Etravirine pharmacokinetics in HIV-infected pregnant women

__Background__ The study goal was to describe etravirine pharmacokinetics during pregnancy and postpartum in HIV-infected women. __Methods__ IMPAACT P1026s and PANNA are on-going, non-randomized, open-label, parallel-group, multi-center phase-IV prospective studies in HIV-infected pregnant women. Intensive steady-state 12-h pharmacokinetic profiles were performed from 2nd trimester through postpartum. Etravirine was measured at two labs using validated ultra performance liquid chromatography (detection limits: 0.020 and 0.026 mcg/mL). __Results__ Fifteen women took etravirine 200 mg twice-daily. Etravirine AUC0-12 was higher in the 3rd trimester compared to paired postpartum data by 34% (median 8.3 vs. 5.3 mcg*h/mL, p = 0.068). Etravirine apparent oral clearance was significantly lower in the 3rd trimester of pregnancy compared to paired postpartum data by 52% (median 24 vs. 38 L/h, p = 0.025). The median ratio of cord blood to maternal plasma concentration at delivery was 0.52 (range: 0.19-4.25) and no perinatal transmission occurred. __Conclusion__ Etravirine apparent oral clearance is reduced and exposure increased during the third trimester of pregnancy. Based on prior dose-ranging and safety data, no dose adjustment is necessary for maternal health but the effects of etravirine in utero are unknown. Maternal health and infant outcomes should be closely monitored until further infant safety data are available. __Clinical Trial registration:__ The IMPAACT protocol P1026s and PANNA study are registered at ClinicalTrials.gov under NCT00042289 and NCT00825929

Influence of short-course antenatal antiretroviral therapy on viral load and mother-to-child transmission in subsequent pregnancies among HIV-infected women

Background HIV-infected women not requiring treatment for their own health usually receive short-course anti-retroviral therapy (ART) during pregnancy. Little is known about the effect of this on response to HAART in subsequent pregnancies. Methods We analysed data from the UK and Ireland's National Study of HIV in Pregnancy and Childhood for 2000–2010. Analyses were restricted to live births among women not on ART at conception but receiving antenatal HAART. We compared risk of detectable viral load at delivery and mother-to-child transmission in two pregnancy groups: ‘ART-naive’ and ‘HAART-experienced’ (≥7 days of HAART during previous pregnancy). Multivariable analyses were conducted using logistic regression. Results There were 5,372 pregnancies in the ART-naive group and 605 in the HAART-experienced group. Overall, there was weak evidence of an increased risk of detectable viral load in the HAART-experienced group (adjusted odds ratio [aOR] 1.27; 95% CI 1.01, 1.60); however, the increased risk was apparent only among women who previously received non-nucleoside reverse transcriptase inhibitor-based HAART (aOR 1.81; 95% CI 1.25, 2.63), and not among those with previous protease-inhibitor-based HAART exposure (aOR 1.08; 95% CI 0.81, 1.45). There was no difference in mother-to-child transmission risk between the ART-naive and HAART-experienced groups (aOR 0.42; 95% CI 0.10, 1.78), although the number of transmissions was small. Conclusions We found no increased risk of detectable viral load at delivery among women exposed to short-course, protease-inhibitor-based HAART during a previous pregnancy. However, women with prior exposure to non-nucleoside reverse transcriptase inhibitor-based HAART appeared to be at increased risk of not adequately suppressing the virus. These findings highlight the need for careful management of HIV-infected women presenting with repeat pregnancies. </jats:sec

A Review of Long-Term Toxicity of Antiretroviral Treatment Regimens and Implications for an Aging Population

<p></p><p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s40121-018-0201-6">https://link.springer.com/article/10.1007/s40121-018-0201-6</a></p><p></p><p></p><p> </p><p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p><br><p></p

Pregnant women with HIV infection can expect healthy survival: Three-year follow-up

OBJECTIVES: To document postpartum disease-free survival of HIV-infected women taking antiretroviral therapy (ART) during pregnancy. METHODS: Laboratory and clinical data were collected on all HIV-infected pregnant women delivering from 1998 to 2002 and followed up until September 2004 at 6 hospitals in London. Mothers were grouped according to receipt of zidovudine monotherapy (ZDVm), highly active antiretroviral therapy (HAART) given during and continued after pregnancy (cHAART), and short-term HAART given during pregnancy and discontinued on delivery (START). RESULTS: Eight-five women took ZDVm, 155 took cHAART, and 71 took START. The mean follow-up for all mothers was 33 months, with a total of 847 person-years. At the first antenatal clinic (ANC) visit, 72% of women were in Centers for Disease Control and Prevention (CDC) stage A, 85% were treatment naive, and the ZDVm group had a median HIV viral load (VL) 10-fold less than those mothers who started HAART during pregnancy. At last follow-up, 1 patient had died and 6 (1.9%) had progressed to CDC stage C; 62% of all women, including a quarter of the ZDVm group, were receiving HAART for their own health; and 83% of all mothers had a V

Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy

Objective: To assess the risks and benefits of administering highly active antiretroviral therapy (HAART) during the treatment of tuberculosis (TB) in HIV-infected patients. Design and methods: HIV-1 patients presenting to 12 HIV centres in Greater London and south-east England with culture-proven TB were identified from January 1996 to June 1999. Case-notes were reviewed retrospectively. Results: Patients (n = 188) were severely immunocompromised with a median CD4 cell count at TB diagnosis of 90 × 106 cells/l (IQR: 30–180). At presentation, 85% (n = 159) were not taking antiretrovirals. A total of 45% commenced HAART during TB treatment, which was associated with significant reductions in viral load, AIDS-defining illness (ADI) [3.5 versus 24.5%; relative risk (RR) = 0.14] and mortality. Only nine of 91 (10%) patients with a CD4 count > 100 × 106 cells/l at TB diagnosis experienced a further ADI, whereas 18 of 92 (20%) patients with a CD4 count < 100 × 106 cells/l developed this complication. Adverse events (AE) occurred in 99 (54%) of 183 patients, one-third of whom changed or interrupted HIV and/or TB medication. The majority of AE occurred within the first 2 months, with peripheral neuropathy (21%), rash (17%) and gastrointestinal upset (10%) occurring most commonly. Conclusions: Many physicians delay HAART in patients presenting with TB because of pill burden, drug/drug interactions and toxicity. Although the use of HAART led to significant reductions in viral load, ADI and mortality, co-infected patients commonly experienced AE leading to interruptions in TB/HIV therapy. We therefore recommend starting HAART early for patients with advanced HIV disease (CD4 100 × 106 cells/l)

Drug resistance genotypes predict response to amprenavir-containing regimens in highly drug-experienced HIV-1-infected patients

We have undertaken a study of virological responses to amprenavir-containing antiretroviral regimens, during the expanded access programme within the UK. Ninety-five HIV-1-infected patients were included for which virological and immunological follow-up was available for 75, and baseline drug resistance data available for 51. These were highly drug-experienced patients, having previously received a median of nine antiviral drugs, within all available classes. Eighty-eight percent of patients had a virological response to the new regimen, with a median maximal decline of 1.45 log10 copies/ml, and 34% of patients reached <400 copies/ml on treatment. Although 68% of patients with resistance data had protease inhibitor resistance mutations, only 10% patients had key amprenavir resistance mutations, and virological response was predicted by the number of active drugs utilized in the amprenavir-containing regimen, as determined by the baseline genotypic resistance test. Other independent predictors of viral load decline were a higher baseline viral load and fewer previous antiviral drugs. We conclude that amprenavir can contribute to antiviral efficacy in salvage regimens, and that resistance testing may help to optimize its use in this scenario. New formulations of amprenavir, together with boosted regimens, may enhance the activity in the presence of protease inhibitor-resistant virus