Liver fibrosis progression in a cohort of young HIV and HIV/ HBV co-infected patients: A longitudinal study using non-invasive APRI and Fib-4 scores.

Background: The risk of liver fibrosis increases over time in HIV and HIV-HBV individuals even under antiretroviral treatment (ART), warranting a rigorous and periodic monitorization. Given the lower availability of transient elastography, we aimed to assess the longitudinal variation of two non-invasive liver fibrosis scores, APRI and Fib-4, in cases with HIV monoinfection, HIV-HBV co-infection and individuals with HBsAg-seroclearance. Methods: We performed an observational retrospective study between 2013 and 2019 on 212 HIV patients including 111 individuals with HIV mono-infection, 62 individuals with HIV-HBV co-infection and positive HBsAg and 39 cases with HIV-HBV infection and HBsAg-loss. The groups were followed at 36, 48, and 60 months. Liver fibrosis was indicated by an APRI >0.5 or Fib-4≥1.45 score and advanced fibrosis by an APRI score >1.5 or Fib-4 >3.25. Logistic regression with generalized estimating equations (GEE) was used to assess the predictors for the presence of liver fibrosis over time. Results: During a median follow-up of 58.5 months the prevalence of liver fibrosis in all patients increased with 0.5% reaching 11.3% using an APRI score and with 0.9% reaching 10.8% using the Fib-4 score. At the visit corresponding to 60 months the prevalence of liver fibrosis was higher in all HIV-HBV patients compared with individuals with HIV mono-infection, namely: 16.1% on APRI and 12.9% on the Fib-4 score in HIV-HBV/HBsAg-positive individuals, 12.8% on both APRI and Fib-4 scores in HIV-HBV/HBsAg-negative individuals vs. 8.1 and 9%, respectively in HIV mono-infection. The presence of liver fibrosis over the study period was independently associated with plasma HIV RNA, CD4+T cell counts, HIV-HBV co-infection (for APRI >0.5) and ART non-adherence (for Fib-4 >1.45). At the final visit, non-adherence to ART and CD4+T cell counts remained associated with liver fibrosis. Conclusions: The study found a slow progression of APRI and Fib-4 scores over time in young PLWH with extensive ART. Liver fibrosis scores continued to increase in patients with HIV mono-infection yet remained lower than in HIV-HBV patients irrespective on the presence of HBsAg. The periodic follow-up using non-invasive scores on the long-term could help improve the surveillance in low-income settings and high scores should be followed by additional diagnostic methods.

Body composition in HIV-infected patients receiving highly active antiretroviral therapy.

BACKGROUND: The development of combination antiretroviral therapies (cART) represents a significant advance in the treatment of (human immunodeficiency virus) HIV infection. However, several studies report that a large percentage of individuals with HIV, particularly those receiving cART, present body composition differences compared with the general population. The aim of this study was to explore body composition differences by dual-energy X-ray absorptiometry (DEXA), among HIV-positive patients receiving cART, in comparison to healthy controls. METHODS: The cross-sectional study included 60 HIV-infected patients (all under 50 years old). We analyzed the association of antiretroviral medication use and different HIV-related factors, to the body composition parameters. RESULTS: Our cohort had significantly lower fat mass and lower bone mass compared to non HIV-infected persons. Median time since HIV infection diagnosis was 5 years (interquartile range, [IQR], 2-10.25) and viral suppression was achieved in 49 (81.66%) patients. Treatment with protease inhibitors (PIs) was strongly correlated with low fat mass, reduced lean mass and loss of bone mineral density. Nucleoside reverse transcriptase inhibitors (NRTIs)-containing treatment was associated with decrease of lean tissue mass (LM). The prevalence of osteopenia was 41.67% at the lumbar spine (L1-L4) and 36.7% at the hip. We found osteoporosis in 10% of the patients at the lumbar spine. Reduced bone mass was associated, in the patient group, with the duration of PIs use and with smoking (in the males group). CONCLUSION: In our research, HIV-infected individuals compared to healthy controls had body composition differences, including fat mass atrophy and reduced bone mineral content.

Birth outcome in HIV vertically-exposed children in two Romanian centers.

BACKGROUND: The Romanian HIV epidemic is characterized by a high prevalence among children born in the late '80s, perinatally infected. The impact of long-term treatment on their offspring is unknown. We evaluated the influence of prenatal care on the rate of premature birth among the HIV-exposed children of heavily treated HIV-infected mothers in two Romanian centers. METHODS: We retrospectively analyzed data on all patients born by HIV-infected mothers between 2006 and 2012 followed up in two main regional centers. We compared the rate of premature birth and the differences between the sites regarding children and maternal demographic characteristics and antiretroviral exposure in pregnant women. RESULTS: A total of 358 children born to 315 women were enrolled between 2006-2012, 262 children from the National Institute for Infectious Diseases "Prof. Dr. Matei Bals" Bucharest (NIID) and 96 children from the Clinical Infectious Diseases Hospital Constanta (IDHC). Gender rate in newborns and mean age in mothers were similar. We recorded statistically significant differences between centers in the rate of HIV vertical transmission (16.8% vs. 6.2%, p=0.002) and prematurity (25.2 vs. 14.6%, p=0.023). The most used antiretroviral combination during pregnancy in IDHC was boosted lopinavir and fixed dose zidovudine-lamivudine (66% of cases), while in NIID a greater diversity of antiretrovirals were used. Women from IDHC were more frequently treated during pregnancy (83.3% vs. 68.6%, p=0.004). HCV coinfection and illegal drug use were associated with prematurity in the NIID cohort (p=0.037, p=0.024). CONCLUSION: We found a higher rate of premature birth and HIV infection in NIID. In IDHC we found a higher rate of low birth weight in children and a higher rate of heavily treated women. Prematurity was associated with hepatitis C infection and illegal drug use in the NIID cohort.

Severe birth defects in children perinatal exposed to HIV from a "real-world" setting: Infectious Diseases National Institute, Bucharest, Romania.

INTRODUCTION: The shift in epidemic trends in recent years in Romania shows new problems in regard of HIV vertical transmission, firstly in intravenous drug user's mothers co-infected with hepatitis viruses and with social problems, and secondly the children of young mothers with an old HIV infection and long antiretroviral therapy history. MATERIALS AND METHODS: We studied all HIV perinatal exposed children routinely followed up in the Paediatric Department of the National Institute of Infectious Diseases, since January 1st 2006 till December 31st 2012. The analyses consisted of describing the birth defects and association with certain risk factors: gender, mother's age at birth and exposure to antiretrovirals in the first trimester of pregnancy. RESULTS: We analyzed 244 children born to HIV-infected mothers. The incidence of HIV infection was 16.39%. The rate of birth defects was 39.34% (96/244 cases). The most frequent findings were cardiac malformations (47/96), followed by musculoskeletal defects (24/96), neurologic defects (20/96), urogenital malformations (13/96), digestive tract defects (3/93), metabolic disorders (2/96) and genetic disorders (2/96). We found nine cases of severe congenital anomalies: complex heart defect, total congenital aganglionic megacolon, anal imperforation, Dandy-Walker syndrome, gangliosidosis, Niemann-Pick syndrome, Down syndrome, true hermaphroditism and cleft palate. Two children died during first year of life due to severe malformations. 9% of cases had associated malformations. The gender rate was in favour of males in group with birth defects (58/38) and with no birth defects (82/66). The median age at birth in mothers was 22 years, similar in both groups. The highest mean age at birth was in offspring's mothers with neurologic congenital defects 25, 15 years old, but is not statistically significant (p=0.1). In the studied period the highest number of birth defects were found in 2012, 37 children, compared with less than 15 in previous years (not statistically significant, p=0.07). In our studied patients the risk of birth defects was not statistically associated with HIV transmission or with exposure to antiretrovirals before and in first trimester of pregnancy (p=0.88). CONCLUSION: The rate of birth defects among HIV-exposed children was not significantly associated with antiretroviral exposure, but we identify very rare and severe congenital conditions. We have noticed also a trend to increasing number of birth defects in 2012 among studied patients compared to previous years.

ART management in children perinatally infected with HIV from mothers who experience behavioural changes in Romania.

INTRODUCTION: During the recent years the rate of HIV perinatally exposed children in Romania has increased as a consequence of the expanding number of HIV-infected women. These women belong to Romania's long-terms survivors, aged between 20 and 24 years and to the group of new HIV infection cases (20-24 years), acquired through unsafe sexual contact and use of new psychoactive substance (IV). MATERIALS AND METHODS: We focused on 396 HIV perinatally exposed children born between 2008 and 2013, under surveillance in National Institute for Infectious Diseases "Prof. Dr. Matei Bals," Bucharest. Of them, 43 acquired HIV through materno-foetal transmission. Our aim was to observe the characteristics in their evolution under antiretroviral treatment and to emphasize the causes of treatment failure. Children with perinatally acquired HIV infection were followed in a retrospective case series. We assessed maternal characteristics, HIV vertical transmission prophylaxis, timing of diagnosis, immunological and virologic status and features of the evolution under combined antiretroviral therapy (cART). RESULTS: The rate of mother-to-child HIV transmission was 10.8% versus the national rate registered in 2013, namely <5%. 16% of mothers belonged to the Romanian 1990s cohort and 84% were recently infected with HIV, through unprotected sexual contact (70%) or use of new psychoactive substances (14%). 51% of mothers were diagnosed postnatally as a consequence of their reluctance to access specific health services and in 57% CD4 value was <350 cell/mm. 41% of the monitored children were diagnosed with HIV infection at birth. Their median entry CD4 value was 23% and 49% had a CD4 >25%; median entry viral load was 7 log. 16 patients (37%) had undetectable viral load after six months of treatment. In 87.5% of them the virologic suppression was achieved and maintained with one single regimen (2 NRTIs+1 NNRTI or 2 NRTIs+1 PI/r). 15 children (35%) did not achieve suppression of viral load. 19 children (44%) faced special issues related to adherence to antiretroviral treatment, due to mothers' poor adherence to a basic set of cares destined for their children. CONCLUSIONS: Prevention programmes in Romania must be designed on the basis of the new economic context and emerging psychoactive substance use. Hence, women who use drugs should benefit from a wider access to medical and social services.

Serum adipokines and HIV viral replication in patients undergoing antiretroviral therapy.

INTRODUCTION: Several studies have reported that cytokines secreted by adipose tissue (adipokines) may be linked to HIV replication. The aim of the study was to evaluate the relationship between HIV replication and serum levels of adipokines, in a Caucasian HIV-infected population of men and women undergoing complex antiretroviral therapy. METHODS: A cross-sectional study was conducted in an unselected sample of 77 HIV-1-positive patients. Serum adipokines levels were measured including circulating adiponectin, leptin, resistin, tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Patients were divided into two groups: Group 1 - with undetectable viral load and Group 2 - with persistent HIV viral replication. Differences between groups ? were tested using independent-sample t-test for Gaussian variables and Mann-Whitney-Wilcoxon test for non-parametric variables. Pearson's chi-squared test was used for correlation analysis. RESULTS: A total of 77 patients (age range: 17-65, mean: 32.5 years) including 44 men (57.1% men, age range: 17-63 years, mean: 34.1 years) and 33 women (42.9% women age range: 19-65 years, mean: 30.3 years) were included in the study. TNF-alpha had significantly higher serum levels in patients with detectable viral load (16.89 vs. 9.35 pg/mL), (p=0.043), but correlation analysis lacked statistical significance. Adiponectin had median serum levels of 9.22 ìg/mL in Group 1 vs. 16.50 ìg/mL in Group 2 but the results lacked statistical significance (p=0.059). Higher leptin, IL-6 and resistin serum levels were noted in patients with undetectable HIV viral load, without statistical significance. CONCLUSIONS: The present study reported higher TNF-alpha serum levels in patients with persistent HIV viral load. We found no statistically significant correlations between adiponectin, leptin, resistin and IL-6 and HIV viral load in our Caucasian HIV-positive study population, undergoing antiretroviral therapy.