Effect of Two Forms of Tenofovir on Duodenal Enterocytes - a Hypothesis for Different Effect of TDF and TAF on Body Weight and Plasma Lipids.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) compared to tenofovir alafenamide (TAF) leads to lower body weight and plasma lipids by an unknown mechanism. We hypothesize that TDF, when absorbed, may damage enterocytes of the proximal duodenum, leading to reduced absorption of nutrients. METHODS: People living with HIV, without significant gastrointestinal symptoms, receiving TDF (n=12) or TAF (n=12) containing regimen underwent esophagogastroduodenoscopies with duodenal biopsies. Plasma/serum concentrations of nutrients absorbed from proximal duodenum and serum intestinal fatty-acid-binding protein (I-FABP), a marker of enterocyte damage, were measured. COX/SDH histochemical staining and electron microscopy (EM) were conducted to evaluate mitochondria. RESULTS: Five patients in TDF (celiac disease (excluded from further analyses), helicobacter gastritis, and three esophagitis) and two in TAF group (two esophagitis) had a pathological finding in esophagogastroduodenoscopy. Villi were flatter (337 (59) vs. 397 (42) µm, p=0.016), crypts non-significantly deeper (200 (46) vs. 176 (27) µm, p=0.2), and villus to crypt ratio lower (1.5 (0.42) vs. 2.5 (0.51), p=0.009) in TDF vs. TAF group. I-FABP concentration was higher in TDF vs. TAF group (3.0 (1.07) vs. 1.8 (0.53) ng/ml, p=0.003). TDF group had numerically but not statistically significantly lower concentrations of folate, vitamins A, B1, D, and E. COX/SDH staining showed signs of mitochondrial damage in 10 participants in TDF and 11 in TAF group. EM studies showed similar mitochondrial damage in both groups. CONCLUSIONS: Duodenal villous alterations may explain TDF-associated decrease in body weight and plasma lipids. Larger studies are needed to evaluate concentrations of nutrients absorbed from duodenum among TDF users.

Induced abortions of women living with HIV in Finland 1987-2019: a national register study.

BACKGROUND: Recent data on the rate and risk factors of induced abortion among women living with HIV (WLWH) are limited. Our aim was to use Finnish national health register data to 1) determine the nationwide rate of induced abortions of WLWH in Finland during 1987-2019, 2) compare the rates of induced abortions before and after HIV diagnosis over different time periods, 3) determine the factors associated with terminating a pregnancy after HIV diagnosis, and 4) estimate the prevalence of undiagnosed HIV at induced abortions to see whether routine testing should be implemented. METHODS: A retrospective nationwide register study of all WLWH in Finland 1987-2019 (n = 1017). Data from several registers were combined to identify all induced abortions and deliveries of WLWH before and after HIV diagnosis. Factors associated with terminating a pregnancy were assessed with predictive multivariable logistic regression models. The prevalence of undiagnosed HIV at induced abortion was estimated by comparing the induced abortions among WLWH before HIV diagnosis to the number of induced abortions in Finland. RESULTS: Rate of induced abortions among WLWH decreased from 42.8 to 14.7 abortions/1000 follow-up years from 1987-1997 to 2009-2019, more prominently in abortions after HIV diagnosis. After 1997 being diagnosed with HIV was not associated with an increased risk of terminating a pregnancy. Factors associated with induced abortion in pregnancies that began after HIV diagnosis 1998-2019 were being foreign-born (OR 3.09, 95% CI 1.55-6.19), younger age (OR 0.95 per year, 95% CI 0.90-1.00), previous induced abortions (OR 3.36, 95% CI 1.80-6.28), and previous deliveries (OR 2.13, 95% CI 1.08-4.21). Estimated prevalence of undiagnosed HIV at induced abortion was 0.008-0.029%. CONCLUSIONS: Rate of induced abortions among WLWH has decreased. Family planning should be discussed at every follow-up appointment. Routine testing of HIV at all induced abortions is not cost-effective in Finland due to low prevalence.

Psychosocial health in pregnancy and postpartum among women living with - and without HIV and non-pregnant women living with HIV living in the Nordic countries - Results from a longitudinal survey study.

BACKGROUND: The success of antiretroviral therapy has normalized pregnancy among women living with HIV (WWH) with a very low risk of perinatal transmission of HIV. Despite these advances, WWH still face complex medical and psychosocial issues during pregnancy and postpartum. The aim of this study was to assess differences in psychosocial health outcomes between pregnant WWH, non-pregnant WWH, and pregnant women without HIV, and further identify factors associated with probable depression in the third trimester and postpartum. METHODS: In a longitudinal survey study, participants were included from sites in Denmark, Finland, and Sweden during 2019-2020. Data was collected in the 3rd trimester, 3 and 6 months postpartum using standardized questionnaires assessing depression, perceived stress, loneliness, and social support. Mixed regression models were used to assess changes over time within and between groups. Logistic regression models were used to identify factors associated with depression in pregnancy and postpartum. RESULTS: A total of 47 pregnant WWH, 75 non-pregnant WWH, and 147 pregnant women without HIV were included. The prevalence of depression was high among both pregnant and non-pregnant WWH. There was no significant difference between pregnant and non-pregnant WWH in depression scores, perceived stress scores, or social support scores at any time point. Compared to pregnant women without HIV, pregnant WWH reported worse outcomes on all psychosocial scales. Social support and loneliness were associated with an increased odds of depressive symptoms in the adjusted analysis. CONCLUSIONS: A high burden of adverse psychosocial outcomes was observed in both pregnant and non-pregnant women living with HIV compared to pregnant women without HIV. Loneliness and inadequate social support were associated with increased odds of depression in pregnancy and should be a focus in future support interventions.

Clinical Outcomes in Persons Coinfected With Human Immunodeficiency Virus and Hepatitis C Virus: Impact of Hepatitis C Virus Treatment.

BACKGROUND: A hepatitis C (HCV) cure is associated with changes in lipids and inflammatory biomarkers, but its impact on clinical endpoints among treated human immunodeficiency virus (HIV)/HCV coinfected persons is unclear. METHODS: People living with HIV from EuroSIDA with a known HCV status after January 2001 were classified into strata based on time-updated HCV RNA measurements and HCV treatment, as either HCV antibody-negative; spontaneously resolved HCV; chronic, untreated HCV; cured HCV (HCV RNA-negative); or HCV treatment failures (HCV RNA-positive). Poisson regression was used to compare incidence rates between HCV groups for end-stage liver disease (ESLD; including hepatocellular carcinoma [HCC]), non-acquired immunodeficiency virus defining malignancy (NADM; excluding HCC), and cardiovascular disease (CVD). RESULTS: There were 16 618 persons included (median follow-up 8.3 years, interquartile range 3.1-13.7). There were 887 CVD, 902 NADM, and 436 ESLD events; crude incidence rates/1000 person-years follow-up were 6.4 (95% confidence interval [CI] 6.0-6.9) for CVD, 6.5 (95% CI 6.1-6.9) for NADM, and 3.1 (95% CI 2.8-3.4) for ESLD. After adjustment, there were no differences in incidence rates of NADM or CVD across the 5 groups. HCV-negative individuals (adjusted incidence rate ratio [aIRR] 0.22, 95% CI 0.14-0.34) and those with spontaneous clearance (aIRR 0.61, 95% CI 0.36-1.02) had reduced rates of ESLD compared to cured individuals. Persons with chronic, untreated HCV infections (aIRR 1.47, 95% CI 1.02-2.13) or treatment failure (aIRR 1.80, 95% CI 1.22-2.66) had significantly raised rates of ESLD, compared to those who were cured. CONCLUSIONS: Incidences of NADM or CVD were independent of HCV group, whereas those cured had substantially lower incidences of ESLD, underlining the importance of successful HCV treatment for reducing ESLD.

Declining prevalence of cytological squamous intraepithelial lesions of the cervix among women living with well-controlled HIV - Most women living with HIV do not need annual PAP smear screening.

INTRODUCTION: Cervical screening by means of annual Papanicolaou (PAP) smears has been recommended for all women living with HIV. We analysed the results of our annual PAP smear screening program to identify low-risk subgroups for less rigorous screening. MATERIAL AND METHODS: The study comprised 369 women followed at the Helsinki University Hospital 2002-2013, with a total of 2033 PAP smear results. We analyzed the temporal changes in PAP smear findings. Logistic regression analysis for binominal dependent variables was used for assessing risk factors for ever having cytological squamous intraepithelial lesions (hereafter referred as SIL) using generalized estimating equations taking into account multiple observations of each patient. RESULTS: Most women had well-controlled HIV, especially towards the end of the study. PAP smear results improved substantially. At the time of each individual's last PAP smear, 90.0% of the findings displayed normal results. Conversely, the rate of SIL decreased from 16.8% to 4.6% from 2002 to 2013. In multivariate analysis the risk of SIL was significantly lower in women with consecutive normal PAP smear findings during the first two years of follow up [odds ratio (OR) 0.21, 95% confidence interval (CI) 0.10-0.45, p < 0.001] and with CD4 counts >500 cells/µL (OR 0.11, 95% CI 0.05-0.26, p < 0.001). CONCLUSIONS: Widespread use of combination antiretroviral therapy (cART) and systematic cervical screening has reduced the rate of abnormal PAP smears. It seems feasible to identify low-risk women by combining HIV-related information and PAP smear results. Screening low-risk women living with HIV at three-year intervals similar to HIV-negative women appears justified.

Perception and Emotional Experiences of Infant Feeding Among Women Living With HIV in a High-Income Setting: A Longitudinal Mixed Methods Study.

BACKGROUND: The recommendation of breastfeeding avoidance for women living with HIV in high-income settings may be influenced by cultural beliefs and come at an emotional cost. This multicenter, longitudinal, convergent mixed methods study aimed to compare differences in attitudes, concerns, and experiences surrounding breastfeeding in women living with HIV of Nordic and non-Nordic origin. SETTING: High-income setting. METHODS: Pregnant women living with HIV in the Nordic countries Denmark, Finland, and Sweden were recruited in 2019-2020. Quantitative data on attitudes surrounding infant feeding were assessed using the Positive Attitudes Concerning Infant Feeding questionnaire completed in the third trimester (T1), and 3 (T2) and 6 (T3) months postpartum. Women who completed the survey were also invited to participate in semistructured interviews at T1 and T3. The findings from the quantitative survey and qualitative interviews were brought together through merging to assess for concordance, complementarity, expansion, or discordance between the data sets and to draw metainferences. RESULTS: In total, 44 women completed the survey, of whom 31 also participated in qualitative interviews. The merged analyses identified three overarching domains representing commonalities across the quantitative and qualitative data: emotional impact, justifying not breastfeeding, and coping strategies. Not being able to breastfeed was emotionally challenging. Cultural expectations influenced the women's experiences and the strategies they used to justify their infant feeding choice. CONCLUSIONS: For women living with HIV in Nordic countries not breastfeeding was a complex, multilayered process substantially influenced by social and cultural expectations.

Infant feeding knowledge among women living with HIV and their interaction with healthcare providers in a high-income setting: a longitudinal mixed methods study.

BACKGROUND: Recent changes in the infant feeding guidelines for women living with HIV from high-income countries recommend a more supportive approach focusing on shared decision-making. Limited information is available on the infant feeding knowledge of women living with HIV and how healthcare providers engage with them in this context. This multicenter, longitudinal, mixed methods study aims to get a comprehensive and nuanced understanding of infant feeding knowledge among women living with HIV of Nordic and non-Nordic origin living in Nordic countries, and their interaction with healthcare providers regarding infant feeding planning. METHODS: Pregnant women living with HIV in Denmark, Finland, and Sweden were recruited in 2019-2020. The Positive Attitudes Concerning Infant Feeding (PACIFY) questionnaire was completed in the 3rd trimester (T1), three (T2), and six (T3) months postpartum. Women who completed the quantitative survey were also invited to participate in qualitative semi-structured interviews at T1 and T3. Results from the survey and interviews were brought together through merging to assess for concordance, complementarity, expansion, or discordance between the datasets and to draw meta-inferences. RESULTS: In total, 44 women living with HIV completed the survey, of whom 31 also participated in the interviews. The merged analyses identified two overarching domains: Knowledge about breastfeeding in the U = U era and Communications with healthcare providers. The women expressed confusion about breastfeeding in the context of undetectable equals untransmittable (U = U). Women of Nordic origin were more unsure about whether breastfeeding was possible in the context of U = U than women of non-Nordic origin. Increased postpartum monitoring with monthly testing of the mother was not seen as a barrier to breastfeeding, but concerns were found regarding infant testing and infant ART exposure. Infant feeding discussions with healthcare providers were welcome but could also question whether breastfeeding was feasible, and many participants highlighted a need for more information. CONCLUSIONS: Healthcare providers caring for women living with HIV must have up-to-date knowledge of HIV transmission risks during breastfeeding and engage in shared decision-making to optimally support infant feeding choices.

Switching from tenofovir alafenamide to tenofovir disoproxil fumarate improves lipid profile and protects from weight gain.

BACKGROUND: Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) increases low-density lipoprotein cholesterol (LDL-C) and body weight. Metabolic effects of the opposite TAF-to-TDF switch are unknown. OBJECTIVES: To investigate the effect of TAF-to-TDF switch on plasma lipids, body weight, and atherosclerotic cardiovascular disease (ASCVD) risk score. DESIGN: A retrospective chart review. METHODS: One hundred and forty-six patients with TAF-to-TDF switch (Switch group) were compared with 146 patients matched for sex, age, and third antiretroviral agent class who continued unchanged TAF-containing regimen (Control group). Data were collected at approximately 1 year (follow-up FU-1) and 2 years (follow-up FU-2) after baseline values. RESULTS: In Switch group at FU-1, total cholesterol (TC) and LDL-C decreased 12.1% and 12.4% ( P  < 0.001 in both), respectively. High-density lipoprotein cholesterol (HDL-C) also decreased 8.2% ( P  < 0.001) in Switch group, but TC/HDL-C ratio did not change. No statistically significant changes were observed in Control group in any lipid values. TC remained similarly decreased through FU-2 in Switch group, but LDL-C increased from FU-1 to FU-2 in both groups. ASCVD risk score decreased from 6.3% at baseline to 6.0% at FU-2 ( P  = 0.012) in Switch group but increased from 8.4 to 9.1% ( P  = 0.162) in Control group. Body weight increased from 83.4 kg at baseline to 84.9 kg at FU-2 ( P  = 0.025) in Control group but remained stable in Switch group (83.1-83.7 kg, P  = 0.978). CONCLUSIONS: TAF-to-TDF switch improved plasma lipid profile and ASCVD risk score, as well as prevented weight gain, when compared with ongoing TAF-based antiretroviral therapy.

Finnish HIV Quality of Care Register (FINHIV).

PURPOSE: The Finnish HIV Quality of Care Register (FINHIV) was created to: (1) estimate the number of people living with HIV (PLWH) in Finland, (2) evaluate the national level of antiretroviral medication use and viral suppression, (3) examine the change in the HIV epidemic in Finland to pinpoint issues to address and (4) enable evaluation of the health of the PLWH by combining the FINHIV data with other national healthcare data. PARTICIPANTS: The FINHIV includes all people diagnosed or being treated for HIV infection in Finland since 1984. The register was formed in 2020 by combining data from the National Infectious Diseases Register (information from time of diagnosis, data from 1984) and from the 21 HIV Clinics that treat HIV-positive patients in Finland (earliest data from 1998). The register population forms a nationwide, open cohort with yearly updates; currently it consists of 4218 PLWH (including 718 deceased) with HIV diagnosed or treated in Finland 1984-2019. Current rate of new cases is 150 cases/year. FINDINGS TO DATE: From the FINHIV data, we can confirm that Finland has reached the Joint United Nations Programme for HIV/AIDS (UNAIDS) 90-90-90 targets set for 2020, and that the proportion of virally suppressed is constant between all 21 HIV Clinics in Finland, despite their varying size. Linkage to care is estimated at 94.3% of those diagnosed. In contrast to the treatment results, more than half of the PLWH have been diagnosed at a late stage, and the proportion has increased since 2000. FUTURE PLANS: Combinations of FINHIV data with other national healthcare register data in Finland will provide further information on other aspects of the health of the PLWH in a high-resource setting (eg, comorbidities, sexual health and use of healthcare resources). Additionally, implementation of patient-reported experience and outcome measures within the FINHIV is ongoing.

The experience of pregnancy among women living with HIV in Nordic countries: A qualitative narrative enquiry.

OBJECTIVE: The success of antiretroviral therapy has resulted in the normalization of pregnancy among women living with HIV and a very low risk of perinatal transmission of HIV. Despite these advances, women living with HIV still face complex medical and psychosocial issues during pregnancy. The purpose of this study is to describe experiences of pregnancy and the relevance of social support among women living with HIV in Nordic countries. METHODS: This qualitative study examined data from pregnant women living with HIV from sites in Denmark, Sweden and Finland from 2019 to 2020. Data were collected in the third trimester via individual interviews using a hybrid, narrative/semistructured format. The transcribed interviews were analyzed using narrative thematic analysis. RESULTS: In total, 31 women living with HIV were enrolled, of whom 61% originated from an African country and 29% from a Nordic country. The analysis generated four primary narrative themes: just a normal pregnancy, unique considerations and concerns, interactions with healthcare, and social support. Women living with HIV have a strong desire to have normal pregnancies and to be treated like any other pregnant woman. However, this normality is fragile, and being pregnant and living with HIV does come with unique considerations and concerns, such as fear of transmission, antiretroviral therapy, and the need for specialized care, which are fundamental to the women's experiences. Interactions with healthcare providers and social support influence their experiences in both positive and negative ways. CONCLUSION: The findings emphasize a sense of normality in pregnancy among women living with HIV. However, pregnancy does come with unique considerations and concerns, which highly influence the women's experience of pregnancy. Healthcare providers should focus on person-centered care, ensuring continuity and that women living with HIV do not feel discriminated against throughout their pregnancy.

The levonorgestrel-releasing intrauterine system in human immunodeficiency virus-infected women: a 5-year follow-up study.

OBJECTIVE: We sought to assess the effects of long-term use and safety of the levonorgestrel-releasing (LNG)-intrauterine system (IUS) among human immunodeficiency virus (HIV)-infected women in comparison with HIV-infected women not using the device. STUDY DESIGN: Fifteen women using the LNG-IUS and their 25 age- and CD4(+) lymphocyte count-matched control subjects with annual follow-up data were followed up for 5 years. RESULTS: No unplanned pregnancies or pelvic infections occurred among the LNG-IUS users. Altogether, 12 (80%) of the LNG-IUS users continued its use up to 5 years. Annual CD4(+) lymphocyte counts were similar in the LNG-IUS users and control subjects throughout the follow-up period. The hemoglobin levels increased initially (P < .005) and remained higher among the LNG-IUS users (P < .02). Pap smears displayed non-squamous intraepithelial lesion cytology in ≥ 85% of cases in both groups. CONCLUSION: No unfavorable effects on the course of HIV infection were noted during long-term use of the LNG-IUS. Dual protection by means of an LNG-IUS and condoms might be an ideal contraceptive strategy for HIV-infected women.

Effectiveness and Safety of Interferon-Free Direct-Acting Antiviral Hepatitis C Virus Therapy in HIV/Hepatitis C Virus Coinfected Individuals: Results From a Pan-European Study.

OBJECTIVES: To investigate the effectiveness, safety, and reasons for premature discontinuation of direct-acting antivirals (DAAs) in a diverse population of HIV/hepatitis C virus (HCV) coinfected individuals in Europe. METHODS: All HIV/HCV coinfected individuals in the EuroSIDA study that started interferon free DAA treatment between January 6, 2014, and January 3, 2018, with ≥12 weeks of follow-up after treatment stop were included in this analysis. Sustained virological response (SVR) was defined as a negative HCV-RNA result ≥12 weeks after stopping treatment (SVR12). Logistic regression was used to explore factors associated with SVR12. RESULTS: 1042 individuals started interferon-free DAA treatment after 1/6/2014 and were included, 862 (82.2%) had a known response to treatment, and 789 [91.5%, 95% confidence interval (CI): 89.7 to 93.4] of which achieved SVR12. There were no differences in SVR12 across regions of Europe (P = 0.84). After adjustment, the odds of achieving SVR12 was lower in individuals that received sofosbuvir/simeprevir ± ribavirin (RBV) [adjusted odds ratio 0.21 (95% CI: 0.08 to 0.53)] or ombitasvir/paritaprevir/dasabuvir ± RBV [adjusted odds ratio 0.46 (95% CI: 0.22 to 1.00)] compared with sofosbuvir/ledipasvir ± RBV. Forty-three (4.6%) individuals had one or more components of their HCV regimen stopped early, most commonly because of toxicity (n = 14); of these 14, 11 were treated with ribavirin. Increased bilirubin was the most common grade 3 or 4 laboratory adverse event (n = 15.3%) and was related to treatment with atazanavir and ribavirin. CONCLUSIONS: Our findings from real-world data on HIV/HCV coinfected individuals across Europe show DAA treatment is well tolerated and that high rates of SVR12 can be achieved in all regions of Europe.

Influence of hepatitis C virus co-infection and hepatitis C virus treatment on risk of chronic kidney disease in HIV-positive persons.

BACKGROUND: Hepatitis C virus (HCV) infection has been associated with increased risk of chronic kidney disease (CKD). We investigated the impact of HCV cure on CKD in HIV-positive persons in the EuroSIDA study. METHODS: HIV-positive persons with known HCV status and at least three serum creatinine measurements after 1/1/2004 were compared based on time-updated HCV-RNA and HCV treatment: anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, and HCV-RNA positive after HCV treatment. Poisson regression compared incidence rates of CKD [confirmed (>3 months apart) eGFR <60 ml/min per 1.73 m] between HCV strata. RESULTS: Fourteen thousand, seven hundred and fifty-four persons were included; at baseline 9273 (62.9%) were HCV-Ab negative, 696 (4.7%) spontaneous clearers, 3021 (20.5%) chronically infected, 922 (6.2%) successfully treated and 842 (5.7%) HCV-RNA positive after treatment. During 115 335 person-years of follow-up (PYFU), 1128 (7.6%) developed CKD; crude incidence 9.8/1000 PYFU (95% CI 9.2-10.4). After adjustment, persons anti-HCV negative [adjusted incidence rate ratio (aIRR) 0.59; 95% CI 0.46-0.75] and spontaneous clearers (aIRR 0.67; 95% CI 0.47-0.97) had significantly lower rates of CKD compared with those cured whereas persons chronically infected (aIRR 0.85; 95% CI 0.65-1.12) and HCV-RNA positive after treatment (aIRR 0.71; 95% CI 0.49-1.04) had similar rates. Analysis in those without F3/F4 liver fibrosis using a more rigorous definition of CKD showed similar results. CONCLUSION: This large study found no evidence that successful HCV treatment reduced CKD incidence. Confounding by indication, where those with highest risk of CKD were prioritized for HCV treatment in the DAA era, may contribute to these findings.

Influence of Hepatitis C Coinfection and Treatment on Risk of Diabetes Mellitus in HIV-Positive Persons.

BACKGROUND: The role of hepatitis C virus (HCV) coinfection and HCV-RNA in the development of diabetes mellitus (DM) in HIV-positive persons remains unclear. METHODS: Poisson regression was used to compare incidence rates of DM (blood glucose >11.1 mmol/L, HbA1C >6.5% or >48 mmol/mol, starting antidiabetic medicine or physician reported date of DM onset) between current HIV/HCV groups (anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, HCV-RNA-positive after HCV treatment). RESULTS: A total of 16 099 persons were included; at baseline 10 091 (62.7%) were HCV-Ab-negative, 722 (4.5%) were spontaneous clearers, 3614 (22.4%) were chronically infected, 912 (5.7%) had been successfully treated, and 760 (4.7%) were HCV-RNA-positive after treatment. During 136 084 person-years of follow-up (PYFU; median [interquartile range], 6.9 [3.6-13.2]), 1108 (6.9%) developed DM (crude incidence rate, 8.1/1000 PYFU; 95% CI, 7.7-8.6). After adjustment, there was no difference between the 5 HCV strata in incidence of DM (global P = .33). Hypertension (22.2%; 95% CI, 17.5%-26.2%) and body mass index >25 (22.0%; 95% CI, 10.4%-29.7%) had the largest population-attributable fractions for DM. CONCLUSIONS: HCV coinfection and HCV cure were not associated with DM in this large study. The biggest modifiable risk factors were hypertension and obesity, and continued efforts to manage such comorbidities should be prioritized.

Exposure to dolutegravir in pregnant women living with HIV in Central and Eastern Europe and neighboring countries - data from the ECEE Network Group.

OBJECTIVES: The purpose of this study was to investigate dolutegravir (DTG) use among women and exposure to DTG during pregnancy in real world in Central and Eastern Europe and neighboring countries. MATERIAL AND METHODS: Centres from 20 countries included in the Euroguidelines in Central and Eastern Europe (ECEE) Network and Finland were asked to complete an on-line questionnaire. RESULTS: Seven centres from Czech Republic, Finland, Greece, Poland, Slovakia, and Turkey provided detailed information. DTG exposure was reported in 415 women, of which 26 were during pregnancy. Of those, 22 were on DTG at the time of conception and 4 had started DTG during pregnancy. Few women had conventional risk factors. The data on folic acid usage was unknown for eight women; 14 were using and four were not using folic acid. Four pregnancies were ongoing at the time of the study and of those with an outcome, 77.3% resulted with term, 13.6% preterm delivery, 4.5% spontaneous and 4.5% medical abortion. CONCLUSIONS: The DTG signal report indicates the importance of safety research for drug use in pregnancy and highlights the urgent need for systematic surveillance of pregnancy outcomes and neonatal surveillance. Countries with low- or moderate HIV prevalence should be included in studies reviewing pregnancy outcomes and in any surveillance system to ensure the accuracy of drug safety revision.

Study protocol: becoming and being a mother living with HIV - a multicentre longitudinal mixed methods study among pregnant women living with HIV, non-pregnant women living with HIV and pregnant women not living with HIV in a high-income setting (the 2B MOM study).

INTRODUCTION: The success of combination antiretroviral therapy has decreased the risk of perinatal HIV transmission and normalised pregnancy in women living with HIV (WLWH). Despite these advances, WLWH still face complex medical and psychosocial issues during pregnancy and postpartum, and there is a gap of knowledge on the experiences of becoming and being a mother living with HIV in today's context. The overall aim of this study is to investigate psychosocial outcomes and experiences of WLWH in Scandinavia during pregnancy and early motherhood. METHODS AND ANALYSIS: This is a multicentre longitudinal convergent mixed methods study consisting of a quantitative survey study, a qualitative interview study and a mixed methods analysis. The survey study aims to examine psychosocial outcomes of WLWH across the pregnancy - postpartum trajectory. Participants are pregnant WLWH living in Scandinavia. Two control groups of HIV-negative pregnant women and non-pregnant WLWH are also included. Data is collected in the third trimester, 3 and 6 months postpartum using standardised questionnaires. Statistical analysis will assess changes over time and identify predictors of adverse outcomes. The interview study seeks to understand experiences of pregnancy and becoming a mother while living with HIV. Pregnant WLWH who are enrolled in the survey study will be asked to participate in individual interviews in the third trimester and 6 months postpartum. Data will be analysed using narrative analysis. The survey and interview results will be merged in a mixed methods analysis to assess confirmation, expansion or discordance between the data sets. ETHICS AND DISSEMINATION: Approval from the Danish Data Protection Agency (VD-2018-253), and the Finnish and Swedish Ethics Committees have been obtained (HUS/1330/2019 and Dnr: 2019-04451, respectively). Study results will be disseminated to patient organisations, through publications in peer-reviewed journals and at scientific conferences.

Most women living with HIV can deliver vaginally-National data from Finland 1993-2013.

INTRODUCTION: Vaginal delivery has been recommended for more than ten years for women living with HIV (WLWH) with good virological control. However, in Europe most WLWH still deliver by cesarean section (CS). Our aim was to assess the rate of vaginal delivery and the indications for CS in WLWH over 20 years in a setting of low overall CS rate. MATERIALS AND METHODS: This was a retrospective study of all WLWH delivering in Finland 1993-2013. We identified the women by combining national health registers and extracted data from patient files. RESULTS: The study comprised 212 women with 290 deliveries. Over 35% of the women delivered several children during the study years. During 2000-2013, with consistent viral load monitoring, 80.0% showed HIV viral loads <50 copies/mL in the last measurement preceding the delivery. Altogether 74.5% of all WLWH delivered vaginally and the rate of both elective CS and emergency CS was 12.8% each. For most CSs (63.5%) the indication was obstetrical, for 28.4% it was avoiding HIV transmission and for 0.7% it was mother's request. In hospitals with less than ten HIV-related deliveries during the study period, the rate of elective CS was higher than in more experienced hospitals (22.7% versus 10.6% [p = 0.024]). No perinatal HIV transmissions occurred. CONCLUSIONS: Most WLWH can achieve good virological control and deliver vaginally. This will help them to maintain their future child bearing potential and reduce CS-related morbidity.

Systemic Inflammation, Coagulation, and Clinical Risk in the START Trial.

BACKGROUND: The Strategic Timing of AntiRetroviral Treatment (START) trial demonstrated that immediate (at CD4+ >500 cells/µL) vs deferred (to CD4+ <350 cells/µL or AIDS) antiretroviral therapy (ART) initiation reduced risk for AIDS and serious non-AIDS (SNA). We investigated associations of inflammation, coagulation, and vascular injury biomarkers with AIDS, SNA or death, and the effect of immediate ART initiation. METHODS: Biomarkers were measured from stored plasma prior to randomization and at month 8. Associations of baseline biomarkers with event risk were estimated with Cox regression, pooled across groups, adjusted for age, gender, and treatment group, and stratified by region. Mean changes over 8 months were estimated and compared between the immediate and deferred ART arms using analysis of covariance models, adjusted for levels at entry. RESULTS: Baseline biomarker levels were available for 4299 START participants (92%). Mean follow-up was 3.2 years. Higher levels of IL-6 and D-dimer were the only biomarkers associated with risk for AIDS, SNA or death, as well as the individual components of SNA and AIDS events (HRs ranged 1.37-1.41 per 2-fold higher level), even after adjustment for baseline CD4+ count, HIV RNA level, and other biomarkers. At month 8, biomarker levels were lower in the immediate arm by 12%-21%. CONCLUSIONS: These data, combined with evidence from prior biomarker studies, demonstrate that IL-6 and D-dimer consistently predict clinical risk across a broad spectrum of CD4 counts for those both ART-naïve and treated. Research is needed to identify disease-modifying treatments that target inflammation beyond the effects of ART.

Perception of sexuality and fertility in women living with HIV: a questionnaire study from two Nordic countries.

INTRODUCTION: As the human immunodeficiency virus (HIV)-positive population ages, issues concerning sexuality and fertility, among others, are becoming relevant. HIV is still surrounded by stigma and taboos, and there have been few studies conducted in industrialized settings concerning these questions. We therefore wanted to investigate the perception of sexuality and fertility in women living with HIV (WLWH) in an industrialized setting, using a questionnaire. METHODS: WLWH were recruited at their regular outpatient clinic visits, at the major Departments of Infectious Diseases in Denmark and Finland, from January 2012 to October 2013. A questionnaire was developed, study participants were informed of the nature of study and, if they agreed to participate and signed a consent form, they filled in the questionnaire. Demographic information on the participants was obtained from patient files (in Finland) or from a national HIV cohort (in Denmark). Statistical analysis was performed using STATA, version 11. RESULTS: In total, 560 women were included in the study. The median age was 44 years. The majority were of white European origin, with fully suppressed HIV viral load, CD4 cell count >350 µL and mild or no symptoms of their HIV infection. A total of 62% were sexually active, stating condom use as their sole form of contraception. Of the sexually inactive women, one-third were in steady relationships. Eighty percent reported prior pregnancies, of which the majority had one or more children. Most children were born prior to the women's HIV diagnosis and the mode of conception was predominantly natural. One-quarter of the participating women desired pregnancy, while more than half did not. The remaining quarter either stated that they already had the desired number of children or chose not to answer the question. Fourteen percent stated that their HIV diagnosis ended their wish for children; of these women, the median time of diagnosis was between 1995 and 1996. Pregnancy had been attempted unsuccessfully in one-quarter of study participants. The final question inquired what the risk of mother-to-child transmission was, with all precautions taken. Fifteen percent estimated the risk to be above two percent. CONCLUSIONS: In conclusion, the majority of WLWH in industrialized settings in Denmark and Finland have few HIV-related symptoms, are sexually active and have a strong desire for children.