Patterns of Antiretroviral Therapy Use and Immunologic Profiles at Enrollment in the REPRIEVE Trial.

BACKGROUND: Patterns of antiretroviral therapy (ART) use and immunologic correlates vary globally, and contemporary trends are not well described. METHODS: The REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV) enrolled persons with human immunodeficiency virus (HIV) who were aged 40-75 years, receiving ART, and had low-to-moderate cardiovascular disease risk. ART use was summarized within Global Burden of Disease (GBD) super-regions, with adjusted linear and logistic regression analyses examining associations with immune parameters and key demographics. RESULTS: A total of 7770 participants were enrolled, with a median age of 50 years (interquartile range, 45-55 years); 31% were female, 43% were black or African American, 15% were Asian, 56% had a body mass index >25 (calculated as weight in kilograms divided by height in meters squared), and 49% were current or former smokers. The median CD4 T-cell count was 620/µL (interquartile range, 447-826/ µ L), and the median duration of prior ART use, 9.5 years (5.3-14.8) years. The most common ART regimens were nucleoside/nucleotide reverse-transcriptase inhibitor (NRTI) plus nonnucleoside reverse-transcriptase inhibitor (43%), NRTI plus integrase strand transfer inhibitor (25%), and NRTI plus protease inhibitor (19%). Entry ART varied by GBD region, with shifts during the trial enrollment period. In adjusted analyses, entry CD4 cell count and CD4/CD8 ratio were associated with GBD region, sex, entry regimen, duration of ART, and nadir CD4 cell count; CD4 and CD8 cell counts were also associated with body mass index and smoking status. CONCLUSIONS: There were substantial variations in ART use by geographic region and over time, likely reflecting the local availability of specific medications, changes in treatment guidelines and provider/patient preferences. The analyses of CD4 cell counts and CD4/CD8 ratios may provide valuable insights regarding immune correlates and outcomes in people living with HIV. CLINICAL TRIALS REGISTRATION: NCT02344290.

HIV testing of male partners of pregnant women in Porto Alegre, Brazil: a potential strategy for reduction of HIV seroconversion during pregnancy.

Pregnant women have a significantly higher risk of HIV acquisition during gestation than their non-pregnant counterparts due to behavioral and biological factors. Acute seroconversion during gestation results in increased HIV mother-to-child transmission rates and has been identified as a major public health challenge. In order to address potential HIV seroconversion in our pregnant patients, we conducted a prospective cohort study to evaluate the acceptability of offering HIV testing to sexual partners of HIV-negative pregnant women receiving antenatal care at two hospitals in Porto Alegre, Brazil. Over a 14-month study period, HIV-negative pregnant women at two hospital-based clinic sites were encouraged to bring their stable sexual partner for HIV voluntary counseling and testing during prenatal care. Women were re-interviewed following delivery to measure success of the intervention. Of the 1223 HIV-negative pregnant women enrolled in the study, 663 (54%) of their male sexual partners received HIV testing during antenatal care and 4 (0.6%) were diagnosed with HIV infection. A total of 645 women were interviewed at the time of delivery, with 620 (97%) confirming that HIV testing was suggested to their partner. The most common reason provided by women as to why partners did not come for testing was work (69%) and lack of perceived risk (14%). Independent predictors of successful partner testing included being white (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.18-2.12), married (OR 1.78, 95% CI 1.08-2.94), having an older age of sexual debut (OR 0.94, 95% CI 0.9-0.98), and being recruited at Hospital Conceiçao (OR 2.1, 95% CI 1.52-2.88). We conclude that HIV partner testing during prenatal care is acceptable, rendering this intervention attractive to public health programs targeting prevention of sexually transmitted infections.

Cesarean delivery and risk of HIV vertical transmission in Southern Brazil, 2008-2018.

BACKGROUND: Childbirth via cesarean delivery can prevent intrapartum vertical transmission for women who are not virally suppressed at the time of delivery. Few studies have compared cesarean delivery trends between women living with HIV and women without HIV and have examined the role of cesarean delivery in the prevention of vertical transmission in the era of potent combination antiretroviral therapy. OBJECTIVE: We hypothesized that the cesarean delivery rate is high in women living with HIV compared with women without HIV and that cesarean delivery usage decreases over time among women living with HIV with advances in combined antiretroviral therapy in a country with a high national cesarean delivery rate. This study aimed (1) to evaluate cesarean delivery trends in women with and without HIV and (2) to examine its role in preventing vertical transmission among women living with HIV in a setting of free, universal combined antiretroviral therapy coverage in a retrospective cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of maternal HIV in Brazil. STUDY DESIGN: Data from maternal-infant pairs from January 1, 2008, to December 31, 2018, were extracted. Cesarean delivery rates were compared using the Pearson chi-square test. Cesarean delivery predictors were evaluated by multivariate log-linear Poisson regression using a generalized estimating equations approach. HIV viral suppression was defined as a viral load of <1000 copies/ml at delivery. HIV vertical transmission was determined following national guidelines. RESULTS: Over 11 years, 48,688 pregnancies occurred in 40,375 women; HIV seroprevalence was 2.7%; 18,886 cesarean deliveries (38.8%) were performed; 47.7% of women living with HIV and 38.6% of women without HIV underwent cesarean delivery (P<.001). Although HIV was associated with cesarean delivery (adjusted relative risk, 1.17 [95% confidence interval, 1.05-1.29]), women living with HIV with vertical transmission achieved similar cesarean delivery rates (36.7%) as women without HIV (39.8%) in 2018. Cesarean delivery in women living with HIV with an unknown viral load at delivery (42.6%) did not increase over time. HIV vertical transmission rate was 2.2%, the highest in women living with HIV with an unknown viral load (8.4%) vs women living with HIV without vertical transmission (4.1%) and women living with HIV with vertical transmission (0.5%) (P<.001). CONCLUSION: In the HIV epicenter of Brazil, women living with HIV with vertical transmission had fewer surgical deliveries, likely because of the use of potent combination antiretroviral therapy. Nearly half of the women living with HIV with an unknown viral load did not undergo cesarean delivery, a potential missed opportunity for the prevention of HIV vertical transmission.

Risk-taking behavior for HIV acquisition during pregnancy in Porto Alegre, Brazil.

Recent studies suggest that acquisition of HIV-1 infection during pregnancy and breastfeeding is associated with a high risk of HIV mother-to-child transmission. This study evaluates risk factors associated with HIV acquisition during pregnancy in women delivering at a large metropolitan medical facility located in the south of Brazil. From February to August 2009, our group conducted a cross-sectional study assessing women's risk for HIV acquisition by administering an oral survey to peripartum women. Of 2465 participants, 42% (n = 1046) knew that partner had been tested for HIV. During pregnancy, 82% (n = 2022) of participants never used condoms; yet 97% (n = 2399) practiced vaginal sex. Multivariate logistic regression analysis showed that patients with more years of education, in a relationship for more than 1 year, and who knew their own HIV status were more likely to know their partners' HIV status (P < 0.05). Those who were in relationship for more than 1 year and were married/living together were more likely to be comfortable discussing HIV testing with partners (P < 0.05). In conclusion, women in Brazil are at risk of HIV-infection during pregnancy as they remain sexually active, often do not know their sexual partner's HIV status, and have minimal condom use.

Patterns of pregnancy loss among women living with and without HIV in Brazil, 2008-2018.

BACKGROUND: Pregnancy loss is poorly understood, but infection may be a risk factor. Few studies have evaluated pregnancy loss among women living with HIV in the era of potent combination antiretroviral therapy. OBJECTIVE: We hypothesize that maternal HIV and syphilis infection lead to increased risk of pregnancy loss, including both miscarriage and stillbirth. This study aimed to assess trends and possible predictors of spontaneous miscarriage and stillbirth among women living with HIV in a cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of HIV in Brazil. STUDY DESIGN: Data from hospital records for women delivering from January 1, 2008 to December 31, 2018 were reviewed. Rates of stillbirth, miscarriage, and any pregnancy loss were compared using the Pearson chi-square test. Predictors of pregnancy loss were evaluated by robust univariate log-linear Poisson regression using a generalized estimating equations approach. RESULTS: A total of 55,844 pregnancies were included in the analysis, with 54,308 pregnancies from 43,502 women without HIV and 1536 pregnancies from 1186 women living with HIV (seroprevalence of maternal HIV: 2.7%). Overall, 1130 stillbirths (2.0%) and 6558 miscarriages (11.7%) occurred. Any pregnancy loss was similar in both groups (13.8% in women without and 14.1% in women with HIV; P=.733). Stillbirth was higher among women living with HIV (3.4%) than among women without HIV (2.0%; P<.001), but there was no difference in overall miscarriage rates (10.7% in women with vs. 11.8% in women without HIV; P=.188). Women living with HIV had higher miscarriage rates between 12 and 20 weeks than women without HIV (34.8% vs 23.7%; P=.001), likely because of syphilis coinfection. Stillbirth rates were higher for women living with HIV from 2008 to 2014; however, a steady plateau was reached from 2014 to 2018, mirroring stillbirth rates in women without HIV. Maternal HIV infection did not increase the risk of miscarriage (relative risk, 0.90; 95% confidence interval, 0.77-1.05) or any pregnancy loss (relative risk, 1.00; 95% confidence interval, 0.88-1.15), but was associated with stillbirth (relative risk, 1.65; 95% confidence interval, 1.23-2.21). Maternal syphilis was associated with any pregnancy loss (relative risk, 1.24; 95% confidence interval, 1.11-1.38) and stillbirth (relative risk, 3.39; 95% confidence interval, 2.77-4.14), but not miscarriage (relative risk, 0.91; 95% confidence interval, 0.80-1.04). CONCLUSION: In the era of combination antiretroviral therapy, there was no difference in miscarriage rates between women with and without HIV. HIV was associated with stillbirth risk but improved over time. Maternal syphilis was significantly associated with any pregnancy loss and stillbirth in all women. Syphilis is likely the main driver of pregnancy loss in women living with HIV in Brazil.

Ineffective penicillin treatment and absence of partner treatment may drive the congenital syphilis epidemic in Brazil.

BACKGROUND: Reducing congenital syphilis has been the focus of Brazilian health programs for decades, yet the cases continue to increase. Although health interventions have targeted HIV screening and treatment, syphilis management continues to be challenging. Syphilis during pregnancy may enhance the HIV maternal seroconversion risk. The potential factors fueling the syphilis epidemic were evaluated in south Brazil, an area of high HIV or syphilis endemicity. OBJECTIVE: We hypothesized that ineffective treatment because of a lack of partner treatment, late presentation to care, and reinfection of previously treated mothers were potential drivers of syphilis mother-to-child transmission. STUDY DESIGN: Data on women diagnosed with syphilis during pregnancy between January 1, 2008 and December 31, 2018 were obtained from a large urban hospital in Porto Alegre, Brazil. The patients were stratified into effective vs ineffective treatment groups according to the World Health Organization guidelines. Crude and adjusted risk ratios for the prediction of congenital syphilis and adverse fetal or neonatal outcomes were computed using Poisson regression. RESULTS: Nearly 56,000 pregnant women delivered over the 11-year period; 1541 (2.8%) had confirmed syphilis during pregnancy, with 934 (61%) receiving ineffective syphilis treatment because of late presentation and diagnosis, delayed treatment initiation, and loss to follow-up with no treatment recorded. Ineffective treatment was associated with maternal education, prenatal care, timing of syphilis diagnosis, venereal diseases research laboratory titers, and maternal HIV coinfection. On multivariate regression analysis, ineffective treatment (adjusted risk ratio, 4.52; 95% confidence interval, 2.35-8.69), absence of prenatal care (adjusted risk ratio, 9.31; 95% confidence interval, 3.77-23.0), syphilis diagnosis at delivery (adjusted risk ratio, 3.08; 95% confidence interval, 2.07-4.58), and maternal nontreponemal titers ≥1:64 (1.09-1.93) were associated with an increased risk of fetal loss. Ineffective treatment (adjusted risk ratio, 1.71; 95% confidence interval, 1.59-1.84), year of diagnosis 2014 to 2016 (adjusted risk ratio, 1.07; 95% confidence interval, 1.02-1.13), absence of prenatal care (adjusted risk ratio, 1.44; 95% confidence interval, 1.17-1.76), and maternal nontreponemal titers >1:4 were associated with an increased risk of congenital syphilis. Although partner treatment reduced the congenital syphilis risk (adjusted risk ratio, 0.60; 95% confidence interval, 0.55-0.66), only 31.8% of partners received treatment. Maternal HIV coinfection was not associated with an increased risk of fetal loss, low birthweight, preterm birth, congenital syphilis, or symptomatic neonatal infection. CONCLUSION: Public health initiatives promoting effective syphilis treatment in pregnancy, increased access to high-quality prenatal care, and partner treatment should be considered to reduce congenital syphilis.

Prospective cohort study of children exposed to hepatitis C virus through a pregnancy screening program.

OBJECTIVES: Porto Alegre, in south Brazil, has one of the highest hepatitis C virus (HCV) infection rates in the country (84.4 cases/100 000 in 2018). Prenatal screening of HCV, however, has not been routinely offered. METHODS: A longitudinal study of pregnant women with HCV and their infants was conducted between January 2014 and December 2018. Screening for HCV antibodies was offered to all women delivering at the study tertiary institution. HCV RT-PCR was performed if the woman was seropositive. Infants were followed prospectively. RESULTS: Among 18 953 pregnant women delivering infants during the study period, 17 810 were screened for HCV antibodies (93.9%) with 130 positive results (HCV seroprevalence 0.7%). HCV-RNA was detectable in 57/117 cases (48.7%). HCV viremia was associated with the use of injectable drugs (P = 0.03), inhaled/crack drug use (P = 0.02), having an HCV-seropositive partner, and ≥3 lifetime sexual partners (P < 0.01). Genotype 1 was most prevalent (68%) during pregnancy. Among 43 children with follow-up, six (13%) were HCV-infected (transmission rate 13.9%); 50% were infected with genotype 3. Two infants (33%) cleared their infection; the mothers had genetic polymorphisms associated with clearance. CONCLUSION: HCV vertical transmission was high in the study population, with HCV infection during pregnancy being vastly underdiagnosed. Public health efforts must focus on this vulnerable population for disease prevention and early treatment.

Increased IL-8 levels in HIV-infected individuals who initiated ART with CD4+ T cell counts <350 cells/mm3 - A potential hallmark of chronic inflammation.

The identification of inflammatory markers in HIV+ individuals on ART is fundamental since chronic ART-controlled HIV infection is linked to an increased inflammatory state. In this context, we assessed plasma levels of pro-inflammatory cytokines (IL-1ß, IL-8, and IL-12p70) of HIV+ individuals who initiated ART after immunosuppression (CD4+ T cell counts <350 cells/mm3). HIV+ individuals were stratified according to two extreme phenotypes: Slow Progressors (SPs; individuals with at least 8 years of infection before ART initiation) and Rapid Progressors (RPs; individuals who needed to initiate ART within 1-4 years after infection). A control group was composed of HIV-uninfected individuals. We found increased IL-8 levels (median: 5.13 pg/mL; SPs and RPs together) in HIV-infected individuals on ART as compared to controls (median: 3.2 pg/mL; p = 0.04), although no association with the progression profile (slow or rapid progressors) or CD4+ T cell counts at sampling was observed. This result indicates that IL-8 is a general marker of chronic inflammation in HIV+ individuals on ART, independently of CD4+ T cell counts at the beginning of the treatment or of the potential progression profile of the patient. In this sense, IL-8 may be considered a possible target for novel therapies focused on reducing inflammation in chronic HIV infection.

Sexual transmission of HIV-1 among serodiscordant couples in Porto Alegre, southern Brazil.

BACKGROUND: A cohort of 93 heterosexual HIV serodiscordant couples with no prior antiretroviral use were identified in a large referral center from February 2000 to January 2006 in southern Brazil. METHODS: Review of clinic records retrospectively identified 56 cases of untreated index cases whereas 37 couples were identified prospectively. Demographics, medical, and laboratory data were obtained. During follow-up, 41/93 index cases (44%) initiated antiretrovirals (ARVs) and from 52 without ARV use, 4 were lost to follow-up. Median viral loads were used to compare transmitters versus nontransmitters (Mann-Whitney test). RESULTS: Sixty-seven (72%) index cases were female (49% identified during ante-natal care). Unprotected sexual intercourse as a risk factor for HIV-1 infection was significantly higher as compared to intravenous drug use (P < 0.0001) in female index partners but not in male index cases. Sexually transmitted diseases were identified in 22 cases (24%). Six HIV-1 seroconversions occurred (6.5%). In all cases index partners were not using ARVs at the time of seroconversion. Among 26 couples with a male index case, there were 4 seroconversions (15%) and among 67 female index cases there were 2 seroconversions (3%). All seroconversions occurred with virus loads >1000 copies/mL. Eight female index cases (22%) reported no condom use. CONCLUSIONS: Heterosexual transmission occurred more frequently from HIV-infected males to females (rate ratio 3.5; CI, 95% 0.8-16.5 P = 0.259), although without statistical significance, probably because of the small sample. Transmitters showed significantly higher median viral loads (P = 0.042) suggesting that heterosexual transmission of HIV is more a function of viral load than gender of index case. ARV use may play a role in the prevention of HIV-1 heterosexual transmission. Other factors may be involved and should be further evaluated in larger cohorts.

High CXCL10/IP-10 levels are a hallmark in the clinical evolution of the HIV infection.

The aim of this study was to investigate the modulation of plasma CXCL10, CCL20, CCL22, CCL2, CCL17 and CCL24 levels in HIV-positive patients grouped according to extreme phenotypes of progression to AIDS, and at different stages of HIV infection. HIV-positive individuals with extreme phenotypes of AIDS progression (n=58) at different clinical stages (chronic individuals, both pre-HAART and under-HAART) and HIV-negative controls (n=20) were evaluated. Additionally, HIV-positive individuals that initiated HAART with >350CD4+T-cells/mm3 were compared with those who initiated treatment with <350CD4+T-cells/mm3. Plasma levels of six chemokines were quantified by a Luminex assay. Higher CXCL10 levels were observed in individuals immediately before their CD4+T-cell levels were indicative for HAART (pre-HAART), independently of their progressor status, i.e. slow (SPs) or rapid progressors (RPs). SPs pre-HAART showed higher CXCL10 levels compared to elite controllers and RPs under HAART (pc=0.009 and pc=0.007, respectively). CXCL10 levels were higher in SPs HAART CD4<350 (initiated HAART with <350 CD4+T-cells) when compared with SPs HAART CD4>350 (initiated HAART with >350 CD4+T-cells) (1096 vs. 360.33pg/mL, p=0.0101). Normalisation of CXCL10 levels seems to depend on the CD4+T-cell nadir at HAART initiation. CCL20 levels were higher in chronic SPs, SPs pre-HAART, SPs HAART and RPs HAART compared with the HIV-negative controls, indicating persistent CCL20 expression. In conclusion, our results indicate that CXCL10 levels are a hallmark in the clinical evolution of HIV infection. However, our results must be verified in a study evaluating a larger number of AIDS progressors.

[Evaluation of the cellular immunity in patients coinfected by the hepatitis C virus and the human immunodeficiency virus]. / Avaliação da imunidade celular nos pacientes Co-Infectados pelo vírus da hepatite C e vírus da imunodeficiência humana.

BACKGROUND: The immune activation provoked by the hepatitis C virus can be deleterious in patients with human immunodeficiency virus, favouring the destruction of CD4 cells. By the other side, the immune restoration observed after the onset of antiretroviral therapy can be partially obscured in patients with the hepatitis C virus. AIM: The objective of the present study was to evaluate the impact of coinfection by hepatitis C virus and the human immunodeficiency virus in the cellular immunity. METHODS: Two groups of patients were considered: coinfected patients were prospectively evaluated in the gastroenterology clinic at "Hospital Nossa Senhora da Conceição", Porto Alegre, RS, Brazil (group 1 - 385 patients), and monoinfected patients by human immunodeficiency virus based on the review of the charts from the infectious diseases clinic (group 2 - 198 patients). Demographic (gender, race, age) CD4 and CD8 cell count, CD4/CD8 index and human immunodeficiency virus viral load were evaluated. A 5% significance level was adopted. RESULTS: There were no difference between the parameters evaluated: mean CD4 count (374,7 +/- 215,7 x 357,5 +/- 266,0), CD8 (1.512,4 +/- 7.274,6 x 986,7 +/- 436,4) and HIV viral load (83.744,2 +/- 190.292,0 x 104.464,0 +/- 486.880,5) respectively in both groups evaluated, as well as the proportion of patients with CD4/CD8 rate below 1. CONCLUSION: Coinfection by both viruses did not have a negative impact in relation to monoinfection by human immunodeficiency virus, and the immune profile was similar in all groups.

Virologic outcomes in early antiretroviral treatment: HPTN 052.

INTRODUCTION: The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. OBJECTIVE: To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. METHODS: 1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350-550 cells/mm3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4 < 250 cells/mm3 at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤ 400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs > 1000 copies/mL > 24 weeks after ART initiation. RESULTS: Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure. CONCLUSIONS: Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention.

[Ambulatorial prevalence of hepatitis B and C markers in patients with human immunodeficiency virus infection in a general hospital]. / Prevalência ambulatorial em um hospital geral de marcadores para hepatites B e C em pacientes com infecção pelo vírus da imunodeficiência humana.

BACKGROUND: Hepatitis B and C viruses and human immunodeficiency virus share the same route of transmission, and the prevalence of HBV and HCV infection in patients infected with HIV is greater than it is in the general population. AIM: To determine the prevalence of hepatitis B and C markers in a population of patients with HIV as well as the risk factors involved. PATIENTS AND METHODS: From 5,870 registration forms of patients with HIV of an Infectology Unit, 587 were randomly selected. From these, the 343 which had investigated the presence of any hepatitis B (HBsAg, anti-HBc or anti-HBs) or C (anti-HCV) marker were retrospectively analyzed. RESULTS: HBsAg was positive in 14/306 (4.6%), anti-HBs was positive in 40/154(26.0%), and anti-HBc in 79/205 (38.5%). The anti-HCV test was reactive in 126/330 (38.2%). HBV and HCV co-infection was observed in 7 of the 296 patients who had both HBsAg and anti-HCV tests (2.4%). For those who were HBsAg positive, the main exposure factor was homosexual intercourse (50.0%). For those who were anti-HCV reactive, the main risk factor was intravenous drug use (75.3%). In the HIV mono-infected (185 patients), the most prevalent exposure risk factor was promiscuous heterosexual practices or sexual intercourse with a spouse infected with HIV (83 patients - 44.9%). CONCLUSION: In our environment HBV-HIV and HCV-HIV co-infections are frequent, a greater relevance being observed in the association between HCV and HIV.

Retrospective study of 668 cultures for mycobacteria in a reference hospital for AIDS in southern Brazil.

Although AIDS patients in other countries are frequently diagnosed as having atypical mycobacterial infection, in Southern Brazil there is a clinical impression that Mycobacterium tuberculosis is the rule rather than the exception. We made a retrospective review of cultures for mycobacteria at our hospital in order to determine the frequency of atypical mycobacteria and Mycobacterium tuberculosis in hospitalised patients in Porto Alegre, Brazil. Mycobacterium tuberculosis was the most frequent isolate (79.9%), regardless of HIV serostatus. Only 1.5% of the cultures yielded atypical mycobacteria, all of which in AIDS patients. Mycobacterium tuberculosis was diagnosed in most of the HIV-infected patients (81.2%). We conclude that Mycobacterium tuberculosis is frequent in both HIV infected and non-HIV infected patients in this part of the country.

Raltegravir for the treatment of patients co-infected with HIV and tuberculosis (ANRS 12 180 Reflate TB): a multicentre, phase 2, non-comparative, open-label, randomised trial.

BACKGROUND: Concurrent treatment of HIV and tuberculosis is complicated by drug interactions. We explored the safety and efficacy of raltegravir as an alternative to efavirenz for patients co-infected with HIV and tuberculosis. METHODS: We did a multicentre, phase 2, non-comparative, open-label, randomised trial at eight sites in Brazil and France. Using a computer-generated randomisation sequence, we randomly allocated antiretroviral-naive adult patients with HIV-1 and tuberculosis (aged ≥18 years with a plasma HIV RNA concentration of >1000 copies per mL) to receive raltegravir 400 mg twice a day, raltegravir 800 mg twice daily, or efavirenz 600 mg once daily plus tenofovir and lamivudine (1:1:1; stratified by country). Patients began study treatment after the start of tuberculosis treatment. The primary endpoint was virological suppression at 24 weeks (HIV RNA <50 copies per mL) in all patients who received at least one dose of study drug (modified intention-to-treat analysis). We recorded death, study drug discontinuation, and loss to follow-up as failures to achieve the primary endpoint. We assessed safety in all patients who received study drugs. This study is registered in ClinicalTrials.gov, number NCT00822315. FINDINGS: Between July 3, 2009, and June 6, 2011, we enrolled and randomly assigned treatment to 155 individuals; 153 (51 in each group) received at least one dose of the study drug and were included in the primary analysis. 133 patients (87%) completed follow-up at week 48. At week 24, virological suppression was achieved in 39 patients (76%, 95% CI 65-88) in the raltegravir 400 mg group, 40 patients (78%, 67-90) in the raltegravir 800 mg group, and 32 patients (63%, 49-76) in the efavirenz group. The adverse-event profile was much the same across the three groups. Three (6%) patients allocated to efavirenz and three (6%) patients allocated to raltegravir 800 mg twice daily discontinued the study drugs due to adverse events. Seven patients died during the study (one in the raltegravir 400 mg group, four in the raltegravir 800 mg group, and two in the efavirenz group): none of the deaths was deemed related to study treatment. INTERPRETATION: Raltegravir 400 mg twice daily might be an alternative to efavirenz for the treatment of patients co-infected with HIV and tuberculosis. FUNDING: French National Agency for Research on AIDS and Viral Hepatitis (ANRS), Brazilian National STD/AIDS Program-Ministry of Health.

Immune restoration in human immunodeficiency virus and hepatitis C virus coinfected patients after highly active antiretroviral therapy.

OBJECTIVE: To evaluate the influence of hepatitis C virus on immunological and virological responses after highly active antiretroviral therapy initiation in human immunodeficiency virus/hepatitis C virus coinfected patients compared to monoinfected human immunodeficiency virus-infected patients. METHODS: The study enrolled 65 human immunodeficiency virus-1-infected subjects who initiated highly active antiretroviral therapy and attended follow-up visits over 48 weeks from 2008 to 2010. They were grouped based on hepatitis C virus-RNA results. Virological and immunological responses were monitored at baseline and at the end of weeks 12, 24, 36, and 48. RESULTS: There were 35 human immunodeficiency virus monoinfected and 30 human immunodeficiency virus/hepatitis C virus coinfected patients. In the present study human immunodeficiency virus/hepatitis C virus coinfection did not seem to influence CD4 T-lymphocytes recovery. There was no difference between the curves of CD4 T-lymphocytes raise of coinfected and monoinfected groups. CONCLUSION: This prospective study confirms that hepatitis C virus infection does not seem to be associated with impaired CD4 T-lymphocytes recovery after HAART.

Enterococcus gallinarum meningitis in an immunocompetent host: a case report.

We describe a rare case of a 53-year-old man with a long history of alcohol abuse, with Enterococcus gallinarum meningitis, an organism that rarely causes human infection and is primarily found in the gastrointestinal tract of poultry. The patient improved with high-dose ampicillin and gentamicin therapy. To our knowledge, this is the first Brazilian reported case of E. gallinarum meningitis and probably the first case described in an immunocompetent host.

Treatment of severe chromoblastomycosis with itraconazole and 5-flucytosine association.

Chromoblastomycosis is a chronic human melanized fungi infection of the subcutaneous tissue caused by traumatic inoculation of a specific group of dematiaceous fungi through the skin, often found in barefooted agricultural workers, in tropical and subtropical climate countries. We report the case of a male patient presenting a slow-growing pruriginous lesion on the limbs for 20 years, mistreated over that time, which was diagnosed and successfully treated as chromoblastomycosis. Besides the prevalence of this disease, treatment is still a clinical challenge.

[Evaluation of APRI score in liver disease following the introduction of antiretroviral therapy in HIV and HCV coinfected versus HIV monoinfected patients]. / Uso do score APRI na avaliação de doença hepática, após início de terapia antirretroviral, em pacientes portadores do HIV co-infectados com HCV versus monoinfectados por HIV.

INTRODUCTION: The impact of highly active antiretroviral therapy (HAART) on hepatic fibrosis progression in HIV and hepatitis C virus coinfected patients is not completely understood. Noninvasive hepatic fibrosis markers show great promise in determining liver fibrosis staging and monitoring disease progression. METHODS: Twenty-four patients divided equally into two groups: 12 HIV-monoinfected and 12 with HIV/HCV coinfected patients, were followed from July 2008 to August 2009, after initiating HAART, with clinical, epidemiological and laboratorial assessments every 3 months and calculation of the aspartate aminotransferase to platelet ratio index (APRI). This study aimed to compare the progression of APRI, a noninvasive hepatic fibrosis marker, among populations with HIV and HIV/HCV coinfection. RESULTS: No differences were observed between the groups regarding age, sex, measurement of CD4 and HIV viral load in all consultations, type of HAART and APRI before initiating HAART. Coinfected patients showed a significantly higher APRI than the monoinfected group in month 3 (0.57 ± 0.31 x 0.27 ± 0.105, p = 0.02) and 6 (0.93 ± 0.79 x 0.28 ± 0.11, p = 0.04). CONCLUSIONS: In the present study, HAART was associated with APRI increases over six months follow-up in HIV/HCV coinfected patients, suggesting that these may be experiencing cumulative hepatotoxicity and immune reconstitution inflammatory syndrome after initiating antiretroviral drugs.