Örjan Strannegård

Antigen detection in primary HIV infection.

Serial blood samples were obtained from 21 homosexuals who had developed symptomatic primary infection with human immunodeficiency virus (HIV) after a median incubation time of 14 days. During the first two weeks after the onset of illness HIV antigen (p24) was detected in the blood by enzyme linked immunosorbent assay (ELISA). During the second and third weeks after the onset of illness p24 antibody was detected by Western blot assay and antigen concentrations rapidly decreased to undetectable values. Dissociation of antigen-antibody complexes showed complexed antigen during the phase of declining concentrations of free antigen. Neither free nor complexed antigen was detected in any serum samples for several months thereafter, which suggested that failure to detect HIV antigen reflected low or absent synthesis of viral protein rather than masking of antigen by antibodies. Reappearance of HIV antigen with a fall in p24 antibody concentration was observed in a few patients six months or more after the onset of disease. The combined use of antigen and antibody assays made it possible to obtain evidence of infection with HIV in all of the 95 serum samples tested, illustrating the usefulness of these assays for diagnosing infection with HIV in its early stages.

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.

Human immunodeficiency virus infection of the brain: I. Virus isolation and detection of HIV specific antibodies in the cerebrospinal fluid of patients with varying clinical conditions

Isolation of the human immunodeficiency virus (HIV) has been attempted from the cerebrospinal fluid (CSF) of 29 subjects with varying severity of HIV infection. Virus could be isolated from patients in all stages of disease including patients with primary HIV infection and asymptomatic carriers. In the early stages of infection free virus was infrequently present in the CSF but could be isolated from the cells present in CSF. This suggests that HIV may reach the brain at a very early stage of infection and that initially there is little production of virus from infected cells. In the late stages of HIV infection, associated with increasing severity of immunodeficiency, free virus could readily be isolated from the CSF. With one exception, all of these patients had neurological and/or psychiatric symptoms, as compared to only 2 (of 13) subjects in the early stages of infection. All patients with HIV-specific antibodies in serum had antibodies also in CSF. Examined by a radioimmunoprecipitation assay, CSF was more often found to contain antibodies to the precursor (p55) of viral core proteins than the corresponding serum of the patients. We propose that immune disturbances have an essential pathogenic role in the neurological/psychiatric symptoms associated with HIV infection, possibly through allowing increased viral expression in the central nervous system.

Hepatitis C virus infection in individuals with or without human immunodeficiency virus type 1 infection

SummarySerum specimens from 111 human immunodeficiency virus type 1 (HIV-1) infected and 183 HIV-1 seronegative patients were analysed for antibodies to hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis A virus (HAV) by enzyme linked immunoassay (ELISA) and radioimmunoassay. Anti-HCV and anti-HBV antibodies were found in the vast majority (89 and 83%, respectively) of intravenous drug addicts (IVDA), independent of the type of drug abuse or whether the patients were HIV-1 infected or not. Anti-HAV antibodies were found in 60% of the IVDA. Anti-HCV antibodies were found in anti-HIV-1 positive homosexual men (14%) and anti-HIV-1 negative heterosexual persons (8%), but not in HIV-1 seronegative homosexual men. Also anti-HAV antibodies were found to a small extent in these groups. In contrast, anti-HBV antibodies were common in the homosexual men. The absorbance values of the positive reactions in the anti-HCV ELISA were lower for HIV-1 seropositive patients than those for HIV-1 seronegative subjects, particularly in the late stages of HIV-1 infection. These data suggest that HCV infection is transmitted as readily as HBV infection by intravenous drug abuse and that all three types of hepatitis virus infection are common in IVDA. Although transmission of HCV is primarily mediated by blood, sexual transmission may also occur. HIV-1 infection seems to be associated with unusually low levels of anti-HCV antibodies, especially in the late stages of HIV-1 infection.ZusammenfassungSerumproben von 111 mit dem menschlichen Immunschwächevirus Typ 1 (HIV-1) Infizierten und von 183 HIV-1 seronegativen Patienten wurden auf Antikörper gegen das Hepatitis C Virus (HCV), Hepatitis B Virus (HBV) und Hepatitis A Virus (HAV) mittels enzymgebundenem Immunassay (ELISA) oder Radioimmunassay untersucht. Bei der überwiegenden Mehrzahl der i. v. Drogenabhängigen fanden sich Antikörper gegen HCV (89%) und HBV (83%). Dabei fand sich keine Korrelation zur Art der Droge oder HIV-Infektion. 60% der i. v. Drogenabhängigen hatten auch HAV-Antikörper. Unter den anti-HIV-1 positiven Männern wiesen 14% Antikörper gegen HCV auf. Anti-HIV negative heterosexuelle Personen waren zu 8% anti-HCV positiv. Unter den HIV-1 seronegativen homosexuellen Männern fanden sich in keinem Fall Antikörper gegen HCV. Ein kleiner Anteil der Personen dieser Gruppen wies auch Antikörper gegen HAV auf. Anti-HBV Antikörper fanden sich häufig bei homosexuellen Männern, wobei keine Abhängigkeit vom HIV-Serumstatus bestand. Bei HIV-1 seropositiven Patienten, und zwar besonders ausgeprägt im Spätstadium der HIV-Infektionen, waren die Absorptionswerte bei positivem anti-HCV ELISA niedriger als bei HIV-1 seronegativen Personen. Daraus läßt sich schließen, daß die HCV-Infektion wie die HBV-Infektion durch intravenösen Drogenmißbrauch übertragen wird und daß alle drei Typen der Virushepatitis bei i. v. Drogenabhängigen häufig sind. Obwohl die HCV-Übertragung hauptsächlich durch Blut erfolgt, ist eine sexuelle Übertragung ebenfalls möglich. Bei HIV-1 Infizierten sind die anti-HCV Antikörperspiegel ungewöhnlich niedrig, vor allem in den Spätstadien der Infektion.

Sequence analysis of selected regions of the env (V3 loop and gp41) and gag (p7) reading frames of Ethiopian human immunodeficiency virus type 1 strains.

SummaryAmplified polymerase chain reaction (PCR) products, corresponding to the V3 loop and gp 41 of theenv, and p 7 of thegag region, from proviral DNA of several Ethiopian and Swedish HIV-1 strains were sequenced. Of the six amino acids (GPGRAF) that constitute the principal neutralizing determinant (PND) within the V 3 loop, the Ethiopian isolates all showed two amino acid changes (GPGQTF). Four to five other substitutions were found in the amino acids flanking the PND. Substitution of alanine (A) for threonine (T) should result in a change in the predicted secondary structure, i.e., disappearance of a coil structure. Percentage similarity data on a stretch of 22 amino acids within the V 3 loop showed a concordance of the Ethiopian HIV-1 isolates with the sequences of published macrophage-T-cell tropic HIV isolates. Additionally derived protein sequences in two other regions showed two common substitutions in p 7 and one to two substitutions in gp 41 compared to a recent consensus sequence. These changes are hitherto unique for the Ethiopian strains, and suggest the presence of a clustering of a divergent HIV-1 strain in Addis Ababa, Ethiopia.

HIV-1 in Ethiopia : phylogenetic divergence from other HIV-1 strains

Phylogenetic tree analysis was performed on selected polymerase chain reaction (PCR)-amplified and sequenced regions of the gag and env reading frames of several Ethiopian and Swedish human immunodeficiency virus type 1 (HIV-1) strains. These regions are considered to be conserved parts of the HIV-1 genome and correspond to the p7 of the core (gag) and part of the carboxy terminal of the gp41 protein of env respectively. Comparisons were made with all available HIV-1 sequences.The tree analysis showed that gag sequences from nine and env sequences from four Ethiopian strains all grouped together in separate branches distinct from all other sequenced European, North American, and African HIV-1 isolates. Thus, the Ethiopian strains seem to represent a highly divergent group of HIV-1, which might have developed during a relatively early stage of HIV-1 evolution.