Preliminary comparative study of cortical thickness in HIV-infected patients with and without working memory deficit.

PURPOSE: Changes in cerebral cortical regions occur in HIV-infected patients, even in those with mild neurocognitive disorders. Working memory / attention is one of the most affected cognitive domain in these patients, worsening their quality of life. Our objective was to assess whether cortical thickness differs between HIV-infected patients with and without working memory deficit. METHODS: Forty-one adult HIV-infected patients with and without working memory deficit were imaged on a 1.5 T scanner. Working memory deficit was classified by composite Z scores for performance on the Digits and Letter-Number Sequencing subtests of the Wechsler Adult Intelligence Scale (third edition; WAIS-III). Cortical thickness was determined using FreeSurfer software. Differences in mean cortical thickness between groups, corrected for multiple comparisons using Monte-Carlo simulation, were examined using the query design estimate contrast tool of the FreeSurfer software. RESULTS: Greater cortical thickness in left pars opercularis of the inferior frontal gyrus, and rostral and caudal portions of the left middle frontal gyrus (cluster 1; p = .004), and left superior frontal gyrus (cluster 2; p = .004) was observed in HIV-infected patients with working memory deficit compared with those without such deficit. Negative correlations were found between WAIS-III-based Z scores and cortical thickness in the two clusters (cluster 1: ρ = -0.59; cluster 2: ρ = -0.47). CONCLUSION: HIV-infected patients with working memory deficit have regions of greater thickness in the left frontal cortices compared with those without such deficit, which may reflect increased synaptic contacts and/or an inflammatory response related to the damage caused by HIV infection.

Maternal HIV and syphilis are not syndemic in Brazil: Hot spot analysis of the two epidemics.

While the annual incidence of HIV diagnosis in pregnancy in Brazil remains relatively stable, rates of maternal syphilis increased over six-fold in the past decade. We hypothesized that maternal HIV and syphilis are two distinct epidemics. Data on all cases of maternal HIV or syphilis detected in pregnancy between January 1, 2010 to December 31, 2018 were requested from the Brazilian Ministry of Health. In order to evaluate how the epidemics evolved over the time period, ArcGIS software was used to generate spatiotemporal maps of annual rates of detection of maternal HIV and syphilis in 2010 and 2018. We utilized Euclidean-distance hot spot analysis to identify state-specific clusters in 2010 and 2018. From 2010 to 2018, there were 66,631 cases of maternal HIV, 225,451 cases of maternal syphilis, and 150,414 cases of congenital syphilis in Brazil. The state of Rio Grande do Sul had the highest rate of maternal HIV detection in both 2010 and 2018. Hot spots of maternal HIV were identified in the three most Southern states in both 2010 and 2018 (99% confidence, z-score >2.58, p <0.01). While syphilis incidence >30 per 1,000 live births in 2018 in four states, only the two coastal states of Rio de Janeiro and Espirito Santo in Southeastern Brazil were significant hot spots (90% confidence, z-score 1.65-1.95, p <0.10). Contrary to the general assumption, HIV and syphilis epidemics in Brazil are not syndemic in pregnant women. There is a spatial cluster of maternal HIV in the South, while syphilis is increasing throughout the country, more recently on the coast. Focusing on maternal HIV hot spots in the Southern states is insufficient to curtail the maternal and congenital syphilis epidemics throughout the country. New strategies, including ongoing hot spot analysis, are urgently needed to monitor, identify and treat maternal syphilis.

A call to improve understanding of Undetectable equals Untransmittable (U = U) in Brazil: a web-based survey.

INTRODUCTION: Currently, the slogan "Undetectable = Untransmittable" (U = U), launched to disseminate scientific evidence on how people living with HIV (PLHIV) on antiretroviral treatment with suppressed viral load cannot transmit HIV to their sexual partners, is still challenged by individuals with differential acceptance across populations. In this study, we documented the perceived accuracy of U = U in Brazil in three different groups: PLHIV, HIV-negative/unknown cisgender gay/bisexual men who have sex with men (GBM) and HIV-negative/unknown other populations (POP). METHODS: Adult (age ≥ 18y) Brazilians were recruited during October 2019 to complete a web-based survey advertised on Grindr, Facebook and WhatsApp. Perceived accuracy of U = U was assessed with the question: "With regards to HIV-positive individuals transmitting HIV through sexual contact, how accurate do you believe the slogan U = U is?" Response options ranged from 1 (Completely inaccurate) to 4 (Completely accurate) plus a fifth option (I don't know what "undetectable" means). Participants' characteristics were described according to perceived accuracy of U = U. Logistic regression models assessed the factors associated with perceived accuracy of U = U (completely accurate vs. partially accurate/inaccurate or completely inaccurate) by group. RESULTS: Of 2311 individuals accessing the questionnaire, 1690 (73.1%) met inclusion/exclusion criteria and completed it. Of these, 347 (20.5%) were PLHIV, 785 (46.4%) GBM and 558 (33.0%) POP. More PLHIV perceived U = U as completely accurate (79.0%), compared to 44.2% GBM and 17.2% POP (p < 0.001). Among PLHIV, Black identity was associated with decreased odds of perceiving U = U as completely accurate while having a steady partner was associated with increased odds. Among GBM, being gay, having middle/higher income, being a resident of state capital metropolitan areas and ever testing for HIV were associated with increased odds. Lastly, among POP, ever testing for HIV increased the odds of perceiving U = U as completely accurate. CONCLUSIONS: There was a significant difference in perceived accuracy of U = U across population groups. Accurate understanding of the slogan needs to be promoted in more vulnerable populations such as PLHIV of Black identity and GBM of lower income to maximize individual and societal prevention benefits. Moreover, broader understating of U = U among the general population can help decrease societal stigma towards PLHIV.

HIV and SARS-CoV-2: points to consider to face this new pandemic. / VIH y SARS-CoV-2: aspectos a considerar para enfrentar esta nueva pandemia.

In December 2019, a new species of pneumonia-causing betacoronavirus was identified in Wuhan, China, which was later identified as SARS-CoV-2. This RNA virus presents certain similarities with other viruses of the same genetic material. It has been seen that infection by human immunodeficiency virus resembles the infection by SARS-CoV-2 in various aspects. In this comment, we present some of the virological, immunological, clinical, and pharmacological similarities between HIV and SARS-CoV-2, which could allow us to understand the immunopathogenesis of COVID-19 better, as well as make some decisions in regarding antiviral management.

En diciembre de 2019 una nueva especie de ß-coronavirus causante de neumonía fue identificada en la ciudad China de Wuhan, el cual posteriormente fue denominado SARS-CoV-2. Este virus de ácido ribonucleico presenta ciertas similitudes con otros virus del mismo material genético, dentro de ellos se ha visto que la infección por virus de la inmunodeficiencia humana se asemeja en diversos aspectos a la infección por SARS-CoV-2. En este comentario presentamos algunas de las similitudes virológicas, inmunológicas, clínicas y farmacológicas entre estos dos virus, las cuales podrían permitirnos entender de mejor manera la inmunopatogenia de COVID-19, así como también tomar algunas decisiones en cuanto al manejo antiviral.

VIH y SARS-CoV-2: aspectos a considerar para enfrentar esta nueva pandemia / HIV and SARS-CoV-2: points to consider to face this new pandemic

En diciembre de 2019 una nueva especie de ß-coronavirus causante de neumonía fue identificada en la ciudad China de Wuhan, el cual posteriormente fue denominado SARS-CoV-2. Este virus de ácido ribonucleico presenta ciertas similitudes con otros virus del mismo material genético, dentro de ellos se ha visto que la infección por virus de la inmunodeficiencia humana se asemeja en diversos aspectos a la infección por SARS-CoV-2. En este comentario presentamos algunas de las similitudes virológicas, inmunológicas, clínicas y farmacológicas entre estos dos virus, las cuales podrían permitirnos entender de mejor manera la inmunopatogenia de COVID-19, así como también tomar algunas decisiones en cuanto al manejo antiviral.

In December 2019, a new species of pneumonia-causing betacoronavirus was identified in Wuhan, China, which was later identified as SARS-CoV-2. This RNA virus presents certain similarities with other viruses of the same genetic material. It has been seen that infection by human immunodeficiency virus resembles the infection by SARS-CoV-2 in various aspects. In this comment, we present some of the virological, immunological, clinical, and pharmacological similarities between HIV and SARS-CoV-2, which could allow us to understand the immunopathogenesis of COVID-19 better, as well as make some decisions in regarding antiviral management.

Influence of HIV Infection and Antiretroviral Therapy on Bone Homeostasis.

The human immunodeficiency virus type 1 (HIV)/AIDS pandemic represents the most significant global health challenge in modern history. This infection leads toward an inflammatory state associated with chronic immune dysregulation activation that tilts the immune-skeletal interface and its deep integration between cell types and cytokines with a strong influence on skeletal renewal and exacerbated bone loss. Hence, reduced bone mineral density is a complication among HIV-infected individuals that may progress to osteoporosis, thus increasing their prevalence of fractures. Highly active antiretroviral therapy (HAART) can effectively control HIV replication but the regimens, that include tenofovir disoproxil fumarate (TDF), may accelerate bone mass density loss. Molecular mechanisms of HIV-associated bone disease include the OPG/RANKL/RANK system dysregulation. Thereby, osteoclastogenesis and osteolytic activity are promoted after the osteoclast precursor infection, accompanied by a deleterious effect on osteoblast and its precursor cells, with exacerbated senescence of mesenchymal stem cells (MSCs). This review summarizes recent basic research data on HIV pathogenesis and its relation to bone quality. It also sheds light on HAART-related detrimental effects on bone metabolism, providing a better understanding of the molecular mechanisms involved in bone dysfunction and damage as well as how the HIV-associated imbalance on the gut microbiome may contribute to bone disease.

Costs and economies of scale in the accelerated program for prevention of mother-to-child transmission of HIV in Zimbabwe.

BACKGROUND: Despite a growing body of literature on HIV service costs in sub-Saharan Africa, only a few studies have estimated the facility-level cost of prevention of Mother-to-Child Transmission (PMTCT) services, and even fewer provide insights into the variation of PMTCT costs across facilities. In this study, we present the first empirical costs estimation of the accelerated program for the prevention of mother-to-child transmission of HIV in Zimbabwe and investigate the determinants of heterogeneity of the facility-level average cost per service. To understand such variation, we explored the association between average costs per service and supply-and demand-side characteristics, and quality of services. One aspect of the supply-side we explore carefully is the scale of production-which we define as the annual number of women tested or the yearly number of HIV-positive women on prophylaxis. METHODS: We collected rich data on the costs and PMTCT services provided by 157 health facilities out of 699 catchment areas in five provinces in Zimbabwe for 2013. In each health facility, we measured total costs and the number of women covered with PMTCT services and estimated the average cost per woman tested and the average cost per woman on either ARV prophylaxis or ART. We refer to these facility-level average costs per service as unitary costs. We also collected information on potential determinants of the variation of unitary costs. On the supply-side, we gathered data on the scale of production, staff composition and on the types of antenatal and family planning services provided. On the demand side, we measured the total population at the catchment area and surveyed eligible pairs of mothers and infants about previous use of HIV testing and prenatal care, and on the HIV status of both mothers and infants. We explored the determinants of unitary cost variation using a two-stage linear regression strategy. RESULTS: The average annual total cost of the PMTCT program per facility was US$16,821 (median US$8,920). The average cost per pregnant woman tested was US$80 (median US$47), and the average cost per HIV-positive pregnant woman initiated on ARV prophylaxis or treatment was US$786 annually (median US$420). We found substantial heterogeneity of unitary costs across facilities regardless of facility type. The scale of production was a strong predictor of unitary costs variation across facilities, with a negative and statistically significant correlation between the two variables (p<0.01). CONCLUSIONS: These findings are the first empirical estimations of PMTCT costs in Zimbabwe. Unitary costs were found to be heterogeneous across health facilities, with evidence consistent with economies of scale.

Development and validation of a simple and rapid way to generate low volume of plasma to be used in point-of-care HIV virus load technologies

ABSTRACT A new point-of-care HIV viral load, mPIMA HIV-1/2 VL, Abbott, USA, has been recently developed. This point-of-care viral load requires no skilled person to run and uses a small plasma volume (50 µL). However, obtaining 50 µL of plasma can be a challenge in limited resource settings. We validated a simple and easy method to obtain enough amount of plasma to run a point-of-care viral load. The study utilized 149 specimens from patients failing antiretroviral therapy. At least 250 µL of whole blood was collected in a microtube/EDTA from fingerstick (fs-plasma) and immediately centrifuged. Parallel collection of venous blood to obtain plasma (vp-plasma) was used to compare performance in a point-of-care viral load assay and in methodology used in centralized laboratories Abbott M2000, Abbott, USA. The procedure for plasma collection takes less than 10 min and in 94% of the cases only one fingerstick was sufficient to collect at least 250 µL of blood. The Pearson correlation coefficient value for vp-plasma versus fs-plasma ran on mPIMA was 0.990. The Bland-Altman mean difference (md) for this comparison were virtually zero (md = −0.001) with limits of agreement between −0.225 and 0.223. In addition, the Pearson correlation coefficient value for fs-plasma in mPIMA versus vp-plasma in Abbott M2000 was 0.948 for values above the mPIMA limit of quantification (LoQ; from 800 to 1,000,000 copies/mL). These results validate this simple plasma isolation method capable to be implemented in low resource countries where point-of-care decentralization is deeply needed.

Hepatitis B and C virus infection among HIV patients within the public and private healthcare systems in Chile: A cross-sectional serosurvey.

BACKGROUND: Coinfections of HIV patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) are mayor public health problems, contributing to the emerging burden of HIV-associated hepatic mortality. Coinfection rates vary geographically, depending on various factors such as predominant transmission modes, HBV vaccination rates, and prevalence of HBV and HCV in the general population. In South America, the epidemiology of coinfections is uncertain, since systematic studies are scarce. Our study aimed to analyze rates of HBV and HCV infection in people living with HIV attending centers of the public and private health system in Chile. METHODS: We performed a cross-sectional study including a public university hospital and a private health center in Santiago, Metropolitan Region in Chile. Serum samples were used to determine serological markers of hepatitis B (HBsAg, anti-HBs, anti-HBc total, HBeAg, anti-HBe) and anti-HCV. Demographic, clinical and laboratory data were obtained from medical records. RESULTS: 399 patients were included (353 from public, 46 from private health center). Most (92.8%) were male, with a median age of 38.3 years; 99.4% acquired HIV through sexual contact (75.0% MSM); 25.7% had AIDS and 90.4% were on ART. In 78.9%, viral loads were <40 cps/mL; the median CD4 cell count was 468 cells/mm3. According to their serological status, 37.6% of patients were HBV naïve (susceptible), 6.5% were vaccinated, 43.6% had resolved HBV infection, and 5.8% were chronically infected. The rate of vaccination was 4.5% in the public and 21.7% in the private system. HCV coinfection was found in 1.0% of all patients. CONCLUSION: HBV coinfection rate was within the range of other South American countries, but lower than in non-industrialized regions in Asia and Africa. A low percentage of patients were HBV vaccinated, especially within the public system. HCV coinfection rate was very low, most probably due to the rareness of injecting drug use.

Development and validation of a simple and rapid way to generate low volume of plasma to be used in point-of-care HIV virus load technologies.

A new point-of-care HIV viral load, mPIMA HIV-1/2 VL, Abbott, USA, has been recently developed. This point-of-care viral load requires no skilled person to run and uses a small plasma volume (50µL). However, obtaining 50µL of plasma can be a challenge in limited resource settings. We validated a simple and easy method to obtain enough amount of plasma to run a point-of-care viral load. The study utilized 149 specimens from patients failing antiretroviral therapy. At least 250µL of whole blood was collected in a microtube/EDTA from fingerstick (fs-plasma) and immediately centrifuged. Parallel collection of venous blood to obtain plasma (vp-plasma) was used to compare performance in a point-of-care viral load assay and in methodology used in centralized laboratories Abbott M2000, Abbott, USA. The procedure for plasma collection takes less than 10min and in 94% of the cases only one fingerstick was sufficient to collect at least 250µL of blood. The Pearson correlation coefficient value for vp-plasma versus fs-plasma ran on mPIMA was 0.990. The Bland-Altman mean difference (md) for this comparison were virtually zero (md=-0.001) with limits of agreement between -0.225 and 0.223. In addition, the Pearson correlation coefficient value for fs-plasma in mPIMA versus vp-plasma in Abbott M2000 was 0.948 for values above the mPIMA limit of quantification (LoQ; from 800 to 1,000,000copies/mL). These results validate this simple plasma isolation method capable to be implemented in low resource countries where point-of-care decentralization is deeply needed.

Screening for HBV, HCV, HIV and syphilis infections among bacteriologically confirmed tuberculosis prisoners: An urgent action required.

Viral hepatitis, syphilis, HIV, and tuberculosis infections in prisons have been identified globally as a public health problem. Tuberculosis (TB) and viral hepatitis co-infection may increase the risk of anti-tuberculosis treatment-induced hepatotoxicity, leading to the frequent cause of discontinuation of the first-line anti-tuberculosis drugs. Therefore, the aim of this cross-sectional study was to investigate the epidemiological features of HCV, HBV, syphilis and HIV infections among bacteriologically confirmed tuberculosis prisoners in Campo Grande (MS), Central Brazil. The participants who agreed to participate (n = 279) were interviewed and tested for the presence of active or current HCV, HBV, syphilis and HIV infections. The prevalence of HCV exposure was 4.7% (13/279; 95% CI 2.2-7.1). HCV RNA was detected in 84.6% (11/13) of anti-HCV positive samples. Out of 279 participants, 19 (6.8%; 95% CI 4.4-10.4) were HIV co-infected, 1.4% (4/279, 95% CI 0.5-3.8) had chronic hepatitis B virus (HBsAg positive) and 9.3% (26/279, 95% CI 6.4-13.4) had serological marker of exposure to hepatitis B virus (total anti-HBc positive). The prevalence of lifetime syphilis infection (anti-T. pallidum positive) was 10% (28/279, 95% CI 7.0-14.2) and active syphilis (VDRL ≥ 1/8 titre) was 5% (14/279, 95% CI 2.9-8.3). The prevalence of TB/HCV co-infection among prisoners with HIV (15.8%) was higher than among HIV-non-infected prisoners (3.8%; P<0.05). These results highlight the importance of hepatitis testing among prisoners with bacteriologically confirmed case of TB who can be more effectively and safely treated in order to reduce the side effects of hepatotoxic anti-TB drugs.

Influence of Hepatitis C virus coinfection on immune reconstitution in HIV subjects.

Despite successful HIV suppression by antiretroviral treatment (ART), immune activation may persist in HIV patients, contributing to an impaired immunological reconstitution and disease progression. Information regarding Hepatitis C virus (HCV) coinfection as a factor that accounts for immune activation in HIV subjects remains unclear. Furthermore, most studies have been carried out considering HIV/HCV patients as a whole, without taking into account the presence or absence of liver damage. Therefore, it is unknown if HCV and/or its liver-related disease could act as two independent factors contributing to the immune activation. In this study, we investigated the presence of immune activation in a cohort of 50 HIV/HCV patients by measuring cytokine levels, CD4+ T-cell counts and CD4/CD8 ratios. Six patient groups were defined according to HIV viral load, HCV status, and liver disease to assess the impact of each of these factors on immune activation and reconstitution in HIV/HCV patients. Only subjects with controlled HIV infection and cleared HCV displayed immunological parameters within normal ranges. The mere presence of HCV contributes to immune activation leading to an inappropriate immunological reconstitution. This state exacerbates in the presence of HCV-associated liver disease. Our results suggest that ART is not enough to suppress immune activation in the context of HIV/HCV coinfection, since both HCV and its liver-related disease would contribute to the immune activation. Given that immune activation worsens immunological reconstitution and clinical status, these results support the priority of HCV treatment in HIV/HCV patients and suggest the monitoring of their liver status.

HspBP1 and anti-HspBP1 levels in the serum of HIV-infected individuals are associated to the disease progression.

AIMS: The objective of this research was to quantify the levels of circulating HspBP1 and anti-HspBP1 IgG in HIV-infected individuals and to correlate them with CD4 T cell counts and viral load, as well as to determine the kinetics of those proteins during acute phase. METHODS AND RESULTS: Sixty serum samples from HIV-positive outpatients, thirty with high viral load and thirty with low viral load were analysed. The HspBP1 and anti-HspBP1 were quantified by ELISA. To investigate the kinetic of HspBP1 and anti-HspBp1 during the acute phase, these proteins and antibodies were quantified in samples of a commercial seroconverting HIV panel. All dosages were compared with the CD4 and CD8 T cell counts and HIV viral load. The results indicated that HIV positive outpatients presented significant increase in HspBP1 and anti-HspBP1 serum levels, compared with uninfected healthy. HspBP1 and anti-HspBP1 were negatively correlated with CD4 counts and CD4:CD8 ratio. In the acute phase, HspBP1 became significantly elevated 15 days after HIV infection. CONCLUSIONS: These results indicate that the quantification of HspBP1 can be associated to others well-established parameters of the HIV progression. SIGNIFICANCE AND IMPACT OF THE STUDY: The discovery that HspBp1 and anti-HspBp1 are associated with progression of HIV infection is new and corroborates to validate the quantification of these proteins as an additional strategy in the management of the HIV infection.

Cancer immunotherapy of patients with HIV infection.

Cancer immunotherapy with antibodies against immune checkpoints has made impressive advances in the last several years. The most relevant drugs target programmed cell death 1 (PD-1) expressed on T cells or its ligand, the programmed cell death ligand 1 (PD-L1), expressed on cancer cells, and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Unfortunately, cancer patients with HIV infection are usually excluded from cancer clinical trials, because there are concerns about the safety and the anti-tumoral activity of these novel therapies in patients with HIV infection. Several retrospective studies and some case reports now support the notion that antibodies against immune checkpoints are safe and active in cancer patients with HIV infection, but prospective data in these patients are lacking. In addition, signs of antiviral activity with increase in CD4 T cell counts, plasma viremia reduction or decrease in the viral reservoir have been reported in some of the patients treated, although no patient achieved a complete clearance of the viral reservoir. Here we briefly summarize all clinical cases reported in the literature, as well as ongoing clinical trials testing novel immunotherapy drugs in cancer patients with HIV infection.

Epidemiología molecular de la criptococosis en un Hospital de enfermedades infecciosas de la Ciudad de Buenos Aires: análisis de 25 años / Molecular epidemiology of cryptococcosis in an infectious diseases hospital from the city of Buenos Aires: A 25 years experience

La criptococosis es una micosis grave de distribución universal, que afecta principalmente a huéspedes inmunocomprometidos. Es una de las principales causas de morbilidad y mortalidad en los pacientes infectados con el virus de la inmunodeficiencia humana (HIV). Provoca al menos 620 000 muertes al año, representando entre el 13% al 44% de la mortalidad en pacientes HIV positivos según datos de cohortes correspondientes a países en desarrollo. (1, 2) La letalidad de la criptococosis meníngea en estudios de Argentina y Brasil muestra valores que van desde el 26% hasta el 63%. El complejo Cryptococcus neoformans/ Cryptococcus gattii, es el responsable de esta enfermedad. Existen alrededor de 70 especies pero solo dos de ellas son patógenas para el hombre: C. neoformans y C. gattii. Se reconocen 8 genotipos de este complejo, C. neoformans: VNI y VNII (C. neoformans var. grubii), VNIII (C. neoformans híbrido intervariedad AD), VNIV (C. neoformans var. neoformans) y C. gattii: genotipos VGI, VGII, VGIII y VGIV. Se han descripto híbridos interespecie VNIV/VGI, VNI/VGI, VNI/VGII. Se estudiaron 207 aislamientos de Cryptococcus, elegidos aleatoriamente, de un total de 2593 pacientes con diagnóstico de criptococosis diseminada. A los mismos se les realizó la genotipificación mediante una PCR-RFLP del gen URA5, y posterior digestión enzimática con enzimas Sau96I y HhaI. De las 207 cepas estudiadas, 174 fueron VNI (84,05%), 14 VNII (6,76%), 10 VNIII (4,83%), 2 VNIV (0,97%), 3 VGI (1,45%), 3 VGII de (1,45%) y 1 VGIII (0,49%).

Cryptococcosis is a severe worldwide mycosis, which mainly affects immunocompromised hosts and is a major cause of morbidity and mortality in HIV-infected patients. It causes 620,000 annual deaths, accounting for 13-44 % of mortality in HIV-positive individuals in developing countries. Mortality rates of meningeal cryptococcosis in studies from Argentina and Brazil go from 26 to 63 %. Cryptococcus neoformans/Cryptococcus gattii is the species complex responsible for this disease. There are about 70 species, however, only two are human pathogens: C. neoformans and C. gattii. C. neoformans genotypes are VNI and VNII (C. neoformans var. grubii), VNIII (C. neoformans intervariety hybrid AD), VNIV (C. neoformans var. neoformans). C. gattii genotypes are VGI, VGII, VGIII and VGIV. Interspecies hybrids were described: VNIV/VGI, VNI/VGI, VNI/ VGII. A total of 207 Cryptococcus isolates were randomly selected from 2593 patients with diagnosis of disseminated cryptococcosis. Genotyping was performed by PCRRFLP of UR A5 gene with restriction enzyme digestion using Sau96I and HhaI enzymes. Among the 207 studied isolates, 174 resulted VNI (84.05%), 14 VNII (6.76%), 10 VNIII (4.83%), 2 VNIV (0.97%), 3 VGI (1.45%), 3 VGII (1.45%) and 1 VGIII (0.49%).

Visceral Leishmaniasis in Hospitalized HIV-Infected Patients in Pernambuco, Brazil.

Common in four continents, visceral leishmaniasis (VL) is an important but neglected disease. Human immunodeficiency virus (HIV) infection increases the risk of developing VL in people from leishmaniasis-endemic areas, with worse prognosis when there is coinfection. We conducted a cross-sectional study to determine the prevalence of HIV/VL coinfection in patients admitted in three referral hospitals for HIV/acquired immunodeficiency syndrome (AIDS) in Pernambuco, Brazil, and to compare epidemiological, clinical, and laboratory characteristics among HIV/VL coinfected and HIV mono-infected individuals. The sample consisted of HIV patients aged 18 years or more, in a period of data collection of 6 months. We performed four Leishmania tests-polymerase chain reaction (PCR), direct agglutination test, rK39, and latex agglutination test-and individuals with at least one positive test were considered coinfected. The HIV/VL coinfection prevalence we found was 16.9%. We observed large variation in prevalence according to the Leishmania test used, with low coincidence of positive tests. The most frequent symptoms found were weight loss (75.6%), fever (67.6%), and cough (55.3%). When we compared HIV/VL coinfected and HIV mono-infected groups we did not observe statistically significant differences. Low educational level (P = 0.004) and pallor (P = 0.009) were more frequent in the coinfected group. Serum albumin level was higher in coinfected individuals (P = 0.009). It is important to follow-up these individuals to understand the dynamics of VL in people living with HIV. New tests are necessary, ideally differentiating active from latent infection. Testing for VL in people with HIV is important and should be considered as part of the initial investigation in these individuals.

Comparing HIV risk-related behaviors between 2 RDS national samples of MSM in Brazil, 2009 and 2016.

INTRODUCTION: Periodic monitoring of sociobehavior characteristics at a national level is an essential component of understanding the dynamics the human immunodeficiency virus (HIV) epidemic worldwide, including Brazil. METHODS: This paper compares descriptive sociobehavior characteristics in 2 national cross-sectional HIV biological behavioral surveillance surveys (BBSS) conducted in 2009 and 2016 among men who have sex with men (MSM) in Brazil. Respondent driven sampling (RDS) was used for recruitment in both years. Overall proportions were weighted according to Gile's estimator using RDS Analyst Software and 95% confidence intervals were calculated for comparisons between the 2 periods. Further comparisons were stratified by age groups (<25 and 25+ years old). RESULTS: Overall, 3749 and 4176 MSM were recruited in 2009 and 2016, respectively. In 2016, participants were younger than 25 years old (58.3%), with 12 or more years of education (70.4%), with higher socioeconomic status (40.7%), and had a higher proportion of whites (31.8%), as compared to 2009. Also, participants in 2016 reported less alcohol use and binge drinking, but used illicit drugs more frequently. There was an increase among MSM who self-reported their HIV risk as low and had low HIV knowledge while the proportion of those who were never tested for HIV dropped from 49.8% in 2009 to 33.8% in 2016. Although more than three-quarters received free condoms in both years, STD counseling remained low (32% and 38% for 2009 and 2016, respectively). Sexual risk behavior remained at high levels, especially unprotected anal receptive sex and sex with multiple partners. Younger MSM (<25 years old) showed riskier sexual practices than those 25+ years old, when comparing 2016 to 2009. CONCLUSIONS: Our results indicate a worrisome risk behavior trend among Brazilian MSM, especially among younger ones. These results can contribute for a better understanding of the HIV epidemics in Brazil, with timely shift in strategies so improved effectiveness in public health prevention efforts can be achieved.

Modeling of the HIV epidemic and continuum of care in French Guiana.

BACKGROUND: In order to compute the continuum of care for French Guiana, it is necessary to estimate the total number of persons living with HIV. The main objective was to determine how many persons were infected with HIV and how many were unaware of it. METHODS: We used 2 different models to calculate the total number of persons infected with HIV: Spectrum's AIM module using CSAVR to compute incidence from case registration and vital statistics; and the ECDC model from the French Guiana HIV cohort data. RESULT: The present results show that both models led to similar results regarding the incident number of cases (i.e. for 2016 174 versus 161) and the total HIV population (in 2016 3206 versus 3539) respectively. The ECDC modeling tool showed that the proportion of undiagnosed HIV infections declined from 50% in 1990 to 15% in 2015. This amounted to a stable or slightly increasing total number of undiagnosed patients of 520. CONCLUSIONS: The estimations of the total HIV population by both models show that the HIV population is still growing. The incidence rate declined in 2000 and the decline of the number of newly acquired HIV infections, after a decline after 2003 is offset by population growth. The proportion of undiagnosed infections has declined to 15% but the number of undiagnosed infections remains stable. The HIV cascade shows that despite good results for treatment in care, reaching the 90*90*90 UNAIDS target may be difficult because a significant proportion of patients are lost to follow-up.

Monotypic low-level HIV viremias during antiretroviral therapy are associated with disproportionate production of X4 virions and systemic immune activation.

OBJECTIVE: During effective antiretroviral therapy (ART), low-level plasma viremias (LLV) (HIV RNA >30-1000 copies/ml) can be detected intermittently. We hypothesized that systemic inflammation is associated with LLV either as the cause or result of the production of virions from clonally expanded cells. METHODS: Prospective cohort study of HIV-infected ART-naive Peruvians enrolled prior to ART and followed for 2 years. Plasma HIV RNA and peripheral blood mononuclear cell (PBMC) HIV DNA concentrations were quantified pre-ART from individuals whose plasma HIV RNA was ART-suppressed. Inflammatory biomarker concentrations were measured pre and during ART. Single-genome amplification (SGA) derived HIV env and pol genotypes from pre-ART and LLV specimens. Antiretroviral levels during ART assessed adherence. Statistical associations and phylogenetic relationships were examined. RESULTS: Among 82 participants with median plasma HIV RNA less than 30 copies/ml, LLV were detected in 33 of 82 (40%), with a LLV median HIV RNA of 73 copies/ml. Participants with vs. without LLV had significantly higher pre-ART plasma HIV RNA (P < 0.001) and PBMC HIV DNA (P < 0.007); but, during ART, their antiretroviral drug levels were similar. LLV env sequences were monotypic in 17 of 28 (61%) and diverse in 11 of 28 (39%) participants. Those with the monotypic vs. diverse LLV pattern had elevated hsCRP and sCD163 (P = 0.004) and LLV with more X4 variants (P = 0.02). CONCLUSION: In individuals with monotypic LLV sequences, higher levels of pre-ART HIV DNA and RNA, systemic inflammation and X4 viruses suggest an interaction between inflammation and the production of virions from proliferating infected cells, and that naïve T cells may be a source of LLV.