Inhibition of purified recombinant reverse transcriptase from wild-type and zidovudine-resistant clinical isolates of human immunodeficiency virus type 1 by zidovudine, stavudine, and lamivudine triphosphates.

Cross-resistance between zidovudine, stavudine, and lamivudine was studied, using purified recombinant reverse transcriptase from a zidovudine-susceptible and -resistant pair of clinical isolates of human immunodeficiency virus type 1. The zidovudine-resistant isolate exhibited low-level cross-resistance to both stavudine and lamivudine in drug susceptibility assays. Enzyme from the resistant isolate demonstrated reduced inhibition by zidovudine triphosphate and stavudine triphosphate and, to a lesser extent, lamivudine triphosphate. These findings provide additional evidence at the viral and enzyme level for cross-resistance between zidovudine and stavudine, and they suggest a possible effect of zidovudine resistance on susceptibility to lamivudine.

Inactivated pronase as the cause of false-positive results of serum cryptococcal antigen tests.

Four patients who had acquired immunodeficiency syndrome and who were evaluated for headache within a 3-week period had false-positive results of serum cryptococcal antigen tests. This cluster of false-positive test results appeared to be due to inactivation of the pronase vial in the test kit, a cause that has not been reported previously.

Molecular epidemiology of HIV-1 in Switzerland: evidence for a silent mutation in the C2V3 region distinguishing intravenous drug users from homosexual men. Swiss HIV Cohort Study.

OBJECTIVES: To study the molecular epidemiology of HIV-1 strains found in Switzerland and to determine possible genetic linkages among strains sorted by risk group or geographic region. DESIGN: A cross-sectional, clinic-based survey of HIV-1 molecular sequences and linked patient history from Swiss people. METHODS: Specimens were collected from 215 HIV-1-infected people in HIV outpatient clinics of four tertiary referral centers (Lausanne, St. Gallen, Zurich, and Basel) between May and August 1996, mainly from homosexual men, injecting drug users (IDU), and heterosexually infected people. In addition, specimens collected between 1991 and 1995 in the HIV outpatient clinic at University of Geneva were included into this survey. These specimens were collected primarily for an ongoing, prospective cohort (Swiss HIV Cohort Study). Direct C2V3C3 sequences of the env gene were determined from 158 samples of peripheral blood mononuclear cells. Genetic data were analyzed with the available patient history on each specimen. RESULTS: As found in other previous studies in Europe, primarily subtype B viruses were identified, whereas seven (4%) of 158 were non-subtype B: one subtype D, four subtype A, and two subtype E. Five of seven non-B subtypes occurred in immigrants from African or Asian countries and all seven were found exclusively in individuals who had been infected by heterosexual contact. No significant clustering of strains within different study sites or risk groups was found. A silent mutation (LAI env 834) occurred significantly more often in IDU than in homosexual men (p<.001). CONCLUSIONS: Although the lack of significant clustering of strains by risk group or geographic region may result from early introduction of subtype B viruses in Switzerland, the strong association of a silent mutation with IDU suggests that, early in the epidemic, there was a unique founder virus among IDUs. The HIV epidemic in Switzerland is still predominantly caused by subtype B viruses.

Subtype G and multiple forms of A/G intersubtype recombinant human immunodeficiency virus type 1 in Nigeria.

Multiple human immunodeficiency virus type 1 (HIV-1) genetic subtypes, intersubtype recombinants, and group O have been found in west central Africa. In Nigeria, where HIV-1 prevalence is rising rapidly, characterization of HIV-1 strains has been limited. Each of three full-length genome sequences acquired to date shows evidence of recombination: two are largely subtype G with subtype A segments in the midgenome accessory region; the third, IbNG, is subtype G with the long terminal repeats and two segments of pol from subtype A. In this study, peripheral blood mononuclear cells obtained in 1994-1995 from 10 patients hospitalized in northeastern Nigeria were evaluated by sequencing of the complete envelope and, from 7 patients, a portion of gag. Four patients harbored subtype G viruses and six patients had recombinant viruses. Two had strains sharing the A/G recombinant structure of IbNG. Two had a previously undescribed recombinant, mostly subtype A, whose carboxyl-terminal gp41 could not be classified. An A/G recombinant different from IbNG but similar to CA1, a Cameroonian strain, was found in one patient. The remaining patient had a strain that was otherwise subtype G but shared an unclassified carboxyl-terminal gp41 segment with the CA1-like strains. Other subtypes and group O were not found.

Comparison of chemotaxis and superoxide generation of indium-111-oxine- and technetium-99m-HMPAO-labelled granulocytes.

The diagnostic value of imaging infection with labelled granulocytes depends on the functional integrity of the reinfused cells. The aim of this study was to compare the functional integrity of granulocytes labelled with indium-111-oxine and technetium-99m-hexamethylpropyleneamineoxime (HMPAO), respectively, in comparison to unlabelled control granulocytes. Granulocytes were purified from healthy subjects and labelled with either 111In-oxine or 99mTc-HMPAO. Chemotaxis and superoxide production induced by formyl-peptide and phorbol-myristate-acetate were measured. Granulocytes labelled with 111In-oxine had significantly (p < 0.001) decreased chemotaxis. Superoxide production of granulocytes stimulated with phorbol-myristate-acetate showed no significant difference between control cells and those labelled using either technique. In contrast, formyl-peptide-stimulated superoxide production was increased in granulocytes labelled with 111In-oxine (p < 0.01) and in cells labelled with 99mTc-HMPAO (p < 0.03), indicating a priming compared to unlabelled cells. In conclusion, 99mTc-HMPAO-labelled granulocytes show biological properties superior to 111In-oxine-labelled cells, and should therefore be favoured for use in leucocyte labelling and infectious disease imaging.