Rilpivirine in HIV-1-positive women initiating pregnancy: to switch or not to switch?

2020 ◽  
Vol 75 (5) ◽  
pp. 1324-1331
Author(s):  
Pierre Frange ◽  
Roland Tubiana ◽  
Jeanne Sibiude ◽  
Ana Canestri ◽  
Cédric Arvieux ◽  
...  
Keyword(s):  
Pregnancy Outcomes ◽  
Viral Suppression ◽  
Hiv Transmission ◽  
Plasma Concentrations ◽  
Safety Data ◽  
Viral Rebound ◽  
Delivery Outcomes ◽  
Virological Outcome ◽  
Adverse Pregnancy ◽  
Hiv 1

Abstract Background Safety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasma concentrations are reduced during second/third trimesters, with a potential risk of viral breakthroughs. Thus, French guidelines recommend switching to rilpivirine-free combinations (RFCs) during pregnancy. Objectives To describe the characteristics of women initiating pregnancy while on rilpivirine and to compare the outcomes for virologically suppressed subjects continuing rilpivirine until delivery versus switching to an RFC. Methods In the ANRS-EPF French Perinatal cohort, we included women on rilpivirine at conception in 2010–18. Pregnancy outcomes were compared between patients continuing versus interrupting rilpivirine. In women with documented viral suppression (<50 copies/mL) before 14 weeks of gestation (WG) while on rilpivirine, we compared the probability of viral rebound (≥50 copies/mL) during pregnancy between subjects continuing rilpivirine versus those switching to RFC. Results Among 247 women included, 88.7% had viral suppression at the beginning of pregnancy. Overall, 184 women (74.5%) switched to an RFC (mostly PI/ritonavir-based regimens) at a median gestational age of 8.0 WG. Plasma HIV-1 RNA nearest delivery was <50 copies/mL in 95.6% of women. Among 69 women with documented viral suppression before 14 WG, the risk of viral rebound was higher when switching to RFCs than when continuing rilpivirine (20.0% versus 0.0%, P = 0.046). Delivery outcomes were similar between groups (overall birth defects, 3.8/100 live births; pregnancy losses, 2.0%; preterm deliveries, 10.6%). No HIV transmission occurred. Conclusions In virologically suppressed women initiating pregnancy, continuing rilpivirine was associated with better virological outcome than changing regimen. We did not observe a higher risk of adverse pregnancy outcomes.

scholarly journals Assessment of HCMV-encoded microRNAs in Plasma as Potential Biomarkers in Pregnant Women with Adverse Pregnancy Outcomes

2020 ◽  
Author(s):  
Zhiying Gao ◽  
Likun Zhou ◽  
Jing Bai ◽  
Meng Ding ◽  
Deshui Liu ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Pregnancy Outcomes ◽  
Adverse Pregnancy Outcome ◽  
Expression Profiles ◽  
Plasma Concentrations ◽  
Adverse Pregnancy Outcomes ◽  
Immunoglobulin M ◽  
Validation Data ◽  
Adverse Pregnancy ◽  
Normal Controls

Abstract Background: Human cytomegalovirus (HCMV) is the most frequent cause of congenital infections and can lead to adverse pregnancy outcomes (APO). HCMV encodes multiple microRNAs (miRNAs) that have been reported to be partially related to host immune responses, cell cycle regulation, viral replication and viral latency, and can be detected in human plasma. However, the relevance of HCMV-encoded miRNAs in maternal plasma as an indicator for APO has never been evaluated.Methods: The expression profiles of 25 HCMV-encoded miRNAs were first measured in plasma samples from 20 pregnant women with APO and 28 normal controls by quantitative reverse-transcription polymerase chain reaction (RT-qPCR) technology. Next, markedly changed miRNAs were validated in another independent validation set consisting of 20 pregnant women with APO and 27 control subjects. HCMV DNA in peripheral blood leukocytes (PBLs) and anti-HCMV immunoglobulin M (IgM) and anti-HCMV immunoglobulin G (IgG) in plasma were also examined in both the training and validation sets. Diagnostic value and risk factors were compared between adverse pregnancy outcome cohorts and normal controls.Results: The analysis of training and validation data sets revealed that plasma concentrations of hcmv-miR-UL148D, hcmv-miR-US25-1-5p and hcmv-miR-US5-1 were obviously increased in pregnant women with APO compared with normal controls. Hcmv-miR-US25-1-5p presented the largest area under the receiver-operating characteristic (ROC) curve (0.735; 95% CI, 0.635–0.836), with a sensitivity of 68% and specificity of 71%. Furthermore, the plasma levels of hcmv-miR-US25-1-5p and hcmv-miR-US5-1 were obviously positively correlated with APO (P = 0.029 and 0.035, respectively). Nevertheless, neither the concentration of HCMV DNA in PBLs nor the positivity rates of anti-HCMV IgM and IgG in plasma showed statistically significant correlation with APO.Conclusion: We identified a unique signature of HCMV-encoded miRNAs in pregnant women with APO, which may be useful as a potential noninvasive biomarker for predicting and monitoring APO during HCMV infection.

scholarly journals Efficacy and safety of dolutegravir plus emtricitabine versus standard ART for the maintenance of HIV-1 suppression: 48-week results of the factorial, randomized, non-inferiority SIMPL’HIV trial

PLoS Medicine ◽  
2020 ◽  
Vol 17 (11) ◽  
pp. e1003421
Author(s):  
Delphine Sculier ◽  
Gilles Wandeler ◽  
Sabine Yerly ◽  
Annalisa Marinosci ◽  
Marcel Stoeckle ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Adverse Events ◽  
Viral Suppression ◽  
Safety Data ◽  
Risk Difference ◽  
Hiv Treatment ◽  
Efficacy And Safety ◽  
Open Label ◽  
Hiv 1

Background Dolutegravir (DTG)–based dual therapy is becoming a new paradigm for both the initiation and maintenance of HIV treatment. The SIMPL’HIV study investigated the outcomes of virologically suppressed patients on standard combination antiretroviral therapy (cART) switching to DTG + emtricitabine (FTC). We present the 48-week efficacy and safety data on DTG + FTC versus cART. Methods and findings SIMPL’HIV was a multicenter, open-label, non-inferiority randomized trial with a factorial design among treatment-experienced people with HIV in Switzerland. Participants were enrolled between 12 May 2017 and 30 May 2018. Patients virologically suppressed for at least 24 weeks on standard cART were randomized 1:1 to switching to DTG + FTC or to continuing cART, and 1:1 to simplified patient-centered monitoring versus standard monitoring. The primary endpoint was the proportion of patients virologically suppressed with <100 copies/ml through 48 weeks. The secondary endpoints included virological suppression at 48 weeks according to the US Food and Drug Administration (FDA) snapshot analysis. Non-inferiority of DTG + FTC versus cART for viral suppression was assessed using a stratified Mantel–Haenszel risk difference, with non-inferiority declared if the lower bound of the 95% confidence interval was greater than −12%. Adverse events were monitored to assess safety. Quality of life was evaluated using the PROQOL-HIV questionnaire. Ninety-three participants were randomized to DTG + FTC, and 94 individuals to cART. Median nadir CD4 count was 246 cells/mm3; median age was 48 years; 17% of participants were female. DTG + FTC was non-inferior to cART. The proportion of patients with viral suppression (<100 copies/ml) through 48 weeks was 93.5% in the DTG + FTC arm and 94.7% in the cART arm in the intention-to-treat population (risk difference −1.2%; 95% CI −7.8% to 5.6%). Per-protocol analysis showed similar results, with viral suppression in 96.5% of patients in both arms (risk difference 0.0%; 95% CI −5.6% to 5.5%). There was no relevant interaction between the type of treatment and monitoring (interaction ratio 0.98; 95% CI 0.85 to 1.13; p = 0.81). Using the FDA snapshot algorithm, 84/93 (90.3%) participants in the DTG + FTC arm had an HIV-1 RNA viral load of <50 copies/ml compared to 86/94 (91.5%) participants on standard cART (risk difference −1.1%; 95% CI −9.3% to 7.1%; p = 0.791). The overall proportion of patients with adverse events and discontinuations did not differ by randomization arm. The proportion of patients with serious adverse events was higher in the cART arm (16%) compared to the DTG + FTC arm (6.5%) (p = 0.041), but none was considered to be related to the study medication. Quality of life improved more between baseline and week 48 in the DTG + FTC compared to the cART arm (adjusted difference +2.6; 95% CI +0.4 to +4.7). The study’s main limitations included a rather small proportion of women included, the open label design, and its short duration. Conclusions In this study, DTG + FTC as maintenance therapy was non-inferior to cART in terms of efficacy, with a similar safety profile and a greater improvement in quality of life, thus expanding the offer of 2-drug simplification options among virologically suppressed individuals. Trial registration ClinicalTrials.gov NCT03160105.

Fostemsavir: The first oral attachment inhibitor for treatment of HIV-1 infection

2021 ◽  
Vol 78 (5) ◽  
pp. 376-388
Author(s):  
Elias B Chahine
Keyword(s):  
Adverse Reactions ◽  
Viral Suppression ◽  
Safety Data ◽  
Multidrug Resistant ◽  
Virologic Response ◽  
Phase 3 ◽  
Antiretroviral Therapies ◽  
Effective Option ◽  
Cytochrome P 450 ◽  
Hiv 1

Abstract Purpose The pharmacology, pharmacokinetics, and role in therapy of fostemsavir in management of HIV-1 infection are reviewed, with an emphasis on clinical efficacy and safety data from phase 2 and phase 3 clinical trials. Summary Fostemsavir (Rukobia, ViiV Healthcare), is a prodrug of temsavir, a novel pyridine compound with potent activity against HIV-1. Fostemsavir, the first oral attachment inhibitor, was approved and granted the breakthrough therapy designation by the Food and Drug Administration for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in heavily treatment-experienced adults. As absorption of temsavir is not altered with increased gastric pH, patients may take acid suppressive agents such as famotidine during fostemsavir therapy.Temsavir is primarily metabolized through hydrolysis but also via cytochrome P-450 (CYP) oxidation; therefore, coadministration of fostemsavir with strong CYP3A inducers such as rifampin, carbamazepine, phenytoin, mitotane, enzalutamide, or St John’s wort is contraindicated because it may result in significantly lower temsavir exposure, which can ultimately impair virologic response. The most common adverse reactions associated with fostemsavir use include nausea, diarrhea, headache, abdominal pain, dyspepsia, fatigue, rash, and sleep disturbance. Conclusion Fostemsavir may be an effective option for heavily treatment-experienced adults with multidrug-resistant HIV-1 infection. Fostemsavir is a particularly attractive treatment option for patients who are no longer able to achieve viral suppression with use of currently available antiretroviral therapies and who are able to adhere to a twice-daily oral regimen.

scholarly journals Ondansetron and pregnancy: Understanding the data

2015 ◽  
Vol 9 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Debra Kennedy
Keyword(s):  
Birth Defects ◽  
Pregnancy Outcomes ◽  
Safety Data ◽  
First Trimester ◽  
Common Condition ◽  
Off Label ◽  
Increased Risk ◽  
Practical Guidelines ◽  
Potential Risks ◽  
Adverse Pregnancy

Nausea and vomiting of pregnancy (NVP) is a common condition affecting 75% of pregnant women. NVP generally commences early in the first trimester, peaking in severity between 7 and 12 weeks and in over 90% symptoms will have abated by week 20. Thus, the time when women are most likely to have NVP and require treatment coincides with the embryonic period when there is maximum susceptibility to any teratogenic risk. Following the thalidomide tragedy of 55 years ago there is a particular awareness and sensitivity about these potential risks, especially in relation to any medication used to treat NVP. Despite several studies showing no clear benefits of ondansetron over other NVP treatments such as doxylamine, and the paucity of safety data, the off-label prescribing and use of ondansetron to treat NVP has increased significantly worldwide. Albeit based on limited human pregnancy data, ondansetron has not been associated with a significantly increased risk of birth defects or other adverse pregnancy outcomes. This review attempts to highlight some of the difficulties in interpreting the available data and the need to follow practical guidelines regarding treatment of NVP.

scholarly journals Weight Loss During Pregnancy Is Associated with Adverse Pregnancy Outcomes among HIV-1 Infected Women

2004 ◽  
Vol 134 (6) ◽  
pp. 1424-1431 ◽  
Author(s):  
Eduardo Villamor ◽  
Michele L. Dreyfuss ◽  
Ana Baylín ◽  
Gernard Msamanga ◽  
Wafaie W. Fawzi
Keyword(s):  
Weight Loss ◽  
Pregnancy Outcomes ◽  
Adverse Pregnancy Outcomes ◽  
Adverse Pregnancy ◽  
Hiv 1

scholarly journals A retrospective analysis of incident pregnancy in Phase 1 and 2a HIV-1 vaccine study participants does not support concern for adverse pregnancy or birth outcomes

2020 ◽  
Author(s):  
Lynda Stranix-Chibanda ◽  
Chenchen Yu ◽  
Margaret Brewinski Isaacs ◽  
Mary Allen ◽  
Jessica Andriesen ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pregnancy Outcomes ◽  
Phase 1 ◽  
Reproductive Potential ◽  
Vaccine Trials ◽  
Long Term Follow Up ◽  
Adverse Pregnancy ◽  
Hiv 1

Abstract Background: Pregnancies occur during HIV-1 vaccine clinical trials, despite requirements for women of reproductive potential to use effective contraception. Deployment of an effective HIV-1 vaccine regimen will likely target adolescents and young adults and therefore safety for pregnant and breastfeeding women will need to be addressed. Methods: We performed a retrospective, cross-protocol analysis to identify and compare pregnancy outcomes reported in 53 Phase 1 and Phase 2a HIV-1 vaccine clinical trials conducted by the HIV Vaccine Trials Network (HVTN). Results: 2673 women of reproductive potential were identified and 193 pregnancies were reported. 39 of 53 (74%) studies had at least one pregnancy reported with an overall pregnancy rate of 3.15 per 100 woman-years (w-yr). While active contraception use was required during study participation, 13 of the 53 studies also contained a long-term follow up period during which pregnancy was no longer discouraged. The pregnancy rate during main study participation was 3.09 per 100 w-yr, while pregnancies occurred at a slightly greater rate in the long-term follow up period (3.22 per 100 w-yr). Adverse pregnancy outcomes were reported at similar rates between vaccinees and placebo recipients when vaccine vectors, adjuvant used, or geographic region were examined. Conclusion: Although there is considerable heterogeneity amongst the different vaccine trials, there appears to be no obvious indication of increased risk of adverse pregnancy or birth outcomes in these early phase HIV-1 vaccine studies. More complete data on pregnancy outcomes should be collected in a systematic fashion in early phase HIV-1 vaccine clinical trials to better inform subsequent efficacy trials.

Delivery Outcomes of Pregnant Patients With Inflammatory Bowel Diseases Compared With the General Population and With Women With Other Autoimmune Diseases at a Tertiary Care Center

2020 ◽  
Author(s):  
Taylor Geisman ◽  
Ling Chen ◽  
Margaret Rosanna Gray-Swain ◽  
Deborah Hiatt-Jensen ◽  
Alexandra Gutierrez
Keyword(s):  
General Population ◽  
Autoimmune Diseases ◽  
Cesarean Delivery ◽  
Inflammatory Bowel Diseases ◽  
Pregnancy Outcomes ◽  
Cesarean Deliveries ◽  
Delivery Outcomes ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Adverse Pregnancy

Abstract Background Variable data have suggested that pregnant women with inflammatory bowel diseases (IBD) are more likely to have cesarean deliveries and adverse pregnancy outcomes than the general population. The aim of this study was to describe the rates of cesarean delivery and adverse pregnancy outcomes among patients with IBD as compared with patients with other autoimmune diseases and with the general population. Methods Pregnant patients with IBD, those with non-IBD autoimmune diseases, and control patients were identified. Baseline demographics, disease characteristics, medication use, and delivery outcomes were recorded in a retrospective manner. The primary outcome was overall rate of cesarean delivery; secondary outcomes included rates of planned and unplanned cesarean delivery, delivery complications, preterm delivery, and fetal complications. Results Ninety-three women with IBD were age-matched to 376 control patients; 38 women with other autoimmune diseases were also identified. Women with IBD had higher rates of cesarean delivery (47%) when compared with control patients (31%; P &lt; 0.0001) but not when compared with women with other autoimmune diseases. There were high rates of planned cesarean deliveries for IBD-related factors in the IBD cohort. Women with IBD did not have increased rates of adverse delivery or fetal outcomes. Conclusions Women with IBD have higher rates of cesarean delivery than the general population and rates similar to those of women with other autoimmune diseases. Planned cesarean delivery plays an important role in maintaining continuity and sphincter control in select situations, but a diagnosis of IBD does not mandate cesarean delivery.

scholarly journals A retrospective analysis of incident pregnancy in phase 1 and 2a HIV-1 vaccine study participants does not support concern for adverse pregnancy or birth outcomes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lynda Stranix-Chibanda ◽  
Chenchen Yu ◽  
Margaret Brewinski Isaacs ◽  
Mary Allen ◽  
Jessica Andriesen ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pregnancy Outcomes ◽  
Phase 1 ◽  
Reproductive Potential ◽  
Vaccine Trials ◽  
Long Term Follow Up ◽  
Adverse Pregnancy ◽  
Hiv 1

Abstract Background Pregnancies occur during HIV-1 vaccine clinical trials, despite requirements for women of reproductive potential to use effective contraception. Deployment of an effective HIV-1 vaccine regimen will likely target adolescents and young adults and therefore safety for pregnant and breastfeeding women will need to be addressed. Methods We performed a retrospective, cross-protocol analysis to identify and compare pregnancy outcomes reported in 53 Phase 1 and Phase 2a HIV-1 vaccine clinical trials conducted by the HIV Vaccine Trials Network (HVTN). Results Two thousand six hundred seventy-three women of reproductive potential were identified and 193 pregnancies were reported. 39 of 53 (74%) studies had at least one pregnancy reported with an overall pregnancy rate of 3.15 per 100 woman-years (w-yr). While active contraception use was required during study participation, 13 of the 53 studies also contained a long-term follow up period during which pregnancy was no longer discouraged. The pregnancy rate during main study participation was 3.09 per 100 w-yr, while pregnancies occurred at a slightly greater rate in the long-term follow up period (3.22 per 100 w-yr). Adverse pregnancy outcomes were reported at similar rates between vaccinees and placebo recipients when vaccine vectors, adjuvant used, or geographic region were examined. Conclusion Although there is considerable heterogeneity amongst the different vaccine trials, there appears to be no obvious indication of increased risk of adverse pregnancy or birth outcomes in these early phase HIV-1 vaccine studies. More complete data on pregnancy outcomes should be collected in early phase HIV-1 vaccine clinical trials to better inform subsequent efficacy trials.

Reproductive health issues in patients with psoriasis (literature review)

2019 ◽  
Vol 1 (7) ◽  
pp. 5-8
Author(s):  
L. S. Kruglova ◽  
A. A. Osina ◽  
A. A. Khotko
Keyword(s):  
Drug Therapy ◽  
Reproductive Health ◽  
Literature Review ◽  
Pregnancy Outcomes ◽  
Adverse Pregnancy Outcome ◽  
Certolizumab Pegol ◽  
Genetically Engineered ◽  
Health Issues ◽  
Degree Of Confidence ◽  
Adverse Pregnancy

Among patients with psoriasis, approximately 50% are women and almost 75 % of them are under the age of 40 years. Thus, most women with psoriasis have childbearing potential. When pregnancy occurs in 22 % of patients, the activity of psoriasis persists, characteristic of the course before pregnancy, in 23 % of women, the course of the disease worsens. The article provides up-to-date data on the management of pregnant patients with psoriasis. To improve pregnancy outcomes in patients with psoriasis, it is important to prevent exacerbation of the disease. The choice of drug therapy in this case is based on an assessment of the ratio of the risk of undesirable effects of the drugs on the developing fetus and the risk of the development of exacerbation of psoriasis, which can cause an adverse pregnancy outcome. Despite the fact that the available clinical experience of using genetically engineered drugs is still limited, with a certain degree of confidence we can say that there is no increase in the risk of adverse pregnancy outcomes associated with therapy with certolizumab pegol.

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