An in-depth analysis of the HIV-1/AIDS dynamics by comprehensive mathematical modeling

This work presents major results from a novel dynamic model intended to deterministically represent the complex relation between HIV-1 and the human immune system. The novel structure of the model extends previous work by representing different host anatomic compartments under a more in-depth cellular and molecular immunological phenomenology. Recently identified mechanisms related to HIV-1 infection as well as other well known relevant mechanisms typically ignored in mathematical models of HIV-1 pathogenesis and immunology, such as cell-cell transmission, are also addressed. (C) 2011 Elsevier Ltd. All rights reserved.

Body changes: antiretroviral therapy and lipodystrophy syndrome in people living with HIV/aids

Objective: to identify the different types of morphological alterations from lipodystrophy syndrome (LS) in outpatients and relate them to the therapeutic regimen used. Method: a cross-sectional study which recruited 60 patients with HIV and LS and 79 without LS, who consented to interview and data collection from their medical notes. Results: the region most affected by lipoatrophy was the face; by lipohypertrophy, the abdomen, and by the mixed form, the alterations to the abdomen, face, and upper and lower limbs. Conclusion: among the therapeutic regimens, that comprised of zidovudine, lamivudine and efavirenz seemed to protect against LS. Nursing can act in the early identification of the changes, as well as providing guidance and support for patients affected by the changes in their body image.

Frequency of subtype B and F1 dual infection in HIV-1 positive, Brazilian men who have sex with men

Background: Because various HIV vaccination studies are in progress, it is important to understand how often inter- and intra-subtype co/superinfection occurs in different HIV-infected high-risk groups. This knowledge would aid in the development of future prevention programs. In this cross-sectional study, we report the frequency of subtype B and F1 co-infection in a clinical group of 41 recently HIV-1 infected men who have sex with men (MSM) in Sao Paulo, Brazil. Methodology: Proviral HIV-1 DNA was isolated from subject's peripheral blood polymorphonuclear leukocytes that were obtained at the time of enrollment. Each subject was known to be infected with a subtype B virus as determined in a previous study. A small fragment of the integrase gene (nucleotide 4255-4478 of HXB2) was amplified by nested polymerase chain reaction (PCR) using subclade F1 specific primers. The PCR results were further confirmed by phylogenetic analysis. Viral load (VL) data were extrapolated from the medical records of each patient. Results: For the 41 samples from MSM who were recently infected with subtype B virus, it was possible to detect subclade F1 proviral DNA in five patients, which represents a co-infection rate of 12.2%. In subjects with dual infection, the median VL was 5.3 x 10(4) copies/ML, whereas in MSM that were infected with only subtype B virus the median VL was 3.8 x 10(4) copies/ML (p > 0.8). Conclusions: This study indicated that subtype B and F1 co-infection occurs frequently within the HIV-positive MSM population as suggested by large number of BF1 recombinant viruses reported in Brazil. This finding will help us track the epidemic and provide support for the development of immunization strategies against the HIV.

Broad and Cross-Clade CD4(+) T-Cell Responses Elicited by a DNA Vaccine Encoding Highly Conserved and Promiscuous HIV-1 M-Group Consensus Peptides

T-cell based vaccine approaches have emerged to counteract HIV-1/AIDS. Broad, polyfunctional and cytotoxic CD4(+) T-cell responses have been associated with control of HIV-1 replication, which supports the inclusion of CD4(+) T-cell epitopes in vaccines. A successful HIV-1 vaccine should also be designed to overcome viral genetic diversity and be able to confer immunity in a high proportion of immunized individuals from a diverse HLA-bearing population. In this study, we rationally designed a multiepitopic DNA vaccine in order to elicit broad and cross-clade CD4(+) T-cell responses against highly conserved and promiscuous peptides from the HIV-1 M-group consensus sequence. We identified 27 conserved, multiple HLA-DR-binding peptides in the HIV-1 M-group consensus sequences of Gag, Pol, Nef, Vif, Vpr, Rev and Vpu using the TEPITOPE algorithm. The peptides bound in vitro to an average of 12 out of the 17 tested HLA-DR molecules and also to several molecules such as HLA-DP, -DQ and murine IA(b) and IA(d). Sixteen out of the 27 peptides were recognized by PBMC from patients infected with different HIV-1 variants and 72% of such patients recognized at least 1 peptide. Immunization with a DNA vaccine (HIVBr27) encoding the identified peptides elicited IFN-gamma secretion against 11 out of the 27 peptides in BALB/c mice; CD4(+) and CD8(+) T-cell proliferation was observed against 8 and 6 peptides, respectively. HIVBr27 immunization elicited cross-clade T-cell responses against several HIV-1 peptide variants. Polyfunctional CD4(+) and CD8(+) T cells, able to simultaneously proliferate and produce IFN-gamma and TNF-alpha, were also observed. This vaccine concept may cope with HIV-1 genetic diversity as well as provide increased population coverage, which are desirable features for an efficacious strategy against HIV-1/AIDS.

Expansion of a subset of CD14(high)CD16(neg)CCR2(low/neg) monocytes functionally similar to myeloid-derived suppressor cells during SIV and HIV infection

Monocytes have been categorized in three main subpopulations based on CD14 and CD16 surface expression. Classical monocytes express the CD14(++)CD16(-) CCR2(+) phenotype and migrate to inflammatory sites by quickly responding to CCL2 signaling. Here, we identified and characterized the expansion of a novel monocyte subset during HIV and SIV infection, which were undistinguishable from classical monocytes, based on CD14 and CD16 expression, but expressed significantly lower surface CCR2. Transcriptome analysis of sorted cells demonstrated that the CCR2(low/neg) cells are a distinct subpopulation and express lower levels of inflammatory cytokines and activation markers than their CCR2(high) counterparts. They exhibited impaired phagocytosis and greatly diminished chemotaxis in response to CCL2 and CCL7. In addition, these monocytes are refractory to SIV infection and suppress CD8(+) T cell proliferation in vitro. These cells express higher levels of STAT3 and NOS2, suggesting a phenotype similar to monocytic myeloid-derived cells, which suppress expansion of CD8(+) T cells in vivo. They may reflect an antiproliferative response against the extreme immune activation observed during HIV and SIV infections. In addition, they may suppress antiviral responses and thus, have a role in AIDS pathogenesis. Antiretroviral therapy in infected macaque and human subjects caused this population to decline, suggesting that this atypical phenotype is linked to viral replication. J. Leukoc. Biol. 91: 803-816; 2012.

The impact of late diagnosis on the survival of patients following their first AIDS-related hospitalization in Belo Horizonte, Brazil

The purpose of this study is to estimate the survival probability of patients following their first admission for the treatment of AIDS to an infectious disease reference hospital in Belo Horizonte, Brazil, during 2005. Study subjects were monitored during a 12-month period to identify factors associated with survival probability. Late diagnosis was recorded among many of the 250 study subjects: almost half (44.8%) were diagnosed less than 30 days prior to or during their hospitalization. A high mortality rate was also detected: 39.6% of the subjects died during the 12 months of monitoring. The cumulative survival probability of the cohort group was estimated at 68.0% after 3 months and at 61.2% after 12 months. However, certain patient subgroups analyzed had even lower cumulative survival probabilities after 12 months of monitoring: if diagnosed during hospitalization, it was estimated at only 48.0% and those with no record of antiretroviral treatment had a 48.5% cumulative survival probability. Patients with severe anemia had the lowest survival probability, similar among the two lymphocyte count groups (<1000 mm(3) and >= 1000 mm(3)), the former with a 45.5% survival probability and the latter with a 46.7% one. The proportional death risk was 2.5-fold higher for men residing in other area than the capital city of the State of Minas Gerais and greater metropolitan region when compared with women residing there. The findings of this study highlight the importance of early diagnosis for predicting patient survival and reinforce the necessity off acilitating HIV diagnosis.

Prevalence and vulnerability of homeless people to HIV infection in Sao Paulo, Brazil

OBJECTIVE: To assess the prevalence and vulnerability of homeless people to HIV infection. METHODS: Cross-sectional study conducted with a non-probabilistic sample of 1,405 homeless users of shelters in the city of Sao Paulo, southeastern Brazil, from 2006 to 2007. They were all tested for HIV and a structured questionnaire was applied. Their vulnerability to HIV was determined by the frequency of condom use: those who reported using condoms only occasionally or never were considered the most vulnerable. Multinomial and logistic regression models were used to estimate effect measures and 95% confidence intervals. RESULTS: There was a predominance of males (85.6%), with a mean age of 40.9 years, 72.0% had complete elementary schooling, and 71.5% were non-white. Of all respondents, 15.7% reported being homosexual or bisexual and 62,0% reported having casual sex. The mean number of sexual partners in the last 12 months was 5.4. More than half (55.7%) of the respondents reported lifetime drug use, while 25.7% reported frequent use. Sexually-transmitted disease was reported by 39.6% of the homeless and 38.3% reported always using condoms. The prevalence of HIV infection was 4.9% (17.4% also tested positive for syphilis) and about half of the respondents (55.4%) had access to prevention programs. Higher HIV prevalence was associated with younger age (18-29 years, OR = 4.0 [95% CI 1.54; 10.46]); past history of sexually-transmitted disease (OR = 3.3 [95% CI 1.87; 5.73]); homosexual sex (OR = 3.0 [95% CI 1.28; 6.92]); and syphilis (OR = 2.4 [95% CI 1.13; 4.93]). Increased vulnerability to HIV infection was associated with being female; young; homosexual sex; having few partners or a steady partner; drug and alcohol use; not having access to prevention programs and social support. CONCLUSIONS: The HIV epidemic has a major impact on homeless people reflecting a cycle of exclusion, social vulnerability, and limited access to prevention.

Faster HIV-1 Disease Progression among Brazilian Individuals Recently Infected with CXCR4-Utilizing Strains

Introduction: Primary HIV infection is usually caused by R5 viruses, and there is an association between the emergence of CCXR4-utilizing strains and faster disease progression. We characterized HIV-1 from a cohort of recently infected individuals in Brazil, predicted the virus's co-receptor use based on the env genotype and attempted to correlate virus profiles with disease progression. Methods: A total of 72 recently infected HIV patients were recruited based on the Serologic Testing Algorithm for Recent HIV Seroconversion and were followed every three to four months for up to 78 weeks. The HIV-1 V3 region was characterized by sequencing nine to twelve weeks after enrollment. Disease progression was characterized by CD4+ T-cell count decline to levels consistently below 350 cells/mu L. Results: Twelve out of 72 individuals (17%) were predicted to harbor CXCR4-utilizing strains; a baseline CD4,350 was more frequent among these individuals (p = 0.03). Fifty-seven individuals that were predicted to have CCR5-utilizing viruses and 10 individuals having CXCR4-utilizing strains presented with baseline CD4.350; after 78 weeks, 33 individuals with CCR5 strains and one individual with CXCR4 strains had CD4.350 (p = 0.001). There was no association between CD4 decline and demographic characteristics or HIV-1 subtype. Conclusions: Our findings confirm the presence of strains with higher in vitro pathogenicity during early HIV infection, suggesting that even among recently infected individuals, rapid progression may be a consequence of the early emergence of CXCR4-utilizing strains. Characterizing the HIV-1 V3 region by sequencing may be useful in predicting disease progression and guiding treatment initiation decisions.

Human Endogenous Retrovirus K(HML-2) Gag and Env specific T-cell responses are not detected in HTLV-I-infected subjects using standard peptide screening methods

Abstract Background An estimated 10–20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial. Results Here, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets. Conclusions Thus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology.

TUBERCULOSIS AMONG HIV-1-INFECTED SUBJECTS IN A TERTIARY OUT-PATIENT SERVICE IN SÃO PAULO CITY, BRAZIL

TB is currently considered to be the most important infectious disease among HIV-1-infected subjects in developing countries, such as Brazil. A retrospective analysis of TB cases was performed, occurring from January 1995 to December 2010 in our cohort of 599 HIV positive patients. The primary outcome was the occurrence of active TB. Forty-one TB cases were diagnosed over this period of 16 years, among 599 HIV positive patients in an open cohort setting in the city of Sao Paulo, Brazil. All-time lowest mean CD4 T cell count at the time of TB diagnosis was 146 and 186 cells/mm3, respectively. The mean HIV viral load was 5.19 log10 copies/mL, and 59% of the patients were on HAART. TB incidence was 1.47 per 100 person-years, for a total follow-up time of 2775 person-years. The probability of surviving up to 10 years after diagnosis was 75% for TB patients as opposed to 96% for patients with other, non-TB opportunistic diseases (p = 0.03). TB can be considered a public health problem among people living with HIV in Brazil despite of the widespread use of antiretrovirals for the treatment of HIV infection/AIDS.

Assessment of tuberculosis treatment accessibility for patients co-infected or not with the human immunodeficiency virus

This study aimed to evaluate accessibility to treatment for people with TB co-infected or not with HIV. This cross-sectional study addressed issues regarding accessibility to treatment in a city in the interior of Sao Paulo state, Brazil. The instrument Primary Care Assessment Tool was utilized with 95 people. To evaluate access to treatment, Student's t test was used. The mean scores of variables were analyzed separately and compared between two groups (people with TB co-infected with HIV and people with TB not co-infected with HIV). Mean scores showed that HIV co-infected people presented greater difficulties in gaining access than those not co-infected. Professionals visited co-infected people more often when compared to those not co-infected; the co-infected people almost never accessed treatment for their disease in the Health Unit nearest their home. There is, therefore, the need for greater integration and communication between the programs for treatment of Tuberculosis and STD/AIDS.

Number of recent sexual partners among blood donors in Brazil: associations with donor demographics, donation characteristics, and infectious disease markers

BACKGROUND: Brazilian blood centers ask candidate blood donors about the number of sexual partners in the past 12 months. Candidates who report a number over the limit are deferred. We studied the implications of this practice on blood safety. STUDY DESIGN AND METHODS: We analyzed demographic characteristics, number of heterosexual partners, and disease marker rates among 689,868 donations from three Brazilian centers between July 2007 and December 2009. Donors were grouped based on maximum number of partners allowed in the past 12 months for each center. Chi-square and logistic regression analysis were conducted to examine associations between demographic characteristics, number of sex partners, and individual and overall positive markers rates for human immunodeficiency virus (HIV), human T-lymphotropic virus Types 1 and 2, hepatitis B virus, hepatitis C virus, and syphilis. RESULTS: First-time, younger, and more educated donors were associated with a higher number of recent sexual partners, as was male sex in Sao Paulo and Recife (p < 0.001). Serologic markers for HIV and syphilis and overall were associated with multiple partners in Sao Paulo and Recife (p < 0.001), but not in Belo Horizonte (p = 0.05, p = 0.94, and p = 0.75, respectively). In logistic regression analysis, number of recent sexual partners was associated with positive serologic markers (adjusted odds ratio [AOR], 1.2-1.5), especially HIV (AOR, 1.9-4.4). CONCLUSIONS: Number of recent heterosexual partners was associated with HIV positivity and overall rates of serologic markers of sexually transmitted infections. The association was not consistent across centers, making it difficult to define the best cutoff value. These findings suggest the use of recent heterosexual contacts as a potentially important deferral criterion to improve blood safety in Brazil.

Quality of sleep and quality of life in adolescents infected with human immunodeficiency virus

Objectives: To assess sleep characteristics of adolescents infected by HIV, and to ascertain whether psychosocial aspects are associated to the quality of sleep. Methods: A cross-sectional study assessing 102 HIV-infected adolescents of both genders, aged between 10 and 20 years-old and 120 Controls. Data collection was performed by applying the Sleep Disturbance Scale for Children, the Epworth Sleepiness Scale, and the Pediatric Quality of Life Inventory. Results: A sleep disturbance prevalence of 77.4% was found in patients, and a 75% prevalence in controls, and there was correlation between quality of sleep and of life. HIV-infected adolescents scored higher for sleep breathing disorders and had higher prevalence of excessive daytime sleepiness. Conclusions: HIV-infected adolescents had similar quality of sleep compared to healthy adolescents. This may be explained by the steady improvements in daily living as a result of successful anti-retroviral therapy, and by the vulnerability that affects Brazilian adolescents living in major urban centers.

Quality of life aspects of patients with HIV/tuberculosis co-infection

AIM: To investigate the quality of life of patients with HIV and tuberculosis co-infection and grasping the changes imposed in order to live with both transmissible diseases simultaneously. METHODS: Qualitative-quantitative research, undertaken at a specialized outpatient clinic in Fortaleza, Brazil, between 2009 and 2010, involving 34 co-infected patients. For data collection, a quality of life scale called HAT-QoL was used, which consists of 42 items, as well as open questions to perceive the changes the disease causes. RESULTS: Most participants suffered from pulmonary tuberculosis, were male and their education level was low. Quality of life was impaired in those domains related to economic, sexual and secrecy issues. It was also evidenced that the co-infection imposes changes in daily life that underline and further harm quality of life. CONCLUSION: Experiencing co-infection, despite appropriate treatment, causes changes in the patients' lives, whose repercussions can be mitigated through health-promoting interventions.

Factors associated with failure of clinical screening among blood donors who have altered serological results in the Centro Regional de Hemoterapia de Ribeirão Preto

OBJECTIVE: This study aimed to investigate the frequency of positive results for hepatitis B and C, HIV and syphilis in blood donations at the Centro Regional de Hemoterapia de Ribeirão Preto, to describe donors with positive results according to some demographic and socioeconomic variables, to identify risk factors associated to these donors and the reasons that they were not detected during clinical screening. METHODS: A descriptive study was performed between July 1st 2005 and July 31st 2006 by interviewing 106 donors after medical consultations where they were informed of positive results for hepatitis B, hepatitis C, HIV or syphilis. RESULTS: There was a predominance of first-time donors, males, under 50-year olds, married individuals, from Ribeirão Preto, with elementary education, low economic status and of people who donated at the request of friends or relatives. Hepatitis C was the most frequently detected infection (56.6%), followed by hepatitis B (20.7%), HIV (12.3%) and syphilis(10.4%). About 40% of donors had omitted risk factors for different reasons: because they trusted the results of serological tests, did not feel comfortable about talking of risk factors or did not consider them relevant. Other justifications were the duration of the interview, the interviewer was unskilled, embarrassment and doubts about confidentiality. CONCLUSION: The results indicate the need for changes in the approach to clinical screening and a review of methods to attract and guide potential donors.