Effects of Initiating Raltegravir-Based Versus Efavirenz-Based Antiretroviral Regimens During Pregnancy on Weight Changes and Perinatal Outcomes: NICHD P1081.

BACKGROUND: Integrase inhibitors have been associated with excess gestational weight gain that may lead to adverse pregnancy outcomes (APOs). This post hoc analysis of NICHD P1081 compared antepartum changes in weight and body mass index (BMI) in pregnant women initiating raltegravir- or efavirenz-based combined antiretroviral therapy (cART) and examined associations between rates of weight gain and APOs. SETTING: NICHD P1081 enrolled antiretroviral-naive pregnant women living with HIV in the second and third trimester in Brazil, Tanzania, South Africa, Thailand, Argentina, and the United States. METHODS: Two hundred eighty-one women enrolled between 20 and 31 gestational weeks were randomized to raltegravir- or efavirenz-based cART and followed for ≥4 weeks. A low rate of weight gain was defined as <0.18 kg/wk and high as >0.59 kg/wk. We compared weight gain and BMI increase between treatment arms using Kruskal-Wallis tests. Logistic regression was used to investigate the association between weight gain and APOs. RESULTS: Raltegravir-based cART was associated with significantly higher antepartum weight gain (median 0.36 kg/wk versus 0.29 kg/wk, P = 0.01) and BMI increase (median 0.14 kg/m 2 /wk versus 0.11 kg/m 2 /wk, P = 0.01) compared with efavirenz-based treatment. Women on raltegravir had less low weight gain (18% versus 36%) and more high weight gain (21% versus 12%) ( P = 0.001). Women with low weight gain were more likely than those with normal weight gain to have small for gestational age infants or a composite of APOs. CONCLUSIONS: A raltegravir-based antiretroviral regimen was associated with significantly higher antepartum rate of weight gain and BMI increase compared with efavirenz-based treatment in antiretroviral-naive pregnant women.

Association between circulating exhausted CD4+ T cells with poor meningococcal C conjugate vaccine antibody response in HIV-infected children and adolescents.

OBJECTIVES: To investigate the expression levels of surface markers of activation (CD38 and HLA-DR), inhibition (PD-1, TIGIT and CD57) and co-stimulation (CD28 and CD127) on CD4+ T cells of children/adolescents with vertical HIV infection (HI patients) and HIV-uninfected (HU) controls vaccinated with the meningococcal C conjugate vaccine (MCC). METHODS: HI patients (n=12), aged 8-17 years, were immunized with two MCC injections, while HU controls (n=9), aged 5.3-10.7 years, received a single MCC dose (as per national recommendation at the time of this study, a single MCC vaccine dose should be given for healthy children and youth aged 1-18 years). The HI patients were categorized according to the combined antiretroviral therapy (cART) treatment. Blood samples were obtained before vaccination, after priming, and after the administration of a booster dose of vaccine to determine the serum bactericidal antibody (SBA) titers and the expression levels of surface markers on CD4+ T cells by flow cytometry. The levels of serum cytokines, IL-4 and CXCL-13 were also measured using Luminex kits. RESULTS: The co-expression of the TIGIT-HLA-DR-CD38 molecules increased in the CD4+ T cells of HI patients/no-cART who also showed a lower frequency of CD127+CD28+ CD4+ T cells than HI patients/cART and HU group subjects. There were significant negative correlations between the frequency of exhausted CD4+ T cells and the SBA response. IL-4 levels were higher in HI patients/cART and positively correlated with SBA titers but negatively associated with the expression of exhaustion markers. Moreover, the CXCL-13 levels were positively correlated with the exhausted CD4+ T cells. CONCLUSION: The results of our study suggest that the co-expression of exhaustion markers and/or loss of co-stimulatory molecules influence the SBA response in HI patients.

Association between circulating exhausted CD4+ T cells with poor meningococcal C conjugate vaccine antibody response in HIV-infected children and adolescents

OBJECTIVES: To investigate the expression levels of surface markers of activation (CD38 and HLA-DR), inhibition (PD-1, TIGIT and CD57) and co-stimulation (CD28 and CD127) on CD4+ T cells of children/adolescents with vertical HIV infection (HI patients) and HIV-uninfected (HU) controls vaccinated with the meningococcal C conjugate vaccine (MCC). METHODS: HI patients (n=12), aged 8-17 years, were immunized with two MCC injections, while HU controls (n=9), aged 5.3-10.7 years, received a single MCC dose (as per national recommendation at the time of this study, a single MCC vaccine dose should be given for healthy children and youth aged 1-18 years). The HI patients were categorized according to the combined antiretroviral therapy (cART) treatment. Blood samples were obtained before vaccination, after priming, and after the administration of a booster dose of vaccine to determine the serum bactericidal antibody (SBA) titers and the expression levels of surface markers on CD4+ T cells by flow cytometry. The levels of serum cytokines, IL-4 and CXCL-13 were also measured using Luminex kits. RESULTS: The co-expression of the TIGIT-HLA-DR-CD38 molecules increased in the CD4+ T cells of HI patients/no-cART who also showed a lower frequency of CD127+CD28+ CD4+ T cells than HI patients/cART and HU group subjects. There were significant negative correlations between the frequency of exhausted CD4+ T cells and the SBA response. IL-4 levels were higher in HI patients/cART and positively correlated with SBA titers but negatively associated with the expression of exhaustion markers. Moreover, the CXCL-13 levels were positively correlated with the exhausted CD4+ T cells. CONCLUSION: The results of our study suggest that the co-expression of exhaustion markers and/or loss of co-stimulatory molecules influence the SBA response in HI patients.

Composite Analysis of the Virome and Bacteriome of HIV/HPV Co-Infected Women Reveals Proxies for Immunodeficiency.

The human cervical microbiome is complex, and its role in health and disease has just begun to be elucidated. In this study, 57 cervical swab samples from 19 HIV/HPV co-infected women were analyzed for both virome and bacteriome composition. Virome analysis focused on circular DNA viruses through rolling circle amplification followed by next-generation sequencing (NGS). Data were assigned to virus families and genera, and HPV types were identified. NGS data of bacterial 16S from a subset of 24 samples were assigned to operational taxonomic units and classified according to vaginal microbiome community state types (CSTs). Four viral families were found: Papillomaviridae, Anelloviridae, Genomoviridae, and Herpesviridae. Papillomavirus reads were more abundant in women with premalignant cervical lesions, which were also strongly associated with multiple (≥3) high-risk HPV infection. Anellovirus read abundance was negatively correlated with host CD4+ T-cell counts. The bacteriome revealed the presence of CST III and CST IV, and women with ≥1% frequency of genomovirus or herpesvirus reads displayed an increased risk of carrying CST IV. By characterizing the composition of the cervical circular DNA viruses and the bacteriome of HIV/HPV co-infected women, we identified putative interactions between these two microorganism communities and their associations with patients' clinical characteristics, notably immunodeficiency status.

Factors associated with the development of Congenital Zika Syndrome: a case-control study.

BACKGROUND: We aim to investigate possible maternal- and pregnancy-related factors associated with the development of Congenital Zika Syndrome (CZS) in children of mothers with probable gestational infection. METHODS: This case-control study, we recruited mother-infant pairs between May 2015 and October 2017 in a pediatric infectious disease clinic in Rio de Janeiro. Inclusion criteria required either that the mother reported Zika infection symptoms during pregnancy or that the infant presented with clinical or imaging features of the CZS. Exclusion criteria included detection of an alternative cause for the patient's presentation or negative polymerase chain reaction assays for Zika in all specimens tested within 12 days from the beginning of maternal symptoms. Infants with CZS (CDC definition) were selected as cases and infants without CZS, but with probable maternal Zika virus infection during pregnancy, were selected as controls. Maternal and pregnancy-related informations were collected and their relationship to the presence of congenital anomalies due to CZS was assessed by Fisher exact or Mann-Whitney test. RESULTS: Out of the 42 included neonates, 24 (57.1%) were diagnosed with CZS (cases). The mean maternal age at the birth was 21 years old. The early occurrence of maternal symptoms during pregnancy was the only variable associated with CZS (odds ratio = 0.87, 95% CI: 0.78-0.97). Case's mothers presented symptoms until the 25th week of gestational age (GA), while control's mothers presented until 36th weeks of GA. Income; illicit drug, alcohol, or tobacco use during pregnancy; other infections during pregnancy (including previous dengue infection) were not associated with CZS. CONCLUSIONS: Our study corroborates the hypothesis that Zika virus infection earlier in pregnancy is a risk factor to the occurrence of congenital anomalies in their fetuses.

Safety and immune response after two-dose meningococcal C conjugate immunization in HIV-infected children and adolescents in Rio de Janeiro, Brazil.

We aimed to evaluate immunogenicity and adverse events (AEs) after a booster dose of Meningococcal C conjugated (MCC) vaccine in HIV-infected children and adolescents, who had a previous low seroconversion rate after priming with MCC, at a reference HIV-care center in Rio de Janeiro. METHODS: 2-18 years old HIV-infected subjects with CD4+ T-lymphocyte cell (CD4) ≥15%, without active infection or antibiotic use, were enrolled to receive 2 doses of conjugated meningococcal C oligosaccharide-CRM197 12-18 months apart. All patients were evaluated before and 1-2 months after immunization for seroprotection [defined as human serum bactericidal activity (hSBA) titer ≥1:4]. AEs were assessed at 20 min, 3 and 7 days after each dose. Factors independently associated with seroprotection were studied. RESULTS: 156 subjects were enrolled and 137 received a booster MCC dose. 55% were female, and median age was 12 years. Eight-nine percent were receiving combined antiretroviral therapy (cART) at the booster visit (median duration of 7.7 years), 59.9% had undetectable viral load (VL) at baseline, and 56.2% at the booster visit. Seroprotection was achieved in 78.8% (108/137) subjects, with a significantly higher GMT than after the priming dose (p < 0.01). Mild AEs were experienced after a second MCC dose (38%). In logistic regression, undetectable viral load at entry [odds ratio (OR) = 7.1, 95% confidence interval (95%CI): 2.14-23.37], and probably higher CD4 percent at the booster immunization visit (OR): 1.1, 95%CI: 1.01-1.17 were associated with seroprotection after a booster dose of MCC. CONCLUSION: A booster dose of MCC was safe and induced high seroprotection rate even 12-18 months after priming. MCC should be administered after maximum virologic suppression has been achieved. These results support the recommendation of 2-dose of MCC for primary immunization in HIV-infected children and adolescents with restored immune function.

Antibody persistence following meningococcal C conjugate vaccination in children and adolescents infected with human immunodeficiency virus / Persistência de anticorpos seguida de vacina conjugada meningocócica C em crianças e adolescentes infectados por vírus da imunodeficiência humana

Abstract Objective: HIV-infected individuals (HIVI) are threatened by meningococcal infection and presented lower response to vaccines. Data are scarce on long-term persistence of human serum bactericidal antibody (hSBA) after a meningococcal C conjugate (MCC) vaccine in HIVI youth; the authors aimed to describe this persistence in HIVI. Methods: HIVI and HIV uninfected individuals (HIVU), aged 2-18 years, CD4 >15% were recruited. Seroprotection (hSBA ≥1:4) at baseline and at 12-18 months after immunization was evaluated and the association of the different factors with the long-term persistence was calculated using logistic regression. Results: A total of 145 HIVI, 50 HIVU were recruited and immunized, and their median age was 11 years (median age in HIVI group was 12 years, and 10 years in HIVU group, p-value = 0.02). 85 HIVI (44%) had undetectable viral load (UVL). Seroprotection rate was 27.2%: 24.1% in HIVI and 36% in HIVU 12-18 months after immunization (p = 0.14). Baseline immunity (odds ratio [OR] = 70.70, 95% CI: 65.2-766.6); UVL at entry (OR: 2.87, 95% CI: 0.96-8.62) and lower family income (OR: 0.09, 95% CI: 0.01-0.69) were associated with seroprotection among HIVI. Conclusion: Seroprotection at 12-18 months after single dose of MCC was low for both groups, and higher among individuals who presented baseline immunity. Among HIVI, vaccine should be administered after UVL is achieved.

Resumo Objetivo: As pessoas infectadas pelo HIV (HIVI) estão sujeitas a infecção meningocócica e apresentam menor resposta a vacinas. São escassos os dados a respeito da persistência de longo prazo do anticorpo bactericida no soro humano (hSBA) após vacina conjugada meningocócica C (MCC) em HIVI jovens e visamos a descrever essa persistência em HIVI. Métodos: Foram recrutadas pessoas HIVI e pessoas não infectadas por HIV (HIVU), entre 2 e 18 anos, CD4 > 15%. A seroproteção (hSBA ≥ 1:4) basal aos 12-18 meses após a imunização foi avaliada e a associação dos diferentes fatores com a persistência de longo prazo foi calculada com a regressão logística. Resultados: Foram recrutados 145 HIVI e 50 HIVU e imunizados e sua idade média foi determinada em 11 anos (12 no grupo HIVI e 10 no grupo HIVU, valor de p = 0,02); 85 HIVI (44%) apresentaram carga viral indetectável (CVI). A taxa de seroproteção foi 27,2%: 24,1% no grupo HIVI e 36% no grupo HIVU 12-18 meses após imunização (p = 0,14). A imunidade basal [razão de chance (RC) = 7070, IC: 65,2-7666]; CVI no momento da participação (RC: 2,87, IC de 95%: 0,96-8,62) e renda familiar mais baixa (RC: 0,09, IC de 95%: 0,01-0,69) foram associadas a seroproteção entre as pessoas HIVI. Conclusão: A seroproteção aos 12-18 meses após única dose de MCC mostrou-se baixa em ambos os grupos e mais elevada entre as pessoas que apresentaram imunidade basal. Entre as pessoas HIVI, as vacinas devem ser administradas após a CVI ser atingida.

A cross-reacting material CRM197 conjugate vaccine induces diphtheria toxin neutralizing antibody response in children and adolescents infected or not with HIV.

Anti-diphtheria antibody levels decrease with aging, and frequent booster vaccinations are required to maintain herd immunity. We analyzed the diphtheria toxin neutralizing antibody (DT-Nab) response induced by a conjugate vaccine (meningococcal C polysaccharide-CRM197) in HIV-vertically infected (HI) children and adolescents and healthy controls (HC) with matched age. We report the association of DT-Nab with the bactericidal antibodies to serogroup C meningococcus (MenC). Before vaccination, 21 HI patients (50%) had no protection against diphtheria (≤0.01IU/ml of antibody) and only 8 (19%) showed complete protection (≥0.1IU/ml). About half of the HC (56%) had complete protection before immunization and 6 subjects (12%) had no protection against diphtheria. After one and two vaccine injections, 96% of HC and 64% of HI vaccinees, respectively, showed full protection against diphtheria. These data indicate that CRM197 was able to induce primary and/or booster response in both groups of individuals.

Antibody persistence following meningococcal C conjugate vaccination in children and adolescents infected with human immunodeficiency virus.

OBJECTIVE: HIV-infected individuals (HIVI) are threatened by meningococcal infection and presented lower response to vaccines. Data are scarce on long-term persistence of human serum bactericidal antibody (hSBA) after a meningococcal C conjugate (MCC) vaccine in HIVI youth; the authors aimed to describe this persistence in HIVI. METHODS: HIVI and HIV uninfected individuals (HIVU), aged 2-18 years, CD4 >15% were recruited. Seroprotection (hSBA ≥1:4) at baseline and at 12-18 months after immunization was evaluated and the association of the different factors with the long-term persistence was calculated using logistic regression. RESULTS: A total of 145 HIVI, 50 HIVU were recruited and immunized, and their median age was 11 years (median age in HIVI group was 12 years, and 10 years in HIVU group, p-value=0.02). 85 HIVI (44%) had undetectable viral load (UVL). Seroprotection rate was 27.2%: 24.1% in HIVI and 36% in HIVU 12-18 months after immunization (p=0.14). Baseline immunity (odds ratio [OR]=70.70, 95% CI: 65.2-766.6); UVL at entry (OR: 2.87, 95% CI: 0.96-8.62) and lower family income (OR: 0.09, 95% CI: 0.01-0.69) were associated with seroprotection among HIVI. CONCLUSION: Seroprotection at 12-18 months after single dose of MCC was low for both groups, and higher among individuals who presented baseline immunity. Among HIVI, vaccine should be administered after UVL is achieved.

Association of serum bactericidal antibody and opsonic antibody levels after Neisseria meningitidis serogroup C conjugate vaccine in Brazilian children and adolescents infected or not infected with HIV.

Neisseria meningitidis serogroup C (MenC) is the main causative agent of meningitis in Brazil. HIV infection affects the quality of the immune system. HIV+ children have an increased risk of infection to encapsulated bacteria such as N. meningitidis. We evaluated the opsonic antibody (OPA) levels and its correlation with serum bactericidal antibody (SBA) levels induced by one and two doses of a MenC conjugate vaccine in children and adolescents HIV+ and HIV-exposed but uninfected children (HEU) group. Overall the data show the importance of two doses of vaccine for HIV+ individuals. About 79% and 58% of HIV+ patients showed SBA and OPA positive response after two doses of vaccine, respectively. For HEU group, 62% and 41% of patients showed SBA and OPA positive response after one dose of vaccine, respectively. A positive and significant association between SBA and OPA levels was seen after two doses of vaccine in HIV+ patients.

Bonafide, type-specific human papillomavirus persistence among HIV-positive pregnant women: predictive value for cytological abnormalities, a longitudinal cohort study.

This study investigated the rate of human papillomavirus (HPV) persistence, associated risk factors, and predictors of cytological alteration outcomes in a cohort of human immunodeficiency virus-infected pregnant women over an 18-month period. HPV was typed through L1 gene sequencing in cervical smears collected during gestation and at 12 months after delivery. Outcomes were defined as nonpersistence (clearance of the HPV in the 2nd sample), re-infection (detection of different types of HPV in the 2 samples), and type-specific HPV persistence (the same HPV type found in both samples). An unfavourable cytological outcome was considered when the second exam showed progression to squamous intraepithelial lesion or high squamous intraepithelial lesion. Ninety patients were studied. HPV DNA persistence occurred in 50% of the cases composed of type-specific persistence (30%) or re-infection (20%). A low CD4+T-cell count at entry was a risk factor for type-specific, re-infection, or HPV DNA persistence. The odds ratio (OR) was almost three times higher in the type-specific group when compared with the re-infection group (OR = 2.8; 95% confidence interval: 0.43-22.79). Our findings show that bonafide (type-specific) HPV persistence is a stronger predictor for the development of cytological abnormalities, highlighting the need for HPV typing as opposed to HPV DNA testing in the clinical setting.

Bonafide, type-specific human papillomavirus persistence among HIV-positive pregnant women: predictive value for cytological abnormalities, a longitudinal cohort study

This study investigated the rate of human papillomavirus (HPV) persistence, associated risk factors, and predictors of cytological alteration outcomes in a cohort of human immunodeficiency virus-infected pregnant women over an 18-month period. HPV was typed through L1 gene sequencing in cervical smears collected during gestation and at 12 months after delivery. Outcomes were defined as nonpersistence (clearance of the HPV in the 2nd sample), re-infection (detection of different types of HPV in the 2 samples), and type-specific HPV persistence (the same HPV type found in both samples). An unfavourable cytological outcome was considered when the second exam showed progression to squamous intraepithelial lesion or high squamous intraepithelial lesion. Ninety patients were studied. HPV DNA persistence occurred in 50% of the cases composed of type-specific persistence (30%) or re-infection (20%). A low CD4+T-cell count at entry was a risk factor for type-specific, re-infection, or HPV DNA persistence. The odds ratio (OR) was almost three times higher in the type-specific group when compared with the re-infection group (OR = 2.8; 95% confidence interval: 0.43-22.79). Our findings show that bonafide (type-specific) HPV persistence is a stronger predictor for the development of cytological abnormalities, highlighting the need for HPV typing as opposed to HPV DNA testing in the clinical setting.

Immunogenicity and safety of meningococcal C conjugate vaccine in children and adolescents infected and uninfected with HIV in Rio de Janeiro, Brazil.

BACKGROUND: We aimed to evaluate the Meningococcal (Neisseria meningitidis) C conjugated (MCC) vaccine seroconversion and adverse events (AEs) in HIV-infected and HIV-uninfected children and adolescents in Rio de Janeiro, Brazil. METHODS: HIV-infected or HIV-uninfected subjects, 2-18 years old, with CD4+ T-lymphocyte cell (CD4) percentage >15%, without active infection or antibiotic use, were enrolled. All patients were evaluated before and 1-2 months after immunization for seroconversion (defined as ≥4-fold titer increase in human serum bactericidal activity) and at 20 minutes, 3 and 7 days after immunization for AEs. Factors associated with seroconversion among HIV-infected group were studied. RESULTS: Two hundred four subjects were enrolled: 154 HIV-infected and 50 HIV-uninfected. Median age was 12 years, and 53% were female. Among the HIV-infected group, 82 (53%) had a history of at least 1 C clinical category of Centers for Diseases Control and Prevention event, and 134 (87%) were using combination antiretroviral therapy. The median nadir CD4 percentage was 13% (0-47%). Seventy-six (37.3%) experienced mild AEs. Seroconversion occurred in 46 of 154 (30%) in the HIV-infected group and in 38 of 50 (76%) in the uninfected group (P < 0.01). Factors associated with seroconversion in the HIV-infected group were as follows: never had a C clinical category event [odds ratio (OR) = 2.1, 95% confidence interval (CI): 1.0-4.4]; undetectable viral load at immunization (OR: 2.4, 95% CI: 1.1-5.2) and higher CD4 nadir/100 cells (OR: 1.1, 95% CI: 1.0-1.2). CONCLUSION: MCC vaccine should be administered to HIV-infected children and adolescents after maximum immunologic and virologic benefits have been achieved with combination antiretroviral therapy. Our data suggest that a single dose of MCC vaccine is insufficient for HIV-infected individuals 2-18 years of age.

Subsets of memory CD4+ T cell and bactericidal antibody response to Neisseria meningitidis serogroup C after immunization of HIV-infected children and adolescents.

Meningococcal disease is endemic in Brazil, with periodic outbreaks and case fatality rates reach as high as 18 to 20% of cases. Conjugate vaccines against meningococci are immunogenic in healthy children. However, we have previously shown a poor bactericidal antibody response to a Men C conjugate vaccine in Brazilian HIV-infected children and adolescents after a single vaccine administration. The goal of the present work was to investigate associations between bactericidal antibody response induced by MenC vaccine and the frequency and activation profile (expression of CD38, HLA-DR and CCR5 molecules) of total CD4+ memory T cell sub-populations in HIV-1-infected children and adolescents. Responders to vaccination against MenC had a predominance (about 44%) of CD4+ TINTERMEDIATE subset followed by TTRANSITIONAL memory subset (23 to 26%). Importantly, CD4+ TINT frequency was positively associated with bactericidal antibody response induced by vaccination. The positive correlation persisted despite the observation that the frequency TINT CD38+HLA-DR+ was higher in responders. In contrast, CD4+ TCENTRAL MEMORY (TCM) subset negatively correlated with bactericidal antibodies. In conclusion, these data indicate that less differentiated CD+ T cells, like TCM may be constantly differentiating into intermediate and later differentiated CD4+ T cell subsets. These include CD4 TINT subset which showed a positive association with bactericidal antibodies.

Prevalence of lipodystrophy and risk factors for dyslipidemia in HIV-infected children in Brazil

The aim of present study was to describe the frequency of lipodystrophy syndrome associated with HIV (LSHIV) and factors associated with dyslipidemia in Brazilian HIV infected children. HIV infected children on antiretroviral treatment were evaluated (nutritional assessment, physical examination, and laboratory tests) in this cross-sectional study. Univariate analysis was performed using Mann-Whitney test or Fisher's exact test followed by logistic regression analysis. Presence of dyslipidemia (fasting cholesterol >200 mg/dl or triglycerides >130 mg/dl) was the dependent variable. 90 children were enrolled. The mean age was 10.6 years (3-16 years), and 52 (58%) were female. LSHIV was detected in 46 children (51%). Factors independently associated with dyslipidemia were: low intake of vegetables/fruits (OR = 3.47, 95%CI = 1.04-11.55), current use of lopinavir/ritonavir (OR = 2.91, 95%CI = 1.11-7.67). In conclusion, LSHIV was frequently observed; inadequate dietary intake of sugars and fats, as well as current use of lopinavir/ritonavir was associated with dyslipidemia.

Prevalence of lipodystrophy and risk factors for dyslipidemia in HIV-infected children in Brazil.

The aim of present study was to describe the frequency of lipodystrophy syndrome associated with HIV (LSHIV) and factors associated with dyslipidemia in Brazilian HIV infected children. HIV infected children on antiretroviral treatment were evaluated (nutritional assessment, physical examination, and laboratory tests) in this cross-sectional study. Univariate analysis was performed using Mann-Whitney test or Fisher's exact test followed by logistic regression analysis. Presence of dyslipidemia (fasting cholesterol >200mg/dl or triglycerides >130mg/dl) was the dependent variable. 90 children were enrolled. The mean age was 10.6 years (3-16 years), and 52 (58%) were female. LSHIV was detected in 46 children (51%). Factors independently associated with dyslipidemia were: low intake of vegetables/fruits (OR=3.47, 95%CI=1.04-11.55), current use of lopinavir/ritonavir (OR=2.91, 95%CI=1.11-7.67). In conclusion, LSHIV was frequently observed; inadequate dietary intake of sugars and fats, as well as current use of lopinavir/ritonavir was associated with dyslipidemia.

Short communication: kidney dysfunction among HIV-infected children in Latin America and the Caribbean.

Renal toxicity is a concern in HIV-infected children receiving antiretrovirals. However, the prevalence [1.7%; 95% confidence interval (CI): 1.0-2.6%] and incidence of kidney dysfunction (0.17 cases/100 person-years; 95% CI: 0.04-0.30) were rare in this multicenter cohort study of 1,032 perinatally HIV-infected Latin American and Caribbean children followed from 2002 to 2011.

Hypertension, preeclampsia and eclampsia among HIV-infected pregnant women from Latin America and Caribbean countries.

OBJECTIVES: To evaluate the incidence of and risk factors for hypertensive disorders in a cohort of HIV-infected pregnant women. METHODS: Hypertensive disorders (HD) including preeclampsia/eclampsia (PE/E) and pregnancy induced hypertension, and risk factors were evaluated in a cohort of HIV-infected pregnant women from Latin America and the Caribbean enrolled between 2002 and 2009. Only pregnant women enrolled for the first time in the study and delivered at ≥20 weeks gestation were analyzed. RESULTS: HD were diagnosed in 73 (4.8%, 95% CI: 3.8%-6.0%) of 1513 patients; 35 (47.9%) had PE/E. HD was significantly increased among women with a gestational age-adjusted body mass index (gBMI) ≥25 kg/m(2) (OR = 3.1; 95% CI: 1.9-5.0), hemoglobin (Hg) ≥11 g/dL at delivery (OR = 2.1; 95% CI: 1.2-3.6) and age ≥35 years (OR = 1.8; 95% CI: 1.1-3.2). PE/E was increased among women with a gBMI ≥25 kg/m(2) (OR = 3.0; 95% CI: 1.5-6.0) and Hg ≥11 g/dL at delivery (OR = 2.8; 95% CI: 1.2-6.5). A previous history of PE/E increased the risk of PE/E 6.7 fold (95% CI: 1.8-25.5). HAART before conception was associated with PE/E (OR = 2.3; 95% CI: 1.1-4.9). CONCLUSIONS: HIV-infected women, with a previous history of PE/E, a gBMI ≥25 kg/m(2), Hg at delivery ≥11 g/dL and in use of HAART before conception are at an increased risk of developing PE/E during pregnancy.

CD4+ T-cell activation impairs serogroup C Neisseria meningitis vaccine response in HIV-infected children.

OBJECTIVE: To investigate the influence of CD4 T-cell activation and regulatory populations in HIV-infected children antibody response to vaccination with a conjugate C polysaccharide vaccine. DESIGN: CD4 T-cell activation was evaluated by expression of CD38, HLA-DR and CCR5 molecules. Regulatory CD4 T cells (TReg) were characterized as FoxP3CD127CD25 and inducer T cells (TInd) as CD4FoxP3CD25CD39. METHODS: All patients (n = 36) were HIV-vertically infected, aged 2-17 years-old and were vaccinated with one vaccine injection. Blood samples were obtained before and after immunization to determine bactericidal antibody titers (SBA), CD4 T-cell activation and frequency of TReg and TInd subsets (multiparametric flow cytometry). RESULTS: Children not-responding (n = 18) to MenC vaccine expressed higher frequency of activated CD4 T cells (HLA-DRCD38CCR5) than responders (n = 18), both before and after vaccination (P < 0.05). A significant higher frequency of TReg was detected in responders compared with nonresponders (P = 0.0001). We also detected an inverse correlation between CD4DRCD38CCR5 (P = 0.01) or CD4DRCD38 (P = 0.02) T cells and TReg cell frequency after vaccination. CD4 T-cell activation negatively correlated (P = 0.006) with postvaccination SBA titers but a positive correlation (P = 0.0001) was detected between TReg cells and SBA. TReg and TInd subsets were inversely correlated (P = 0.04). CONCLUSION: Our findings suggest that higher CD4 T-cell activation leads to poor vaccine response in children living with HIV, which may be associated with a TReg/TInd disequilibrium.