Correlation between susceptibility of primary HIV-1 isolates to autologous and heterologous neutralizing antibodies. Hospital Evandro Chagas AIDS Clinical Research Group.

OBJECTIVE: To study the susceptibility of primary HIV-1 isolates towards autologous and heterologous neutralizing antibodies (NAb). DESIGN: Blood was collected and primary HIV-1 isolated from individuals residing in Rio de Janeiro, Brazil, in all phases of disease. METHODS: Primary HIV-1 isolates were incubated with autologous or heterologous plasma and neutralization of infection of freshly pre-stimulated normal human peripheral blood mononuclear cells was assayed in parallel to median infectious dose determinations in the absence of antibodies. Levels of HIV-1 p24 antigen were used for evaluation of viral neutralization. RESULTS: Autologous neutralization (75%) was observed for 13 (52%) out of 25 of the primary HIV-1 isolates, and 15 (71%) out of 21 isolates were susceptible to 75% heterologous neutralization by at least one-half of the heterologous plasma tested. Primary HIV-1 isolates susceptible to autologous NAb showed a higher susceptibility towards neutralization by heterologous NAb than isolates that could not be neutralized by the autologous plasma (P = 0.049). The susceptibility of the primary HIV-1 isolates towards neutralization by heterologous NAb was significantly higher for isolates derived from men (P = 0.001), and for isolates obtained from individuals infected through homo-/bisexual risk behaviour in comparison with those infected through heterosexual HIV-1 transmission (P = 0.03). CONCLUSIONS: Susceptibility of primary HIV-1 isolates to autologous and heterologous neutralization was significantly correlated, indicating that escape mutants may become resistant not only to autologous but also to heterologous NAb.

Anti-HIV-1 seroreactivity and HIV transmission route[R1]. The HEC/FIOCRUZ AIDS Clinical Research Group.

BACKGROUND: Antibody binding assays carried out by our group have consistently indicated a higher reactivity of sera from male HIV-1 infected individuals. This study was carried out in order to analyze the importance of gender, route of transmission, disease progression and HIV-1 genotype in seroreactivity assays. STUDY DESIGN: Specificity of antibody binding was studied in plasma of 247 HIV-1 seropositive individuals belonging to patient groups of pregnant women, injecting drug users (IDUs) and recent seroconvertors, resident in Rio de Janeiro, RJ. Recognition of synthetic peptides corresponding to antigenically important epitopes in the envelope of HIV-1 (gp41 immunodominant epitope, V3 loop, V2 loop and gp41 735-752 epitope) was determined. RESULTS: The immunodominant gp41 peptide (amino acids 594-613, HIV-1 MN sequence) was recognized by 85% of all plasma tested. Reactivity with the gp41 735-752 peptide and gp120 V2 loop peptides was low but quite variable, being generally more often specific to a Brazilian V2 peptide used than to the HIV-1 MN derived V2 peptide. The overall recognition of the different V3 peptides tested varied from 41 to 76%. Patients with more advanced disease showed a more frequent reactivity with the peptides studied than did asymptomatic patients. Statistically significant differences in peptide recognition were observed by multiple logistic analyses comparing plasma derived from individuals infected by blood or sexual HIV transmission, adjusting for disease progression and gender. Plasma from individuals infected by sexual transmission showed lower peptide recognition than did plasma from individuals infected through HIV positive blood. Association attempts between seroreactivity and genotype indicated that plasma derived from patients infected with HIV-1 of the F subtype showed highest recognition of heterologous V3 peptides, as well as a slightly more frequent recognition of the non-V3 peptides tested. Recognition of homologous peptides was generally higher than recognition of heterologous peptides. Differences were most pronounced between the prototypical HIV-1 B subtype and the Brazilian B" variant of this subtype but almost non-existent between the HIV-1 B and F subtypes. CONCLUSIONS: Individual gender was shown to be a confounder when investigating the relationships of peptide reaction to HIV-1 route of transmission through multivariate statistical methods: patients infected by blood transmission (IDU) present higher frequency of peptide recognition than individuals infected by sexual HIV-1 transmission. Plasma from individuals infected with the B" variant (GWG) of B subtype HIV-1 showed lower heterologous peptide recognition than that from HIV-1 B (GPG) or F infected individuals.

Vertical HIV-1 transmission: importance of neutralizing antibody titer and specificity.

Neutralization analyses were carried out with plasma from 132 volunteer human immunodeficiency virus (HIV)-1 infected women (76% pregnant, 24% with infants suspected for HIV-1 infection) collected between 1994 and 1998, against autologous and heterologous primary- and the reference HIV-1 MN isolates. A significantly lower percentage of HIV-1 transmissions was observed after 1996, parallel to a more intense antiretroviral treatment of infected pregnant women. HIV-1 isolation was significantly more frequent from peripheral blood mononuclear cells of mothers of infected children than mothers of uninfected children (P = 0.0065). Neutralization of autologous HIV-1 isolates was comparable for HIV-1 transmitters and nontransmitters' plasma, whereas neutralization of the reference isolate HIV-1 MN was more frequent at high titers for pregnant women who did not transmit HIV to their offspring compared to pregnant women who did. Although neutralization of heterologous primary HIV-1 isolates from HIV transmitters and non transmitters by transmitter plasma occurred with similar frequency, neutralization of isolates from transmitters was much more frequent when heterologous plasma from nontransmitters were used. Macrophage-tropic heterologous HIV-1 isolates were neutralized more frequently at higher titers by plasma from nontransmitters than from transmitters. The results obtained indicate that antiretroviral treatment, lack of success of HIV-1 isolation and high titers of antibodies able to neutralize macrophage-tropic viruses appear to be of importance for protection against HIV-1 vertical transmission for the group of patients studied.

Neutralization susceptibility of B subtype variant B" primary HIV-1 isolates. The HEC/FIOCRUZ AIDS Clinical Research Group.

Susceptibility to autologous and heterologous neutralization of primary human immunodeficiency virus (HIV)-1 isolates belonging to subtype B, to the B"-variant of subtype B or to subtype F from infected individuals residing in Rio de Janeiro was assayed. A lower infectivity of the B"- and F isolates when compared to the classical B-subtype HIV-1 isolates was observed. Comparisons of neutralization susceptibilities were carried out for 19 B-subtype, 11 B"-variant and two F-subtype HIV-1 isolates with plasma from autologous and heterologous samples. Frequency of autologous neutralization was slightly lower for B-subtype isolates in comparison to B"-variant isolates. Heterologous intra-subtype neutralization was significantly lower for B-subtype than for the B"-variant or the F-subtype isolates. While B-subtype isolates were neutralized by most anti-F-subtype plasma, F-subtype isolates, although most susceptible to F-subtype antibodies, were highly susceptible to neutralization by anti-B-subtype antibodies. Cross-neutralization for B"-variant and B-subtype isolates was not as extensive as observed for B- and F-subtype isolates. However, the results presented indicate a quite extensive cross-neutralization between Brazilian HIV-1 isolates.

HIV specific humoral immune response in Rio de Janeiro, Brazil. The HEC/Fiocruz AIDS Clinical Research Group.

Efforts to characterize HIV-1 polymorphism and anti-HIV immune response are being made in areas where anti-HIV/AIDS vaccines are to be employed. Anti-HIV-1 humoral immune response is being studied in infected individuals residents in Rio de Janeiro, in distinct cohorts involving recent seroconvertors, pregnant women or intravenous drug users (IDU). Comparative analyses of specificity of antibody response towards epitopes important for anti-HIV-1 immune response indicate quantitative differences between cohorts, with an exceptionally strong response in IDUs and weakest response in pregnant women. However, a comparative analysis between pregnant women cohorts from Rio de Janeiro and Rio Grande do Sul indicated an even lower response (with exception of the anti-V3-C clade peptide recognition) for the southern cohort. Studies analysing the immune function of the humoral response indicate a quite elevated occurrence of antibodies capable for neutralizing heterologous primary HIV-1 isolates from Rio de Janeiro. Attempts to correlate seroreactivity with HIV-1 neutralization with respect to HIV-1 polymorphism were not very successful: while the Brazilian B clade B " variant could be recognized by binding assays, no significant distinction of HIV-1 clades/variants was observed in viral neutralization assays.

HIV specific humoral immune response in Rio de Janeiro, Brazil

Efforts to characterize HIV-1 polymorphism and anti-HIV immune response are being made in areas where anti-HIV/AIDS vaccines are to be employed. Anti-HIV-1 humoral immune response is being studied in infected individuals resident in Rio de Janeiro, in distinct cohorts involving recent seroconvertors, pregnant women or intravenous drug users (IDU). Comparative analysis of specificity of antibody response towards epitopes important for anti-HIV-1 immune response indicate quantitative differences between cohorts, with an exceptionally strong response in IDUs and weakest response in pregnant women. However, a comparative analysis between pregnant women cohorts from Rio de Janeiro and Rio Grande do Sul indicated an even lower response (with exception of the anti-V3-C clade peptide recognition) for the southern cohort. Studied analysing the immune function of the humoral response indicate a quite elevated occurrence of antibodies capable of neutralizing heterologous primary HIV-1 isolates from Rio de Janeiro. Attempts to correlate seroreactivity with HIV-1 neutralization with respect to HIV-1 polymorphism were not very successfull: while the Brazilian B clade B" variant could be recognized by binding assays, no significant distinction of HIV-1 clades/variants was observed in viral neutralization assays.