Madeleine von Sydow

Diagnosis of primary HIV-1 infection and duration of follow-up after HIV exposure

ObjectiveTo 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). DesignA 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 measuresThe 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. ResultsThe 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. ConclusionMany 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.

Immunological changes in primary HIV-1 infection

Homosexual men with symptomatic primary HIV-1 infection displayed a pronounced lymphopaenia with significantly depressed numbers of CD3+, CD4+ and CD8+ cells and B cells during the first week of illness. Subsequently, the CD8+ cell counts rose in parallel with numbers of CD3+ cells, atypical lymphocytes and activated (CD38+ and HLA-Dr+) cells to attain maximal levels about a month following onset of illness. In contrast CD4+ and B cell numbers remained low for an extended period of time. Early signs of a host response included a transient appearance of interferon-alpha in the blood and raised levels of neopterin and beta 2-microglobulin (beta 2-M). Neither CD4+/CD8+ cell ratio nor beta 2-M resumed completely normal values during a follow-up period of 2 years. These findings shed some light on pathogenetic events during early HIV-1 infection and suggest that the infection, following the acute symptomatic stage, usually enters a stage of chronic active rather than latent infection.

Zidovudine in the management of primary Hiv-1 infection

Eleven subjects who presented with a clinical illness characteristic of primary HIV-1 infection were treated with 1 g zidovudine daily for a median period of 56 days (range, 28–111 days). Primary HIV-1 infection was confirmed in each subject by seroconversion and virus isolation. The acute phase of the illness resolved a median of 4 days (range, 3–14 days) from commencement of zidovudine. Six subjects reported symptoms that may have been side-effects of zidovudine, the most common being nausea in four subjects and headache in two. Treatment was discontinued in one subject who had persistent headache and nausea. Haemoglobin, haematocrit and erythrocyte counts decreased and mean corpuscular volume increased significantly during the treatment. None of the subjects developed anaemia and none required dose modification or blood transfusion as a result of haematological side-effects. There were no significant differences in the granulocyte count or the lymphocyte count during any week of treatment when compared with baseline levels. There were no significant differences in T-cell subset numbers of the subjects during treatment compared with a group of historical controls. HIV-1 was isolated from several subjects during and after termination of zidovudine treatment. The results of this investigation indicate that zidovudine is a safe drug to administer to people with primary HIV-1 infection. There was no clear evidence, however, of any clinical benefit in terms of resolution of the acute illness and no indication that the treatment would prevent development of persistent infection. Nevertheless, the results urge the establishment of a placebo-controlled trial to further evaluate this treatment and its effect on long-term outcome in people with primary HIV-1 infection.

Intramuscular versus Intradermal Administration of a Recombinant Hepatitis B Vaccine: A Comparison of Response Rates and Analysis of Factors Influencing the Antibody Response

In an open controlled study 286 health care workers in Stockholm, Sweden, received 20 micrograms of a recombinant hepatitis B vaccine (Engerix B) by the intramuscular route, and 383 2 micrograms by the intradermal route. Seroconversion to protective anti-HBs levels (anti-HBs titre greater than or equal to 10 IU/l) was achieved in 94% of the i.m. and 89% of the i.d. vaccinees. Female sex, intramuscular vaccination, young age, and being a non-smoker were associated with a higher response rate and a higher geometric mean anti-HBs titre than male sex, intradermal vaccination, old age and being a smoker. If an acceptable response rate to protective anti-HBs levels of 85% is chosen, intradermal vaccination can be used as a cost reducing strategy for all women and for non-smoking men less than 30 years of age, as estimated in a logistic regression model. Due to the variable antibody response in different individuals, post vaccination testing for anti-HBs titres is recommended in health care workers, regardless of vaccination route.

Incidence of hepatitis and seroconversion to hepatitis C virus after open-heart surgery in transfused and non-transfused patients in sweden

The transmission of non-A, non-B hepatitis (NANB)/hepatitis C virus (HCV) was studied in patients undergoing open-heart surgery and related to the reception of blood products and hospitalization and surgery per se. Posttransfusion hepatitis NANB was noticed in 17/390 (4.4%) patients receiving heterologous blood and 8/16 tested became positive for anti-HCV (Ortho HCV ELISA), all within 5 months after onset of hepatitis. Among patients with normal ALAT before surgery and during follow-up, who had received heterologous blood, 1/50 seroconverted after 6 months. This patient probably had a subclinical HCV infection, or possibly a temporary non-specific anti-HCV reactivity with a maximum optical density/cut-off ratio (OD/CO) of 1.2, whereas all posttransfusion hepatitis C cases had OD/CO ratios greater than 4. No hepatitis occurred among the 92 non-transfused patients and no seroconversion was found in any of 62 non-transfused patients tested 6 months after the operation. It was concluded that (1) hospitalization and surgery per se does not seem to offer a risk of hepatitis NANB/C, and (2) seroconversion to for HCV occurs in only 50% of Swedish patients with acute posttransfusion NANB hepatitis.

Prevention of Hepatitis B by immunization of the Newborn Infant a Long-term Follow-up Study in Stockholm, Sweden

In order to assess the present hepatitis B immunization program in Stockholm, Sweden, 212 children of HBsAg carrier mothers were followed up 2-9 years after birth. In babies of HBeAg-positive mothers a combined passive and active immunization schedule with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine was used. Among 25 children to such mothers, 1 HBsAg carrier and 5 children with asymptomatic seroconversion were found. To newborns of HBeAg-negative/anti-HBe-negative mothers, only vaccine was given. Among 15 such children, no HBsAg carrier (but 1 child with an asymptomatic seroconversion) was found. In babies of HBeAg-negative/anti-HBe-positive mothers, immunization was withheld between 1983 and 1987. Among 90 such children, 1 HBsAg carrier and 8 asymptomatic seroconversions were detected. After 1987, newborns in this group were vaccinated whereafter 3 asymptomatic seroconversions were found among 82 children. We conclude that in low prevalence areas a screening program for HBsAg should be offered to pregnant women originating from hepatitis B endemic regions, since immunoprophylaxis gave long-term protection to most children at risk. Children born to HBeAg-positive mothers should receive vaccine in combination with HBIg, whereas for children of mothers lacking HBeAg, vaccination only seems sufficient, at least if a rapid vaccination schedule is used.

Serum ALT levels as a surrogate marker for serum HBV DNA levels in HBeAg-negative pregnant women.

In Stockholm, Sweden, the majority of pregnant women positive for hepatitis B surface antigen (HBsAg) are hepatitis Be antigen (HBeAg) negative. Newborns to HBeAg positive mothers receive vaccination and hepatitis B immunoglobulin (HBIg). Newborns to HBeAg negative mothers receive vaccine and HBIg only if the mothers have elevated ALT levels. The aim of this study was to retrospectively evaluate ALT levels as a surrogate marker for HBV DNA levels in HBeAg negative carrier mothers. Altogether 8947 pregnant women were screened for HBV markers from 1999 to 2001 at the Virology Department, Karolinska Hospital. Among mothers screened 192 tested positive for HBsAg (2.2%). 13 of these samples could not be retrieved. Of the remaining 179 sera, 8 (4%) tested positive for HBeAg and 171 (95.5%) were HBeAg negative. Among the HBeAg negative mothers, 9 had HBV DNA levels >105copies/ml, and of these 7 had normal ALT levels indicating low sensitivity of an elevated ALT level as a surrogate marker for high HBV DNA level. Furthermore, no correlation was found between ALT and HBV DNA levels. Hence, it is concluded that the use of ALT as a surrogate marker for high viral replication in HBeAg negative mothers could be questioned.

The Introduction of HIV during 1979–80 in a Sexually Active Homosexual Population of Stockholm

Serological tests for hepatitis A (HA) and B (HB), syphilis and HIV were performed on blood samples from 3 groups of homosexual men: 220 and 124 asymptomatic men being investigated in 1978 and 1980 respectively and another 98 men suffering from HA during the winter 1979-80. The two asymptomatic groups revealed similar test results with respect to HA, HB and syphilis: about 25% had markers for HA, 50% for HB and 10-16% for syphilis. The 1979-80 HA group had a comparatively high frequency of markers for HB (64%) and for syphilis (34%), indicating that these men were sexually highly active. While all of the men in the 1978 test group were free from HIV antibodies, 2% of the 1980 and 6% of the 1979-80 group had antibodies to the virus. The results indicate that HIV was introduced to the gay population of Stockholm during 1979-80.

Prevalence of Hepatitis B Virus Markers in Icelandic Outpatients and Hospital Personnel in 1979 and in 1987

The prevalence of hepatitis B virus (HBV) infections in Iceland was investigated in 619 outpatients and 72 hospital personnel in 1979 and in 445 outpatients and 284 hospital personnel in 1987 by anti-HBc testing. The overall prevalence of anti-HBc among outpatients remained almost unchanged and was 5.7% in 1979 and 5.4% in 1987. In 1987 the prevalence rate in outpatients increased significantly from 0% in persons less than 20 years to 9.8% in persons greater than 60 years (p = 0.008). Among hospital personnel tested in 1987 the prevalence rate also increased significantly with age from 4% in those 20-29 years of age to 26% in those greater than 60 years (p = 0.024). A significant increase of the prevalence rate with years of employment was, however, not found. Laboratory technicians with frequent blood contacts had a significantly higher prevalence rate than other health care workers and outpatients tested in 1987 (p less than 0.001). Laboratory technicians had an annual attack rate of HBV infection of 1.4% from 1979 to 1987. The results indicate that the prevalence of HBV infection in 1979 and 1987 has remained unchanged in the general population and that hospital personnel exposed to blood are at increased risk of getting HBV infection.

Viral Etiology in Myasthenia gravis

Thymic cells from 26 myasthenia gravis patients were investigated by viral isolation using inoculation of supernatants obtained from thymic tissue homogenates into human and monkey cells. Living cells