study was to assess factors associated with cognitive function in ...antiretroviral therapy (ART)‐naïve HIV‐infected subjects at the time of enrolment in the NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 study.
Methods
Prior to starting ART, seven cognitive tests exploring domains including episodic memory, verbal fluency, executive function and psychomotor speed were administered with scores standardized to z‐score using the study population sample mean and standard deviation. The primary measure was overall z‐score average (NPZ). We assessed associations between baseline factors and test results using multivariable regression models.
Results
Of 283 subjects with baseline cognitive assessments, 90% were male and 12% of black ethnicity. Median (interquartile range) age, years of education, years of known HIV infection, baseline CD4 count and baseline HIV RNA were 39 (31, 47) years, 13 (11, 17) years, 1 (0, 4) years, 344 (279, 410) cells/μL and 4.74 (4.28, 5.14) log10 HIV‐1 RNA copies/mL, respectively. Forty per cent were current smokers. Factors significantly associated with poorer overall cognitive performance in multivariable models included older age, shorter duration of education, black ethnicity, lower height, and lower plasma HIV RNA.
Conclusions
In this large, European‐wide, ART‐naïve population with relatively preserved immunity and early HIV infection, cognitive function scores at the time of ART initiation were associated with demographic and HIV‐disease factors.
Objectives: To study the natural course of viremia during primary HIV infection (PHI). Method: Eight patients were followed from a median of 5 days from the onset of PHI illness. Plasma HIV-1 RNA ...levels were measured frequently and the results were fitted to mathematical models. HIV-1 RNA levels were also monitored in nine patients given two reverse transcriptase inhibitors and a protease inhibitor after a median of 7 days from the onset of PHI illness. Results: HIV-1 RNA appeared in the blood during the week preceding onset of PHI illness and increased rapidly during the first viremic phase, reaching a peak at a mean of 7 days after onset of illness. This was followed by a phase of rapidly decreasing levels of HIV-1 RNA to an average of 21 days after onset. Viral density continued to decline thereafter but at a 5- to 50-fold lower rate; a steady-state level was reached at a median of 2 months after onset of PHI. Peak viral density levels correlated significantly with levels measured between days 50 and 600. Initiation of antiretroviral treatment during PHI resulted in rapidly declining levels to below 50 copies/ml. Conclusions: This study demonstrates the kinetic phases of viremia during PHI and indicates two new contributions to the natural history of HIV-1 infection: PHI peak levels correlate with steady-state levels and HIV-1 RNA declines biphasically; an initial rapid decay is usually followed by a slow decay, which is similar to the initial changes seen with antiviral treatment.
The spread of hepatitis C virus (HCV) in Sweden in the 1970s indicated that serious liver complications (SLC) would increase in the 2000s. The aim of this study was to analyse the burden of ...HCV‐associated inpatient care in Sweden, to demonstrate the changes over time and to compare the findings with a noninfected population. The HCV‐cohort (n: 43 000) was identified from the national surveillance database 1990–2006, and then linked to national registers to produce an age‐, sex‐, and region‐matched noninfected comparison population (n: 215 000) and to obtain information on demographics, cancers, inpatient care and prescriptions. Cox regression was used to estimate the likelihood (hazard ratios) for admission to hospital in the HCV compared with the noninfected cohort. The hazard ratios were 4.03 (95% CI: 3.98–4.08) for all care, 77.52 (71.02–84.60) for liver‐related care and 40.74 (30.58–54.27) for liver cancer care. The admission rate in the HCV‐cohort compared with the noninfected cohort, the rate ratio (age‐ and sex‐adjusted) for all inpatient care was 5.91 (95% CI: 5.87–5.94), and the rate ratio for liver‐related care was 70.05 (66.06–74.28). In the HCV‐cohort, 45% of all episodes were for psychiatric, mostly drug‐related, care. Inpatient care for SLC increased in the 2000s. To conclude, drug‐related care was common in the HCV‐infected cohort, the demand for liver‐related care was very high, and SLC increased notably in the 2000s, indicating that the burden of inpatient care from serious liver disease in HCV‐infected individuals in Sweden is an increasing problem.
Abstract
Objective. The aim of this nationwide cohort study was to assess the risk for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection or HBV and hepatitis C ...virus (HCV) co-infection in Sweden, a low endemic country. Material and methods. A total of 12,080 patients with HBV and 3238 patients with HBV-HCV co-infection were notified to the Swedish institute for Infectious Disease Control between 1990 and 2004. After excluding 1850 patients with acute HBV and 584 patients infected in adult life, we analyzed the cohort of 9646 subjects with chronic HBV infection. In the co-infection cohort, 1697 patients were analyzed after excluding 1541 cases with acute HBV. The Swedish national cancer registry was used for follow-up. The HCC incidence rate in the cohorts was compared with the HCC incidence rate in the general population and the standardized incidence ratio (SIR) was calculated for different strata according to estimated infection period. Results. HCC was found in 45 patients in the HBV cohort. In the stratum of 40-49 years of infection we found a SIR of 47 and in stratum 50-59 years the SIR was 54. In the co-infected cohort 10 HCCs were found. The SIR in the stratum 20-29 years of infection was 34 and the SIR in the stratum 30 years and over was 91. Conclusions. This national cohort study of HBV infected and HBV-HCV co-infected subjects in a low endemic country confirms a highly increased risk of liver cancer compared to the general population.
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