Objectives:To analyse the incidence, prevalence, and predictors for development of triple-class antiretroviral drug failure (TCF) in individuals infected with HIV. Design:Population-based observational cohort study from 1 January 1995 to 31 December 2003, focusing on all 2722 recipients of highly active antiretroviral therapy (HAART) in Denmark. Methods:We used person-years analysis, Kaplan–Meier survival curves and Cox regression analysis. TCF was defined as a minimum of 120 days with viral load > 1000 copies/ml on treatment with each of the three major drug classes. Results:We observed 177 TCFs, yielding a crude incidence rate (IR) of 1.8 per 100 person-years [95% confidence interval (CI), 1.6–2.1]. Seven years after initiation of HAART, 17.2% (95% CI, 14.5–20.5) of antiretroviral (ART)-experienced patients, but only 7.0% (95% CI, 4.3–11.2) of ART-naive patients were estimated to have failed. After an initial rise, the IR from the third to the sixth year of HAART declined significantly for ART-experienced patients [incidence rate ratio (IRR), 0.80 per year (95% CI, 0.66–0.97); P = 0.022], and non-significantly for ART-naive patients [IRR, 0.79 per year (95% CI, 0.53–1.18); P = 0.255]. The IR for all patients being followed each year declined from 1997 to 2003 [IRR, 0.88 (95% CI, 0.81–0.96); P = 0.002]. The prevalence of TCF remained stable at less than 7% after 2000. Predictors of TCF at commencement of HAART were a CD4 cell count below 200, a previous AIDS-defining event, previous antiretroviral exposure, earlier year of HAART initiation, and young age. Conclusions:The risk of TCF is declining in Denmark and the prevalence remains stable.

The objective of this study was to investigate the presence of non-subtype B HIV-1 in Denmark. The C2-V3-C3 region of the env gene from proviral DNA obtained from patients suspected of being infected with non-subtype B virus was PCR-amplified and directly sequenced. The DNA sequences were aligned with full-length HIV-1 reference strains from each subtype and analysed using the phylogenetic package PHYLIP 3.1. The neighbour-joining method was used with 100 bootstraps. Of the 144 patients included in this study C2-V3-C3 sequences were obtained from 129 patients (90%). The phylogenetic analyses showed that virus from 49 patients (38%) was subtype A, 39 (30%) subtype C, 9 (7%) subtype D, 14 (11%) subtype CRF01_AE, 16 (12%) subtype B, 1 (1%) subtype F and 1 (1%) subtype J. This study demonstrates that almost all subtypes can be detected in Denmark; all non-subtype B infections could be traced to countries with a high prevalence of non-subtype B virus.

Background: commercial HIV-1 qualitative DNA PCR tests have the potential to detect virus in patients in whom antibody tests may be ineffective, such as patients with primary HIV infection and infants born to HIV seropositive mothers. However, the genetic diversity of HIV-1 raises concern about the ability of the PCR tests to detect all current subtypes. Objectives: to asses the sensitivity of the Amplicor HIV-1 test on 126 whole-blood samples representing seven different subtypes and to investigate the sensitivity when the standard assay was modified by including the primer pair SK145 and SKCC1B. Results: of the 126 HIV-1 infected persons, 113 were tested positive and 13 were DNA PCR negative. On the basis of these results, the standard Amplicor HIV-1 test had a sensitivity of 90% in our cohort. In addition, 9% of the positive samples showed a low reactivity but above the cut-off of the assay. The standard assay yielded sensitivities of 100% for subtype B (n=16), D (n=9) and G (n=1), but only 83% for subtype A (n=41), 98% for subtype C (n=43), 79% for subtype E (n=14) and 0% for subtype F (n=2). All samples with low reactivity were non-B subtype. Eight of the DNA PCR negative samples, four subtype A, one C and three E were amplified with the modified Amplicor HIV-1 test with addition of SK145/SKCC1B primers. Using this modified protocol, six samples out of eight became positive. However, two samples (one A and one C) remained DNA PCR negative. Conclusion: this study confirms that the Amplicor HIV-1 test does not detect all subtypes with equivalent sensitivity and 10% of the samples, tested negative. Thus, it is preferable to add the SK145/SKCC1B primers to the standard test, where infection with non-B subtype is suspected.

Pneumococcal infections are frequently observed in patients with human immunodeficiency virus (HIV) infection and active immunization has been recommended as prophylaxis in this patient group. We studied 103 out-patients with asymptomatic or mildly symptomatic HIV infection with respect to specific IgG and IgG2 pneumococcal antibodies before and after vaccination with a 23-valent pneumococcal polysaccharide vaccine. A significant increase ( > 2-fold) in IgG and IgG2 antibody levels was observed after 1 month in 69/103 patients (67%) with no correlation with the CD4 cell count at the time of vaccination. The response rate was not influenced by concurrent treatment with anti-retroviral monotherapy, or by age or gender. After immunization a strong correlation between IgG and IgG2 anti-pneumococcal antibodies was demonstrated. Nevertheless, 12 months after vaccination the specific antibody titres were not significantly different from pre-vaccination values. In conclusion, antibodies induced by pneumococcal vaccination in patients with HIV infection have a short duration. This raises the question as to whether vaccination will have any impact on clinical end-point in this group of patients.

In 1990-91, 237 female sex workers from Copenhagen were enrolled in a larger study performed in 9 European countries. None of 206 women accepting serological testing was HIV-infected despite the fact that 36 (17.5%) were injecting drug users (IDU). Whereas 95% of the women always used condoms with clients over the last 6 months, this proportion was 25% and 9% respectively for casual and regular non-paying partners (P < 0.0001 for both comparisons). Those reporting at least one STD over the last year had more non-paying sexual partners than the others (P < 0.01) and the frequency of STD was lower in women who always used condoms with non-paying partners (7% vs 31%, P = 0.01). Women working on the street were more often IDU than others (78% vs 7%, P < 0.001). Independently of drug use, street prostitutes also tended to have more clients (P = 0.007) and more STD (P = 0.05). The striking differences in condom use with clients as compared to non-paying partners and the association between STD and sexual behaviours with such partners but not with clients show that specific interventions should be designed to promote safer sex with non-paying partners.

In a community study, the HIV-1 and HIV-2 antibody status of the inhabitants of 100 randomly chosen houses in Bissau, West Africa, were followed from 1987 to 1989. There was no HIV-1 infection alone, while the HIV-2 seroprevalence in adults was 8.9% (58 of 652) in 1987 and 10.1% (61 of 603) in 1989. HIV-2 seroprevalence in 15- to 39-year-olds was 6.1% in 1987 and 11.3% in newcomers in 1989 [the Mantel-Haentzel weighted relative risk (RRMH) = 1.86; 95% confidence interval (CI): 1.07-3.24]. Three hundred thirty adults who were HIV-2 seronegative in 1987 were reexamined in 1989; seven had seroconverted. Follow-up time was 700 person years, giving an incidence of HIV-2 infection of 1 per 100 person years. With a history of sexually transmitted disease (STD), the RR of seroconverting was 9.95 (2.31-42.80). Blood transfusions received since 1987 did not result in seroconversions. No case of vertical transmission of HIV-2 was seen. There was an excess mortality in those who were HIV-2 seropositive; however, it was statistically significant only for children (RR = 22.27; 95% CI: 6.92-71.70; p < 0.0001), not for adults (RR = 2.16; 95% CI: 0.81-5.76; p = 0.23), when considering death from disease only.

In order to evaluate the role of sexual transmission and parenteral transmission of hepatitis C virus (HCV) in homosexual men and intravenous drug users (IVDU) serum samples from 147 homosexual men and 126 IVDU were tested for anti-HCV. Anti-HCV was found in two (1.4%) of the homosexual men and in 123 (98%) of IVDU. The presence of anti-HCV could not be correlated to the presence of HBV markers or HIV-antibodies. HCV is widespread among Danish IVDU. Risk of sexual transmission seems low even though sexual contact is a much more prevalent risk factor than needle sharing.

A collection of 3019 selected serum samples (ss), comprising 329 ss from intravenous drug abusers, 558 ss from homosexual men, 682 samples from persons attending a STD clinic, 100 ss from individuals of African origin, 300 ss from sexual contacts to Africans, 650 ss from Danish blood donors who resided in Africa greater than 2 years prior to donating the ss, and 400 ss with equivocal antibody reactions in an HIV-1 Western blot was tested for antibodies against HIV-2 by in-house HIV-2 ELISA and Western blot. Four ss were positive for antibodies against HIV-2. Three of the ss originated from West African men, the fourth belonged to the spouse of one of these men. Three of the samples presented with an uncharacteristic reaction in a HIV-1 Western blot. The study indicates that HIV-2 infection is not yet widespread in Denmark and that it remains closely related to West Africa.

Twenty-nine human immunodeficiency virus type 2 (HIV-2) seropositive women identified in a cross-sectional study in Bissau in 1987 participated in a follow-up study in 1988, where each was matched for age and marital status with two HIV-2 seronegative women. Detailed information about all pregnancies was obtained. The HIV-2 seropositive women and their controls had similar mean numbers of pregnancies, live children, children who died, and abortions. The HIV-2 seropositive women did not have a greater risk of having had an abortion or a child who died than did the HIV-2 seronegative women. No difference in survival was seen between children born to HIV-2 seropositive and HIV-2 seronegative women. The H/S-ratios and CD4 numbers were lower in the seropositive group, but none had values lower than 0.4 and 0.4 x 10(9)/L, respectively. Seven prospectively observed children born to HIV-2 seropositive mothers showed no sign of infection. The lack of evidence of transmission of HIV-2 from mother to child is suggested to be due to the absence of marked immunodeficiency in this random sample of the general population.

A novel competition ELISA for detection of antibodies against HIV-1 was developed. The assay is based on competition at the single epitope level and utilises a human monoclonal antibody and an E. coli-produced fragment of the transmembrane glycoprotein gp41. The sensitivity of the assay was 100% in tests on 247 serum samples obtained from 219 individuals previously shown to be HIV-1 antibody positive by both conventional indirect ELISA and the immunoblotting test. The patients represented various clinical and immunological stages of HIV-1 infection. Likewise, the specificity of the assay was 100% in tests on 105 serum samples from normal individuals previously tested negative by indirect ELISA. Further, among 105 serum samples selected due to consistent false positive reactions in the indirect ELISA only 2 samples (1.9%) demonstrated false positive reactions in the competition ELISA, i.e. 98.1% specificity. Finally, only 2 of 57 (3.5%) serum samples from HIV-2 infected individuals showed positive reactions in the assay, while 54 (94.7%) had absorbance values similar to the negative controls. These results demonstrate that human monoclonal antibodies may form the basis for highly sensitive and specific assays for detection of antibodies to HIV-1.

During four study periods, each of 3-4 weeks' duration in 1987 and 1988, all patients attending the Copenhagen outpatient Venereal Disease Clinic were encouraged to have a test for human immunodeficiency virus (HIV) antibody. Anonymous testing or testing for research purposes only without any data was also offered. Patients known to be HIV antibody-positive were not re-tested. A total of 1753 patients (1118 men, 635 women) were counselled and testing recommended. Testing was refused by 255 patients, 57 of whom had been tested (all negative) within the previous 3 months. HIV serology was therefore unknown in 11.7% (198 of 1696 persons), including 120 of 922 heterosexual men (13%), 16 of 159 homo/bisexual men (10%) and 62 of 615 women (10%). There was no substantial difference between the four study periods in the numbers refusing the test. Sixteen of the 1498 patients tested were HIV antibody-positive, including one woman and 3 men with a history of intravenous drug abuse and 11 homo/bisexual men; one heterosexual man with HIV antibodies had no known risk behaviour. It is concluded that HIV testing with informed consent at a sexually transmitted disease clinic will not include all persons, and therefore will not exclude a self-selection bias. Surveillance studies using unlinked HIV testing are therefore necessary and it is recommended that they should be performed in Denmark. In this study, unlinked HIV testing of the serum specimens taken for syphilis serology would have decreased the percentage of 'non-attenders' from 12.4% to 0.8% during the final study period.

In order to describe the risk pattern including sexual behaviour among HIV-infected women in Copenhagen we studied the charts of all women tested seropositive between January 1985 and August 1988 in the three main hospitals handling HIV/AIDS. One hundred and fifteen women were positive for HIV antibodies: 35 (31%) were infected by heterosexual contact and 63 (55%) were intravenous drug users. Among the heterosexually transmitted cases 25 (71%) had intercourse with a man from a high risk group and nine women had intercourse with a known HIV antibody positive man without known risk factors. Use of condoms was claimed by 31% of the heterosexually-transmitted women before the HIV test, and by 74% (P = 0.002) after the test. In 1988 73% of the women tested HIV positive were infected by heterosexual contact, in 1985 only 14%. We conclude that among HIV infected women in Copenhagen heterosexual transmission is a problem. These women seem to change sexual behaviour when informed about HIV positivity.

In a community study in Guinea-Bissau, West Africa, 47 HIV-2-seropositive cases and 87 matched controls were evaluated immunologically using immuno-alkaline phosphatase linked to avidin-biotin complex for the assessment of CD4 and CD8 status. HIV-2-seropositive individuals had significantly lower total numbers of CD4 cells and CD4/CD8 ratios, 38% having a total number of CD4 cells less-than-or-equal-to 0.5 x 10(9)/l and 36% having a CD4/CD8 ratio less-than-or-equal-to 0.8. Total numbers of CD4 cell less-than-or-equal-to 0.5 x 10(9)/l or CD4/CD8 ratio less-than-or-equal-to 0.8 were found in 53% of the HIV-2 seropositives compared with 11% among controls [odds ratio (OR) = 7.3; 95% confidence interval (CI): 3.1-17.1]. Lymphadenopathy was significantly more frequent among HIV-2 seropositives than among controls (OR = 3.4; 95% CI: 1.5-7.6). HIV-2 seropositives with lymphadenopathy had significantly fewer lymphocytes (P = 0.008) and lower total CD4 (P = 0.029) and total CD8 number (P = 0.011) than HIV-2 seropositives without lymphadenopathy. This study indicates that HIV-2 has a significant immunosuppressive effect.

In early 1988 physicians from the Muhimbili Medical Centre in Morogoro Tanzania collected sera from 106 individuals to evaluate the application of the Western blot test as a confirmatory test for HIV-1 and HIV-2 in Africa. the physicians divided the samples between a low risk group (dental patients pregnant women and health clinics staff) and a high risk group (inpatients). Laboratory personnel tested all samples for HIV-1 and HIV-2 using a commercial ELISA test. Further no matter what the result of the ELISA test they tested all samples using HIV-1 and HIV-2 Western Blot tests. 15 samples continuously tested positive on 2 of the 4 anti-HIV-1 ELISA kits. Further 11 samples tested positive by HIV-1 Western Blot test for an overall prevalence of 10%. The researchers considered this a high prevalence. Moreover a high prevalence (31%) of the sera could not be determined as positive or negative using the HIV-1 Western Blot test. In this group 82% contained gag-related bands only. 58% were negative using the HIV-1 Western Blot test. 23 samples repeatedly tested reactive using the HIV- 2 ELISA test especially those in the HIV-1 Western Blot positive group. Since no HIV-2 incidence was found HIV-2 cannot explain the indeterminate HIV-1 Western Blot results. Additional research to interpret the nature and significance of these indeterminate results is warranted. The researchers suggest that longitudinal studies be conducted to determine if indeterminate results indicate a true HIV infection.

Vox SanguinisVolume 56, Issue 2 p. 131-132 HIV-Antibody Testing and False-Positive p24 Reactivity Birgit Kvinesdal MD, Corresponding Author Birgit Kvinesdal MD AIDS Laboratory/Rubella Department, Statens Seruminstitut, Copenhagen, DenmarkAIDS Laboratory/Rubella Department Statens Seruminstitut Amager Boulevard 80 DK–2300 Copenhagen S (Denmark)Search for more papers by this authorEdgar Lauritzen, Edgar Lauritzen AIDS Laboratory/Rubella Department, Statens Seruminstitut, Copenhagen, DenmarkSearch for more papers by this authorAnne-Grethe Poulsen, Anne-Grethe Poulsen AIDS Laboratory/Rubella Department, Statens Seruminstitut, Copenhagen, DenmarkSearch for more papers by this authorBent Faber Vestergaard, Bent Faber Vestergaard Enterovirus Department, Statens Seruminstitut, Copenhagen, DenmarkSearch for more papers by this author Birgit Kvinesdal MD, Corresponding Author Birgit Kvinesdal MD AIDS Laboratory/Rubella Department, Statens Seruminstitut, Copenhagen, DenmarkAIDS Laboratory/Rubella Department Statens Seruminstitut Amager Boulevard 80 DK–2300 Copenhagen S (Denmark)Search for more papers by this authorEdgar Lauritzen, Edgar Lauritzen AIDS Laboratory/Rubella Department, Statens Seruminstitut, Copenhagen, DenmarkSearch for more papers by this authorAnne-Grethe Poulsen, Anne-Grethe Poulsen AIDS Laboratory/Rubella Department, Statens Seruminstitut, Copenhagen, DenmarkSearch for more papers by this authorBent Faber Vestergaard, Bent Faber Vestergaard Enterovirus Department, Statens Seruminstitut, Copenhagen, DenmarkSearch for more papers by this author First published: March 1989 https://doi.org/10.1111/j.1423-0410.1989.tb04965.xCitations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume56, Issue2March 1989Pages 131-132 RelatedInformation

In a community based prevalence study of HIV infection in Bissau, West Africa, 1987, the population in 100 randomly selected "houses" was asked to participate. 89% (1329/1499) were examined and had a blood sample taken. None was HIV-1 seropositive but 4.7% were seropositive for HIV-2 (0.6% in children, 8.9% in those aged 15 years and over, and 20% in those aged 40 years and over). There was no significant difference in seroprevalence between areas or ethnic groups or between individuals of different civil status when age was taken into account. Sexual contact and blood transfusions were the dominant transmission routes, and no case of vertical transmission was identified. The HIV-2 seroprevalence in spouses of HIV-2 seropositive index persons was 40%. For a history of blood transfusion the relative risk of being HIV-2 seropositive was 103.6 in children and 2.4 for adults. After exclusion of spouses, no clustering of HIV-2 seropositivity was seen. At follow-up, after a mean observation time of 325 days, there was an excess mortality for HIV-2 seropositives. The relative risk of dying for HIV-2 seropositive children was 60.8 and for adults 5.0.

The population in 100 randomly selected «houses» was asked to participate. 89% (1329/1499) were examined and had a blood sample taken