Sylvia Lopes Maia Teixeira

The role of "long-term" and "new" injectors in a declining HIV/AIDS epidemic in Rio de Janeiro, Brazil.

Background. A substantial decline of HIV prevalence has been observed in injection drug users (IDUs) from Rio de Janeiro, in recent years. Differential characteristics and behaviors of new (injecting for <6 years) and long-term (>=6 y) injectors may help to understand recent changes and to implement appropriate preven-tion strategies. Methods. Between October 1999 and December 2001, 609 active/ex-IDUs were recruited from different communities, interviewed, and tested for HIV. Contingency table analysis and t-tests were used to assess differences between new and long-term injectors. Multiple logistic regression was used to identify independent predictors of HIV serostatus for long-term and new injectors. Results. HIV prevalence was 11.7% for 309 long-term injectors (95% CI 8.1–15.3) and 4.3% for 300 new injectors (95% CI 2.0–6.6). New injectors reported having engaged in treatment and having received syringes from needle exchange programs (NEPs) more frequently than long-term injectors in the last 6 months, but sharing behaviors remained frequent and even increased vis-à-vis long-term injectors. For male new injectors, “sexual intercourse with another man” was found to be the sole significant risk factor for HIV infection (Adj OR = 8.03; 95% CI 1.52–42.48). Among male long-term injectors, “to have ever injected with anyone infected with HIV” (Adj OR = 3.91; 95% CI 1.09–14.06) and to have “ever been in prison” (Adj OR = 2.56; 95% CI 1.05–6.24) were found to be significantly associated with HIV infection. Discussion. New injectors are seeking help in drug treatment centers or needle exchange programs. They differ from long-term injectors in terms of their risk factors for HIV infection and have lower prevalence levels for HIV. Such differences may help to understand the recent dynamics of HIV/AIDS in this population and highlight the need to reinforce new injectors’ help-seeking behavior and to reduce current unacceptably high levels of unprotected sex and syringe sharing in new injectors despite attendance of prevention/treatment programs.

Lack of Primary Mutations Associated With Integrase Inhibitors Among Hiv-1 Subtypes B, C, and F Circulating in Brazil

Background:Antiretroviral drugs targeting integrase (IN) have recently been approved for use in combined and salvage therapeutic interventions. Objective:To evaluate the presence of natural polymorphisms and resistance mutations associated with IN inhibitors among HIV-1 subtypes B, C, and F samples obtained from drug-naive individuals and patients failing highly active antiretroviral therapy in Brazil. Methods:Proviral DNA was obtained from blood samples of 105 HIV-1-positive drug-naive patients infected by B, C, or F subtypes and plasma viral RNA from 30 subtype B-infected individuals failing highly active antiretroviral therapy. The IN region was amplified by nested polymerase chain reaction and automatically sequenced for subtype determination. Translated amino acid sequences were inspected for IN mutations associated with antiretroviral resistance. Results:Eleven mutations described as conferring in vitro resistance to IN strand transfer inhibitors were detected among the HIV-1 Brazilian samples. V72I and V201I were considered as polymorphisms. Major mutations associated with elvitegravir or raltegravir in vivo resistance (Q148K/H/R, N155H) were not detected. Conclusions:Although some naturally occurring polymorphisms were observed, the absence of major resistance mutations for the current IN inhibitors provides a good rationale for the introduction of these drugs in Brazil. These results highlight the importance of the continuous surveillance of IN genetic diversity.

Is human immunodeficiency virus/acquired immunodeficiency syndrome decreasing among Brazilian injection drug users? Recent findings and how to interpret them

We briefly review findings from Brazilian settings where the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic among injection drug users (IDUs) seems to be decreasing, highlighting recent findings from Rio de Janeiro and discussing methodological alternatives. Former analyses using serologic testing algorithm for recent HIV seroconversion have shown that HIV incidence has been low in IDUs recruited by two different surveys carried out in Rio, where low injection frequencies and infection rates have been found among new injectors. The proportion of AIDS cases among IDUs in Rio has been fairly modest, compared to São Paulo and especially to the southernmost states. Notwithstanding, the interpretation of findings from serial surveys constitutes a challenge, magnified in the assessment of HIV spread among IDUs due to the dynamic nature of the drug scenes and limitations of sampling strategies targeting hard-to-reach populations. Assessment of epidemic trends may profit from the triangulation of data, but cannot avert biases associated with sampling errors. Efforts should be made to triangulate data from different sources, besides exploring specific studies from different perspectives. In an attempt to further assess the observed trends, we carried out original analyses using data from Brazilian AIDS databank.

HIV controllers with different viral load cut-off levels have distinct virologic and immunologic profiles

Background:The mechanisms behind natural control of HIV replication are still unclear, and several studies pointed that elite controllers (ECs) are a heterogeneous group. Methods:We performed analyses of virologic, genetic, and immunologic parameters of HIV-1 controllers groups: (1) ECs (viral load, <80 copies/mL); (2) ebbing elite controllers (EECs; transient viremia/blips); and viremic controllers (VCs; detectable viremia, <5000 copies/mL). Untreated noncontrollers (NCs), patients under suppressive highly active antiretroviral therapy (HAART), and HIV-1–negative individuals were analyzed as controls. Results:Total and integrated HIV-1 DNA for EC were significantly lower than for NC and HAART groups. 2-LTR circles were detected in EEC (3/5) and VC (6/7) but not in EC. Although EC and EEC maintain normal T-cell counts over time, some VC displayed negative CD4+ T-cell slopes. VC and EEC showed a higher percentage of activated CD8+ T cells and microbial translocation than HIV-1–negative controls. EC displayed a weaker Gag/Nef IFN-&ggr; T-cell response and a significantly lower proportion of anti-HIV IgG antibodies than EEC, VC, and NC groups. Conclusion:Transient/persistent low-level viremia in HIV controllers may have an impact on immunologic and virologic profiles. Classified HIV controller patients taking into account their virologic profile may decrease the heterogeneity of HIV controllers cohorts, which may help to clarify the mechanisms associated to the elite control of HIV.

Analysis of HIV-1 BF pr/rt recombinant strains from Rio de Janeiro/Brazil reveals multiple unrelated mosaic structures.

Due to the co-circulation of HIV-1 subtypes B and F1 in Brazil, a large variety of unique BF1 recombinant forms (URFs_BF1) and four circulating BF1 recombinant forms (CRF28, CRF29, CRF39 and CRF40) have been described. The aim of this study was to investigate mosaic structure and phylogenetic relationship among several BF1 (protease-reverse transcriptase, pr/rt) recombinant sequences obtained from a group of patients from Rio de Janeiro, Brazil, from 1994 to 2005. Phylogenetic relationships were estimated by Bayesian and SplitsTree methods. Recombination breakpoints were analyzed by Bootscan. Those samples presenting the same recombinant pattern in the pr/rt region were investigated in the integrase (int) and envelope (env) regions as a screening method for the detection of potential new CRFs candidates. Third out of 61 pr/rt HIV-1 BF1 recombinant sequences analyzed depicted unique recombinant structures and were classified URFs_BF1. The other 31 samples segregated in eight well-supported phylogenetic clusters composed of at least three samples sharing the same recombination pattern. Analyses of the int and env regions from these 31 samples revealed that 11 samples were URFs_BF1. Three and four sequences corresponded, respectively, to the previously described CRF39 and CRF40. Three samples displayed a CRF28-like mosaic structure, and one sample a CRF29-like mosaic pattern. The other nine BF1 samples segregate in three distinct clusters with the same recombination profile and could represent good candidates for new CRFs_BF profiles. The HIV-1 BF1 epidemic in Rio de Janeiro is characterized by a high prevalence (67%) of URFs_BF1 and a low prevalence (4.9-6.6%) of each CRFs_BF previously identified in Brazil.

HIV-1, HBV, HCV, HTLV, HPV-16/18, and Treponema pallidum infections in a sample of Brazilian men who have sex with men

Background Men who have sex with men (MSM) are more vulnerable to blood-borne infections and/or sexually-transmitted infections (STI). This study was conducted to estimate the prevalences of mono and co-infections of HIV-1 and other blood-borne/STIs in a sample of MSM in Campinas, Brazil. Methods Responding Driven Sampling (RDS) was used for recruitment of MSM. Serum samples collected from 558 MSM were analyzed for the presence of serological markers for HIV-1, HBV, HCV, HTLV, HPV-16/18, and T. pallidum infections. Results The highest prevalences of infection in serum samples were found for HPV-16 and 18 (31.9% and 20.3%, respectively). Approximately 8% of the study population showed infection with HIV-1, and within that group, 27.5% had recently become infected with HIV-1. HBV infection and syphilis were detected in 11.4% and 10% of the study population, respectively, and the rates of HTLV and HCV infection were 1.5% and 1%, respectively. With the exception of HTLV, all other studied infections were usually found as co-infections rather then mono-infections. The rates of co-infection for HCV, HPV-18, and HIV-1 were the highest among the studied infections (100%, 83%, and 85%, respectively). Interestingly, HTLV infection was usually found as a mono-infection in the study group, whereas HCV was found only as a co-infection. Conclusions The present findings highlight the need to educate the MSM population concerning their risk for STIs infections and methods of prevention. Campaigns to encourage vaccination against HBV and HPV could decrease the rates of these infections in MSM.

Distribution of CCR5 genotypes and HLA Class I B alleles in HIV-1 infected and uninfected injecting drug users from Rio de Janeiro, Brazil

Host genetic factors play an important role in the HIV epidemic dynamics, and have been considered in studies assessing susceptibility/resistance to HIV-1 infection as well as clinical evolution. Class I and Class II HLA alleles have been associated with the heterogeneity of HIV-1 infection susceptibility, as protective or risk factors for HIV-1 transmission. Moreover, a 32-base pair deletion in the HIV-1 CCR5 gene-coding region confers resistance to HIV-1 infection in homozygous individuals for the deleted allele. In this study, DNA samples from HIV-1 infected and uninfected injecting drug users (IDUs) from Rio de Janeiro were PCR amplified to determine CCR5 genotypes based on the presence of the CCR5Delta32 mutation and typed for the HLA-B locus, in an attempt to assess possible associations between these genetic factors and susceptibility/resistance to HIV-1 infection. The distribution of CCR5 genotypes between the two IDU groups did not differ. The homozygous mutant genotype Delta32/Delta32 was not found in this study. Except for HLA-B*45 (4.0% vs. 3.0%; p=0.04) and for B*51 (12.1% vs. 4.4%; p=0.002), no statistically significant differences were made evident when analyzing the frequencies of each HLA-B allele between Caucasian and non-Caucasian IDUs. The most frequent HLA-B alleles were B*15; B*35; B*44 and B*51. Although some differences in the allele frequencies could be observed between the two IDU groups, none of these was statistically significant. Therefore, no putative association between these genetic markers and susceptibility/resistance to HIV-1 infection could be made evident in the present study. So far, the assessment of genetic markers among the IDU population has been restricted to North American, European, and Asian studies and this report represents a pioneer descriptive study of the distribution of CCR5 genotypes and HLA-B alleles in Rio de Janeiro, Brazil.

Assessing the HIV-1 Epidemic in Brazilian Drug Users: A Molecular Epidemiology Approach.

Person who inject illicit substances have an important role in HIV-1 blood and sexual transmission and together with person who uses heavy non-injecting drugs may have less than optimal adherence to anti-retroviral treatment and eventually could transmit resistant HIV variants. Unfortunately, molecular biology data on such key population remain fragmentary in most low and middle-income countries. The aim of the present study was to assess HIV infection rates, evaluate HIV-1 genetic diversity, drug resistance, and to identify HIV transmission clusters in heavy drug users (DUs). For this purpose, DUs were recruited in the context of a Respondent-Driven Sampling (RDS) study in different Brazilian cities during 2009. Overall, 2,812 individuals were tested for HIV, and 168 (6%) of them were positive, of which 19 (11.3%) were classified as recent seroconverters, corresponding to an estimated incidence rate of 1.58%/year (95% CI 0.92–2.43%). Neighbor joining phylogenetic trees from env and pol regions and bootscan analyses were employed to subtype the virus from132 HIV-1-infected individuals. HIV-1 subtype B was prevalent in most of the cities under analysis, followed by BF recombinants (9%-35%). HIV-1 subtype C was the most prevalent in Curitiba (46%) and Itajaí (86%) and was also detected in Brasília (9%) and Campo Grande (20%). Pure HIV-1F infections were detected in Rio de Janeiro (9%), Recife (6%), Salvador (6%) and Brasília (9%). Clusters of HIV transmission were assessed by Maximum likelihood analyses and were cross-compared with the RDS network structure. Drug resistance mutations were verified in 12.2% of DUs. Our findings reinforce the importance of the permanent HIV-1 surveillance in distinct Brazilian cities due to viral resistance and increasing subtype heterogeneity all over Brazil, with relevant implications in terms of treatment monitoring, prophylaxis and vaccine development.

Anti-human immunodeficiency virus-1 antibody titers in injection drug users compared to sexually infected individuals

Sera from infected injection drug users (IDU) have shown to have antibodies against synthetic human immunodeficiency virus-1 (HIV-1) envelope peptides more frequently. In this study, reactivity of 48 IDU plasma were compared to 60 plasmas obtained from sexually infected individuals (S). The overall reactivity of plasma from IDU compared to S was higher, and the reactivity titers were much higher for IDU plasma than S. IDU plasma also showed a broader antibody response. The higher reactivity titers were observed mainly for the gp41 immunodominant epitope and V3 peptides corresponding to the consensus sequences of HIV-1 subtypes/variants prevalent in Brazil (B, F, C) indicating the specificity in the higher immune response of IDU.

Impact of HIV-1 Subtypes on AIDS Progression in a Brazilian Cohort.

Viral and host factors are known to play a role in the different patterns of AIDS progression. The cocirculation of HIV-1 subtypes B, F1, BBR, and BF1; the occasional detection of HIV-1 subtype D; and an increasing prevalence of subtype C and other recombinant forms have been described in Rio de Janeiro, Brazil. The aim of this study was to evaluate the potential association of HIV-1 subtypes circulating among HIV-1+ individuals in Rio de Janeiro with AIDS disease progression. For this purpose, 246 HIV-1 individuals under clinical and laboratory follow-up from 1986 to 2011 were classified according to their progression to AIDS in typical progressors (n = 133), rapid progressors (n = 95), and long-term nonprogressors (n = 18). The env-gp120 region was amplified and sequenced. Neighbor-joining phylogenetic inferences were performed in Mega 6 and bootscan analysis was performed in Simplot 3.5.1. The Kaplan-Meier method and Cox modeling were performed to determine the time until an AIDS-defining event based on the HIV-1 subtypes/variants. Similar AIDS progression rates were observed among individuals infected with HIV-1 subtype B and variant BBR. However, a direct association between more rapid AIDS progression and HIV-1 subtypes, D and BF1, was confirmed in the multivariate analysis, corroborating previous results. Our findings contribute to the investigation of the possible influence of HIV-1 subtypes in AIDS outcome.