Slow Acceptance of Universal Antiretroviral Therapy (ART) Among Mothers Enrolled in IMPAACT PROMISE Studies Across the Globe.

The PROMISE trial enrolled asymptomatic HIV-infected pregnant and postpartum women not eligible for antiretroviral treatment (ART) per local guidelines and randomly assigned proven antiretroviral strategies to assess relative efficacy for perinatal prevention plus maternal/infant safety and maternal health. The START study subsequently demonstrated clear benefit in initiating ART regardless of CD4 count. Active PROMISE participants were informed of results and women not receiving ART were strongly recommended to immediately initiate treatment to optimize their own health. We recorded their decision and the primary reason given for accepting or rejecting the universal ART offer after receiving the START information. One-third of participants did not initiate ART after the initial session, wanting more time to consider. Six sessions were required to attain 95% uptake. The slow uptake of universal ART highlights the need to prepare individuals and sensitize communities regarding the personal and population benefits of the "Treat All" strategy.

Seroprevalence of HPV vaccine types 6, 11, 16 and 18 in HIV-infected and uninfected women from Brazil.

BACKGROUND: Information on vaccine-type HPV seroprevalence is essential for vaccine strategies; however, limited data are available on past exposure to HPV-quadrivalent vaccine types in HIV-infected woman in Brazil. OBJECTIVES: To assess the seroprevalence for HPV types 6, 11, 16 and 18 in HIV-infected and uninfected women, from Rio de Janeiro, Brazil and to investigate potential associations with age and pregnancy status. STUDY-DESIGN: 1100-sera were tested by virus-like particle (VLPs)-based ELISA for antibodies to HPV types 16, 18, 6 and 11. Statistical analysis was carried out by STATA/SE 10.1 and comparisons among HIV-infected and HIV-uninfected women were assessed by Poisson regression models with robust variance. RESULTS: HPV-6, 11, 16 and 18 seroprevalence was significantly higher among HIV-positive women (29.9%, 8.5%, 56.2% and 38.0%, respectively) compared to HIV-negative women (10.9%, 3.5%, 30.8% and 21.7%, respectively), when adjusted by age and pregnancy status. Overall, 69.4% of HIV-infected and 41.5% of HIV-uninfected women tested positive for any HPV quadrivalent vaccine type. However 4.7% and 1.1%, respectively, tested positive for all HPV vaccine type. In HIV-uninfected women who were pregnant, we found a higher HPV-11 seroprevalence (8.5% vs. 1.5%; P < 0.001) and a lower HPV 16 seroprevalence (22.6% vs. 34.2%; P = 0.010) compared to not pregnant women. HIV-uninfected women, aged 40 or more years old had a higher HPV 16 seroprevalence compared to women aged less than 40 years old. CONCLUSIONS: We did not observe a strong association between age and positive HPV antibodies nor an association between pregnancy and HPV seroprevalence. HPV seroprevalence was significantly higher among HIV-infected women compared to HIV negative women. In both populations the seroprevalence to all four HPV vaccine types was low suggesting that women may potentially benefit from the HPV vaccines.

Supporting adherence to highly active antiretroviral therapy and protected sex among people living with HIV/AIDS: the role of patient-provider communication in Rio de Janeiro, Brazil.

This exploratory study examined patient-provider communication dynamics regarding adherence to highly active antiretroviral therapy (HAART) and protective sexual behavior among people living with HIV/AIDS (PLWHA). We conducted 20 direct observations of routine consultations between PLWHA and care providers in two large public health clinics providing free HIV medications and clinical care to PLWHA in the greater Rio de Janeiro area of Brazil. Immediately after these observations, 20 semistructured in-depth interviews were conducted with observation participants regarding their communication with providers, overall clinic experience, and questions and concerns about adherence to HAART and safe sex. Findings from observations showed that patient-provider communication focused almost exclusively on biomedical aspects of HIV-related treatment such as symptom management. In most observations, adherence to HAART was addressed. However, questions posed by providers regarding adherence were generally close-ended and leading, discouraging an open exchange regarding potential difficulties related to adherence. HIV/sexually transmitted infection (STI)- related protective behaviors were seldom addressed except when the patient displayed STI symptoms or was thought to be pregnant. In qualitative interviews, patients generally reported satisfaction with their providers, but also reported a variety of concerns and challenges related to adherence to HAART and protective sexual behavior that were not expressed in patient-provider interactions. We conclude that one way in which adherence to HAART and protective sexual behavior among PLWHA could be facilitated is by improving patient- provider communication on these topics, including increasing the frequency of openended, nonjudgmental dialogue initiated by care providers.

The search for social validation and the sexual behavior of people living with HIV in Rio de Janeiro, Brazil: understanding the role of treatment optimism in context.

The primary aim of this qualitative study was to explore the influence of HIV treatment optimism on the sexual behavior of people living with HIV/AIDS (PLWHA) receiving highly active anti-retroviral therapy (HAART) at public health clinics in Rio de Janeiro, Brazil. We also explored the psycho-social dynamics of participants' sexual relationships in order to understand more broadly how these factors influence the sexual behavior of PLWHA and how they shape HAART-related beliefs. Twenty-three semi-structured, in-depth interviews were conducted with three groups: heterosexual women, heterosexual men and men who have sex with men living with HIV who reported being sexually active in the last year and were currently receiving HAART. We found that the availability of HAART was conceptualized as a rationale for unsafe sex among a minority of study participants and that this was more common among men than among women. Specific examples of treatment optimism appeared to be employed as a means to avoid acknowledging how deeper psychosocial issues may have been influencing participant's sexual behavior. Most participants' sexual behavior appeared largely to be a product of their desire for social validation and linked to feelings of shame and denial, including but not limited to HIV. Participants from all three groups expressed a considerable amount of fear and/or anxiety regarding behaviors such as disclosure and condom use as a result of the unexplored conflict between implementing these behaviors and continuing with their strategies for social validation within the context of their sexual relationships. We conclude that short-term information, education and communication interventions surrounding treatment optimism, disclosure and condom use are appropriate and necessary; but that they are not sufficient to address the core challenges to unsafe sex among PLHWA. These deep-rooted psychosocial issues may be better addressed by longer-term individual and group-level opportunities for exploration and critical reflection regarding sense of self and its relationship to social solidarity among PLWHA.

Human immunodeficiency virus type 1 neutralization by plasma from B or F genotype infected individuals.

Anti-human immunodeficiency virus type 1 (HIV-1) "binding antibodies" (antibodies capable of binding to synthetic peptides or proteins) occur throughout HIV-1 infection, are high-titered and highly cross-reactive, as confirmed in this study by analyzing plasma from B and F genotype HIV-1 infected individuals. Plasma from individuals infected with clade F HIV-1 displayed the most frequent cross-reactivity, in high titers, while Bbr plasma showed much higher specificity. Similarly, neutralization of a reference HIV-1 isolate (HIV-1 MN) was more frequently observed by plasma from F than B genotype infected individuals. No significant difference was seen in neutralization susceptibility of primary B, Bbr or F clade HIV-1 by plasma from individuals infected with the classical B (GPGR) or F HIV-1, but Bbr (GWGR) plasma were less likely to neutralize the F genotype primary HIV-1 isolates. The data indicate that both B and F genotype derived vaccines would be equally effective against B and F HIV-1 infection, with a slightly more probable effectiveness for F than B genotype. Although the Bbr variant appears to induce a much more specific humoral immune response, the susceptibility in neutralizing the Brazilian HIV-1 B genotype Bbr variant is similar to that observed with the classical B genotype HIV-1.

Neutralization titres and vertical HIV-1 transmission.

Replication of the human immunodeficiency virus type 1 (HIV-1) isolate MN in CEM cells was less neutralized by the plasma from the mothers of infected children (MIC) in comparison with the plasma from the mothers of uninfected children (MUC). Significantly higher neutralization titres were observed for the sera from MUCs compared with MICs, and only the sera from MUC showed 100% neutralization of the HIV-1 MN strain. We suggest that a simple neutralization assay as described here could be useful in prognostic analyses.

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.

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.

Spectrum of morphologic changes of lymph nodes in HIV infection.

Cervical lymph nodes biopsies from 31 HIV positive patients (with or without AIDS) were studied by histologic methods and immunohistochemistry (StreptABC staining of paraffin sections) to identify cellular and extracellular matrix components. The results were the following: (1) the biopsies were included in the stages of follicular hyperplasia without fragmentation FH-FF (4 cases); follicular hyperplasia with follicular fragmentation FH + FF (16 cases); follicular involution FI (6 cases) and diffuse pattern DP (5 cases); (2) the most important alteration was the germinal centers disruption due to follicle lysis, which began in the light zone; (3) there was coincidence between intrafollicular hemorrhages and segmental hyaline mycroangiopathy; (4) during the progression of the disease occurred; (a) an increase in the number of mast cells, CD68+ and Mac 387+ macrophages; (b) a diffuse augment of collagen III, elastic fibers, laminin, fibronectin and proteoglycans; (c) maintenance of Factor VIII-related antigens in the vascular endothelial cells, with decrease in the expression of Ulex-Europeus I lectin. Follicular hyperplasia (FH - FF or FH + FF) was the most common histologic pattern recognized in the lymph nodes of patients without AIDS and follicular involution and difuse pattern were seen in those who had AIDS. The results indicate that the lymph node biopsies may provide important information about the evolutive stage of the disease and its prognosis.