Neil Osterweil

BOSTON – In persons infected with HIV-1, with or without hepatitis C coinfections, specific circulating microRNAs may signal the presence of liver injury and progression, investigators stated.

An analysis of small RNA expression in plasma samples from 144 HIV-infected patients showed that two microRNAs (miRNAs) in the same family of RNA fragments were significantly upregulated in patients with HIV-1 and HCV coinfections that progressed to liver cirrhosis, despite the patients having no evidence of liver fibrosis at the time of plasma sampling, reported Miguel Angel Martinez, PhD, of IrsiCaixa AIDS Research Institute in Badalona, Spain.

SOURCE: Martinez MA et al. CROI 2018, abstract 639.

BOSTON – In persons infected with HIV-1, with or without hepatitis C coinfections, specific circulating microRNAs may signal the presence of liver injury and progression, investigators stated.

An analysis of small RNA expression in plasma samples from 144 HIV-infected patients showed that two microRNAs (miRNAs) in the same family of RNA fragments were significantly upregulated in patients with HIV-1 and HCV coinfections that progressed to liver cirrhosis, despite the patients having no evidence of liver fibrosis at the time of plasma sampling, reported Miguel Angel Martinez, PhD, of IrsiCaixa AIDS Research Institute in Badalona, Spain.

SOURCE: Martinez MA et al. CROI 2018, abstract 639.

BOSTON – In persons infected with HIV-1, with or without hepatitis C coinfections, specific circulating microRNAs may signal the presence of liver injury and progression, investigators stated.

An analysis of small RNA expression in plasma samples from 144 HIV-infected patients showed that two microRNAs (miRNAs) in the same family of RNA fragments were significantly upregulated in patients with HIV-1 and HCV coinfections that progressed to liver cirrhosis, despite the patients having no evidence of liver fibrosis at the time of plasma sampling, reported Miguel Angel Martinez, PhD, of IrsiCaixa AIDS Research Institute in Badalona, Spain.

SOURCE: Martinez MA et al. CROI 2018, abstract 639.

BOSTON – World Health Organization guidelines on the use of isoniazid to prevent tuberculosis in HIV-infected women during pregnancy may need to be reconsidered in light of new evidence that isoniazid preventive therapy (IPT) is associated with a high risk for adverse pregnancy events, investigators say.

Among 156 HIV-infected pregnant women, the rate of adverse pregnancy outcomes was 23% for those randomly assigned to immediate IPT during pregnancy versus 17% for women randomized to IPT that was delayed until 12 weeks postpartum, a significant difference (P = .009), reported Amita Gupta, MD, from Johns Hopkins University in Baltimore.

KatarzynaBialasiewicz/thinkstockphotos

However, the quality of evidence to support that statement is weak, primarily because pregnant women were typically excluded from IPT or other tuberculosis-prevention trials. In addition, isoniazid has been associated in retrospective studies with increased hepatotoxicity in women both during pregnancy and in the postpartum period, Dr. Gupta pointed out.

She and her colleagues conducted the phase 4 IMPAACT P1078 trial to test the hypothesis that IPT can be initiated safely during pregnancy. The study was conducted at centers in Botswana, Haiti, India, South Africa, Tanzania, Thailand, Uganda, and Zimbabwe.

HIV-infected pregnant women from 14 through 34 weeks of gestation who live in a high TB burden area (prevalence of 60 cases or more per 100,000 population) but had no evidence of TB infection were randomly assigned on a 1:1 basis to receive either immediate therapy with isoniazid 300 mg daily for 28 weeks, followed by placebo, or to the same dose of isoniazid started 12 weeks postpartum for 28 weeks. All patients also received vitamin B6 and a prenatal multivitamin until 40 weeks postpartum.

The participants were stratified by gestational age (14 to less than 24 weeks and 24 through 34 weeks). Women were excluded if they were suspected of having active TB, reported recent exposure, or had received TB treatment for more than 30 days in the past year. Women with recent acute hepatitis or peripheral neuropathy were excluded.

All women and their infants received the local standard of care for HIV. The investigators performed intensified TB case finding by using the WHO symptoms screening and exam, monitoring of signs and symptoms, conducting liver function tests, and screening for peripheral neuropathy.

“We had higher than expected adverse events in the study, but there was no statistical difference between arms,” she said.

In an intention-to-treat analysis, the rate of first maternal treatment-related grade 3 or greater adverse event or permanent drug discontinuation caused by toxicity (the primary endpoint) was 15.5% in the immediate IPT arm and 15.2% in the delayed IPT arm, a nonsignificant difference. The immediate therapy arm approached but did not quite reach the prespecified boundary of noninferiority, Dr. Gupta noted.

The per-protocol analysis of the primary endpoint was similar, at 17.6% vs. 17.8%, respectively.

In the intention-to-treat analysis, any-cause grade 3 or greater maternal adverse events were seen in 30.5% of women in the immediate arm versus 28.4% in the delayed arm, with an incidence-rate difference of 4.2 per 100 person-years, which did not reach the noninferiority boundary.

The respective rates in the per-protocol analysis were 33% vs. 30.4%, for an incidence-rate difference of 4.3 per 100 person-years.

In both groups, elevated liver enzymes and weight loss were the most common maternal adverse events.

All cause hepatotoxicity occurred in 6% of participants in the immediate arm and 7% in the deferred. Rates of permanent discontinuation because of toxicity were 4% and 6%, respectively, along with the two women in the immediate IPT arm and four in the delayed arm who died during the study. There were no significant differences in these outcomes between the groups.

Dr. Gupta noted that higher liver function test results were seen after delivery, regardless of whether the women were on IPT or what type of antiretroviral therapy they were receiving.

There were no significant differences seen in infant safety by treatment arm, a secondary endpoint.

“What did we learn? We learned that we had higher than expected adverse events that were at least possibly attributed to IPT in both arms. We did not reach our noninferiority margin partly because of the high rates, but we also did not find any major significant differences between the immediate and the deferred arm in terms of maternal safety when it was looked [at] by itself,” she said.

Although there were no significant differences in any maternal hepatotoxicity, grade 3 or greater infant adverse events, or maternal or infant death by treatment arm, “we did find an important distinction in terms of difference by adverse pregnancy outcomes, where immediate IPT was associated with more adverse pregnancy outcomes,” she said,

SOURCE: Gupta A et al. CROI 2018, Abstract Number 142LB.

BOSTON – World Health Organization guidelines on the use of isoniazid to prevent tuberculosis in HIV-infected women during pregnancy may need to be reconsidered in light of new evidence that isoniazid preventive therapy (IPT) is associated with a high risk for adverse pregnancy events, investigators say.

Among 156 HIV-infected pregnant women, the rate of adverse pregnancy outcomes was 23% for those randomly assigned to immediate IPT during pregnancy versus 17% for women randomized to IPT that was delayed until 12 weeks postpartum, a significant difference (P = .009), reported Amita Gupta, MD, from Johns Hopkins University in Baltimore.

KatarzynaBialasiewicz/thinkstockphotos

However, the quality of evidence to support that statement is weak, primarily because pregnant women were typically excluded from IPT or other tuberculosis-prevention trials. In addition, isoniazid has been associated in retrospective studies with increased hepatotoxicity in women both during pregnancy and in the postpartum period, Dr. Gupta pointed out.

She and her colleagues conducted the phase 4 IMPAACT P1078 trial to test the hypothesis that IPT can be initiated safely during pregnancy. The study was conducted at centers in Botswana, Haiti, India, South Africa, Tanzania, Thailand, Uganda, and Zimbabwe.

HIV-infected pregnant women from 14 through 34 weeks of gestation who live in a high TB burden area (prevalence of 60 cases or more per 100,000 population) but had no evidence of TB infection were randomly assigned on a 1:1 basis to receive either immediate therapy with isoniazid 300 mg daily for 28 weeks, followed by placebo, or to the same dose of isoniazid started 12 weeks postpartum for 28 weeks. All patients also received vitamin B6 and a prenatal multivitamin until 40 weeks postpartum.

The participants were stratified by gestational age (14 to less than 24 weeks and 24 through 34 weeks). Women were excluded if they were suspected of having active TB, reported recent exposure, or had received TB treatment for more than 30 days in the past year. Women with recent acute hepatitis or peripheral neuropathy were excluded.

All women and their infants received the local standard of care for HIV. The investigators performed intensified TB case finding by using the WHO symptoms screening and exam, monitoring of signs and symptoms, conducting liver function tests, and screening for peripheral neuropathy.

“We had higher than expected adverse events in the study, but there was no statistical difference between arms,” she said.

In an intention-to-treat analysis, the rate of first maternal treatment-related grade 3 or greater adverse event or permanent drug discontinuation caused by toxicity (the primary endpoint) was 15.5% in the immediate IPT arm and 15.2% in the delayed IPT arm, a nonsignificant difference. The immediate therapy arm approached but did not quite reach the prespecified boundary of noninferiority, Dr. Gupta noted.

The per-protocol analysis of the primary endpoint was similar, at 17.6% vs. 17.8%, respectively.

In the intention-to-treat analysis, any-cause grade 3 or greater maternal adverse events were seen in 30.5% of women in the immediate arm versus 28.4% in the delayed arm, with an incidence-rate difference of 4.2 per 100 person-years, which did not reach the noninferiority boundary.

The respective rates in the per-protocol analysis were 33% vs. 30.4%, for an incidence-rate difference of 4.3 per 100 person-years.

In both groups, elevated liver enzymes and weight loss were the most common maternal adverse events.

All cause hepatotoxicity occurred in 6% of participants in the immediate arm and 7% in the deferred. Rates of permanent discontinuation because of toxicity were 4% and 6%, respectively, along with the two women in the immediate IPT arm and four in the delayed arm who died during the study. There were no significant differences in these outcomes between the groups.

Dr. Gupta noted that higher liver function test results were seen after delivery, regardless of whether the women were on IPT or what type of antiretroviral therapy they were receiving.

There were no significant differences seen in infant safety by treatment arm, a secondary endpoint.

“What did we learn? We learned that we had higher than expected adverse events that were at least possibly attributed to IPT in both arms. We did not reach our noninferiority margin partly because of the high rates, but we also did not find any major significant differences between the immediate and the deferred arm in terms of maternal safety when it was looked [at] by itself,” she said.

Although there were no significant differences in any maternal hepatotoxicity, grade 3 or greater infant adverse events, or maternal or infant death by treatment arm, “we did find an important distinction in terms of difference by adverse pregnancy outcomes, where immediate IPT was associated with more adverse pregnancy outcomes,” she said,

SOURCE: Gupta A et al. CROI 2018, Abstract Number 142LB.

BOSTON – World Health Organization guidelines on the use of isoniazid to prevent tuberculosis in HIV-infected women during pregnancy may need to be reconsidered in light of new evidence that isoniazid preventive therapy (IPT) is associated with a high risk for adverse pregnancy events, investigators say.

Among 156 HIV-infected pregnant women, the rate of adverse pregnancy outcomes was 23% for those randomly assigned to immediate IPT during pregnancy versus 17% for women randomized to IPT that was delayed until 12 weeks postpartum, a significant difference (P = .009), reported Amita Gupta, MD, from Johns Hopkins University in Baltimore.

KatarzynaBialasiewicz/thinkstockphotos

However, the quality of evidence to support that statement is weak, primarily because pregnant women were typically excluded from IPT or other tuberculosis-prevention trials. In addition, isoniazid has been associated in retrospective studies with increased hepatotoxicity in women both during pregnancy and in the postpartum period, Dr. Gupta pointed out.

She and her colleagues conducted the phase 4 IMPAACT P1078 trial to test the hypothesis that IPT can be initiated safely during pregnancy. The study was conducted at centers in Botswana, Haiti, India, South Africa, Tanzania, Thailand, Uganda, and Zimbabwe.

HIV-infected pregnant women from 14 through 34 weeks of gestation who live in a high TB burden area (prevalence of 60 cases or more per 100,000 population) but had no evidence of TB infection were randomly assigned on a 1:1 basis to receive either immediate therapy with isoniazid 300 mg daily for 28 weeks, followed by placebo, or to the same dose of isoniazid started 12 weeks postpartum for 28 weeks. All patients also received vitamin B6 and a prenatal multivitamin until 40 weeks postpartum.

The participants were stratified by gestational age (14 to less than 24 weeks and 24 through 34 weeks). Women were excluded if they were suspected of having active TB, reported recent exposure, or had received TB treatment for more than 30 days in the past year. Women with recent acute hepatitis or peripheral neuropathy were excluded.

All women and their infants received the local standard of care for HIV. The investigators performed intensified TB case finding by using the WHO symptoms screening and exam, monitoring of signs and symptoms, conducting liver function tests, and screening for peripheral neuropathy.

“We had higher than expected adverse events in the study, but there was no statistical difference between arms,” she said.

In an intention-to-treat analysis, the rate of first maternal treatment-related grade 3 or greater adverse event or permanent drug discontinuation caused by toxicity (the primary endpoint) was 15.5% in the immediate IPT arm and 15.2% in the delayed IPT arm, a nonsignificant difference. The immediate therapy arm approached but did not quite reach the prespecified boundary of noninferiority, Dr. Gupta noted.

The per-protocol analysis of the primary endpoint was similar, at 17.6% vs. 17.8%, respectively.

In the intention-to-treat analysis, any-cause grade 3 or greater maternal adverse events were seen in 30.5% of women in the immediate arm versus 28.4% in the delayed arm, with an incidence-rate difference of 4.2 per 100 person-years, which did not reach the noninferiority boundary.

The respective rates in the per-protocol analysis were 33% vs. 30.4%, for an incidence-rate difference of 4.3 per 100 person-years.

In both groups, elevated liver enzymes and weight loss were the most common maternal adverse events.

All cause hepatotoxicity occurred in 6% of participants in the immediate arm and 7% in the deferred. Rates of permanent discontinuation because of toxicity were 4% and 6%, respectively, along with the two women in the immediate IPT arm and four in the delayed arm who died during the study. There were no significant differences in these outcomes between the groups.

Dr. Gupta noted that higher liver function test results were seen after delivery, regardless of whether the women were on IPT or what type of antiretroviral therapy they were receiving.

There were no significant differences seen in infant safety by treatment arm, a secondary endpoint.

“What did we learn? We learned that we had higher than expected adverse events that were at least possibly attributed to IPT in both arms. We did not reach our noninferiority margin partly because of the high rates, but we also did not find any major significant differences between the immediate and the deferred arm in terms of maternal safety when it was looked [at] by itself,” she said.

Although there were no significant differences in any maternal hepatotoxicity, grade 3 or greater infant adverse events, or maternal or infant death by treatment arm, “we did find an important distinction in terms of difference by adverse pregnancy outcomes, where immediate IPT was associated with more adverse pregnancy outcomes,” she said,

SOURCE: Gupta A et al. CROI 2018, Abstract Number 142LB.

Men who dread the prospect of multicore prostate biopsies can take heart in the news that multiparametric MRI with or without targeted biopsy was noninferior to transrectal ultrasound at detecting clinically significant cancers, results of a multicenter randomized trial indicate.

The rate of clinically significant cancers detected in men with clinical suspicion of prostate cancer who were randomly assigned to undergo MRI was 38%, compared with 26% (P = .005) for men assigned to standard transrectal ultrasound guided biopsy with 10 or 12 biopsy cores, reported Veeru Kasivisvanathan, MRCS, of University College London, and colleagues in the PRECISION trial (Prostate Evaluation for Clinically Important Disease: Sampling Using Image-guidance or Not?).

Significantly fewer men assigned to MRI-targeted biopsy were diagnosed with clinically insignificant cancers, suggesting that MRI could help to reduce the number of invasive biopsies and the associated pain, discomfort, and infection risks, the investigators stated in the New England Journal of Medicine.

“MRI, with or without targeted biopsy, led to fewer men undergoing biopsy, more clinically significant cancers being identified, less overdetection of clinically insignificant cancer, and fewer biopsy cores being obtained than did standard transrectal ultrasonography-guided biopsy,” they wrote.

Multiparametric MRI combines several different imaging modalities, including standard T1- and T2-weighted scans with dynamic contrast–enhanced and/or diffusion-weighted imaging to provide a wealth of information to aid in diagnosis. The technique has been shown in single-center studies to be similar or superior to ultrasound guided biopsy at detecting clinically significant cancers and minimizing detection of cancers that turn out to be clinically insignificant, the investigators said.

To add to the body of evidence, investigators from 25 centers in 11 countries randomized a total of 500 men with clinical suspicion of prostate cancer and no history of prostate biopsy to undergo either MRI plus targeted biopsy (not 10- or 12-core biopsy) if the scans indicated suspicion of malignancy, or standard transrectal ultrasound-guided biopsy with 10 or 12 core samples.

The investigators defined clinically significant cancer as the presence of a single biopsy core indicating disease of Gleason score 3 plus 4 (Gleason sum of 7), or greater.

SOURCE: Kasivisvanathan V et al. N Engl J Med. 2018 Mar 19. doi: 10.1056/NEJMoa1801993.

Men who dread the prospect of multicore prostate biopsies can take heart in the news that multiparametric MRI with or without targeted biopsy was noninferior to transrectal ultrasound at detecting clinically significant cancers, results of a multicenter randomized trial indicate.

The rate of clinically significant cancers detected in men with clinical suspicion of prostate cancer who were randomly assigned to undergo MRI was 38%, compared with 26% (P = .005) for men assigned to standard transrectal ultrasound guided biopsy with 10 or 12 biopsy cores, reported Veeru Kasivisvanathan, MRCS, of University College London, and colleagues in the PRECISION trial (Prostate Evaluation for Clinically Important Disease: Sampling Using Image-guidance or Not?).

Significantly fewer men assigned to MRI-targeted biopsy were diagnosed with clinically insignificant cancers, suggesting that MRI could help to reduce the number of invasive biopsies and the associated pain, discomfort, and infection risks, the investigators stated in the New England Journal of Medicine.

“MRI, with or without targeted biopsy, led to fewer men undergoing biopsy, more clinically significant cancers being identified, less overdetection of clinically insignificant cancer, and fewer biopsy cores being obtained than did standard transrectal ultrasonography-guided biopsy,” they wrote.

Multiparametric MRI combines several different imaging modalities, including standard T1- and T2-weighted scans with dynamic contrast–enhanced and/or diffusion-weighted imaging to provide a wealth of information to aid in diagnosis. The technique has been shown in single-center studies to be similar or superior to ultrasound guided biopsy at detecting clinically significant cancers and minimizing detection of cancers that turn out to be clinically insignificant, the investigators said.

To add to the body of evidence, investigators from 25 centers in 11 countries randomized a total of 500 men with clinical suspicion of prostate cancer and no history of prostate biopsy to undergo either MRI plus targeted biopsy (not 10- or 12-core biopsy) if the scans indicated suspicion of malignancy, or standard transrectal ultrasound-guided biopsy with 10 or 12 core samples.

The investigators defined clinically significant cancer as the presence of a single biopsy core indicating disease of Gleason score 3 plus 4 (Gleason sum of 7), or greater.

SOURCE: Kasivisvanathan V et al. N Engl J Med. 2018 Mar 19. doi: 10.1056/NEJMoa1801993.

Men who dread the prospect of multicore prostate biopsies can take heart in the news that multiparametric MRI with or without targeted biopsy was noninferior to transrectal ultrasound at detecting clinically significant cancers, results of a multicenter randomized trial indicate.

The rate of clinically significant cancers detected in men with clinical suspicion of prostate cancer who were randomly assigned to undergo MRI was 38%, compared with 26% (P = .005) for men assigned to standard transrectal ultrasound guided biopsy with 10 or 12 biopsy cores, reported Veeru Kasivisvanathan, MRCS, of University College London, and colleagues in the PRECISION trial (Prostate Evaluation for Clinically Important Disease: Sampling Using Image-guidance or Not?).

Significantly fewer men assigned to MRI-targeted biopsy were diagnosed with clinically insignificant cancers, suggesting that MRI could help to reduce the number of invasive biopsies and the associated pain, discomfort, and infection risks, the investigators stated in the New England Journal of Medicine.

“MRI, with or without targeted biopsy, led to fewer men undergoing biopsy, more clinically significant cancers being identified, less overdetection of clinically insignificant cancer, and fewer biopsy cores being obtained than did standard transrectal ultrasonography-guided biopsy,” they wrote.

Multiparametric MRI combines several different imaging modalities, including standard T1- and T2-weighted scans with dynamic contrast–enhanced and/or diffusion-weighted imaging to provide a wealth of information to aid in diagnosis. The technique has been shown in single-center studies to be similar or superior to ultrasound guided biopsy at detecting clinically significant cancers and minimizing detection of cancers that turn out to be clinically insignificant, the investigators said.

To add to the body of evidence, investigators from 25 centers in 11 countries randomized a total of 500 men with clinical suspicion of prostate cancer and no history of prostate biopsy to undergo either MRI plus targeted biopsy (not 10- or 12-core biopsy) if the scans indicated suspicion of malignancy, or standard transrectal ultrasound-guided biopsy with 10 or 12 core samples.

The investigators defined clinically significant cancer as the presence of a single biopsy core indicating disease of Gleason score 3 plus 4 (Gleason sum of 7), or greater.

SOURCE: Kasivisvanathan V et al. N Engl J Med. 2018 Mar 19. doi: 10.1056/NEJMoa1801993.

BOSTON – Efavirenz-based antiretroviral therapy may significantly impair the effectiveness of vaginal ring contraceptives, investigators reported.

Over a 21-day period, levels of estrogen among women who used a vaginal ring (NuvaRing) while on efavirenz-based antiretroviral therapy (ART) were up to 79% lower, and levels of progestin were up to 57% lower, than in women with HIV infection who used the vaginal ring before starting ART, reported Kimberly K. Scarsi, PharmD, of the University of Nebraska, Omaha.

In contrast, women on an atazanavir-based ART regimen had lower estrogen levels than untreated controls who used a vaginal ring, but higher levels of progestin – the primary antiovulatory component of the ring – suggesting that it would retain contraceptive effectiveness, she said at the annual Conference on Retroviruses and Opportunistic Infections.

“In a broader context, these data can be applied to other drugs that behave similarly. So for example, erythromycins are also known to interfere with hormones in this way, as well as some anticonvulsant agents that may also impair the effectiveness of vaginal ring contraceptives,” she said at a brief, following her presentation of the data in an oral abstract session.

The geometric mean ratios for the efavirenz group at 7, 14, and 21 days versus controls were 0.21, 0.22, and 0.24 (P less than .05 for all comparisons). In the atazanavir group, the respective geometric mean ratios were 1.71, 1.79, and 1.74 (P less than .05 for all comparisons).

SOURCE: Scarsi KK et al. CROI 2018, Abstract 141.

BOSTON – Efavirenz-based antiretroviral therapy may significantly impair the effectiveness of vaginal ring contraceptives, investigators reported.

Over a 21-day period, levels of estrogen among women who used a vaginal ring (NuvaRing) while on efavirenz-based antiretroviral therapy (ART) were up to 79% lower, and levels of progestin were up to 57% lower, than in women with HIV infection who used the vaginal ring before starting ART, reported Kimberly K. Scarsi, PharmD, of the University of Nebraska, Omaha.

In contrast, women on an atazanavir-based ART regimen had lower estrogen levels than untreated controls who used a vaginal ring, but higher levels of progestin – the primary antiovulatory component of the ring – suggesting that it would retain contraceptive effectiveness, she said at the annual Conference on Retroviruses and Opportunistic Infections.

“In a broader context, these data can be applied to other drugs that behave similarly. So for example, erythromycins are also known to interfere with hormones in this way, as well as some anticonvulsant agents that may also impair the effectiveness of vaginal ring contraceptives,” she said at a brief, following her presentation of the data in an oral abstract session.

The geometric mean ratios for the efavirenz group at 7, 14, and 21 days versus controls were 0.21, 0.22, and 0.24 (P less than .05 for all comparisons). In the atazanavir group, the respective geometric mean ratios were 1.71, 1.79, and 1.74 (P less than .05 for all comparisons).

SOURCE: Scarsi KK et al. CROI 2018, Abstract 141.

BOSTON – Efavirenz-based antiretroviral therapy may significantly impair the effectiveness of vaginal ring contraceptives, investigators reported.

Over a 21-day period, levels of estrogen among women who used a vaginal ring (NuvaRing) while on efavirenz-based antiretroviral therapy (ART) were up to 79% lower, and levels of progestin were up to 57% lower, than in women with HIV infection who used the vaginal ring before starting ART, reported Kimberly K. Scarsi, PharmD, of the University of Nebraska, Omaha.

In contrast, women on an atazanavir-based ART regimen had lower estrogen levels than untreated controls who used a vaginal ring, but higher levels of progestin – the primary antiovulatory component of the ring – suggesting that it would retain contraceptive effectiveness, she said at the annual Conference on Retroviruses and Opportunistic Infections.

“In a broader context, these data can be applied to other drugs that behave similarly. So for example, erythromycins are also known to interfere with hormones in this way, as well as some anticonvulsant agents that may also impair the effectiveness of vaginal ring contraceptives,” she said at a brief, following her presentation of the data in an oral abstract session.

The geometric mean ratios for the efavirenz group at 7, 14, and 21 days versus controls were 0.21, 0.22, and 0.24 (P less than .05 for all comparisons). In the atazanavir group, the respective geometric mean ratios were 1.71, 1.79, and 1.74 (P less than .05 for all comparisons).

SOURCE: Scarsi KK et al. CROI 2018, Abstract 141.

Using the PARP inhibitor veliparib as a radiosensitizer for chest wall radiation in women with inflammatory or locally recurrent breast cancer was associated with a high rate of late grade 3 adverse events, results of a phase 1 study show.

Although the trial’s upper limit of dose-limiting toxicities during 6 weeks of treatment and 4 weeks of follow-up was not met, 46.7% of 30 patients treated with veliparib and radiation after complete surgical resection had at least one grade 3 adverse event by 3 years of follow-up, reported Reshma Jagsi, MD, of the University of Michigan, Ann Arbor.

“In this multicenter phase 1 trial, severe acute toxicity did not exceed the prespecified target of 30%, even at the highest tested dose of veliparib (200 mg twice a day), and we observed no grade 4 or 5 events. However, given observations of grade 3 late toxicity in nearly one-half of all patients evaluated at 3 years, we recommend a phase 2 dose of 50 mg twice a day if veliparib is investigated further for radiosensitization in patients with breast cancer at high risk of locoregional recurrence and in need of treatment intensification,” they wrote in the Journal of Clinical Oncology.

In preclinical studies, PARP (poly [ADP-ribose] polymerase) inhibitors have been shown to enhance radiosensitivty of breast malignancies when given concurrently with radiation.

In a phase 1 dosing and safety study, 30 women with inflammatory or locally recurrent breast cancer of the chest wall underwent complete surgical resection and were then assigned to radiation consisting of 50 Gy to the chest wall and regional lymph nodes, plus a 10 Gy boost. The patients also received oral veliparib at a dose of either 50, 100, 150, or 200 mg taken twice daily during the 6-week course of radiotherapy.

During the 6 weeks of therapy and 4 weeks of follow-up, there were five dose-limiting toxicities, including two cases each of confluent moist desquamation greater than 100 cm² in the 100- and 150-mg dose groups, and one case of neutropenia in a patient at the 200-mg dose level.

The respective rates of any grade 3 toxicity, treatment related or otherwise, at 1, 2, and 3 years of follow-up were 10%, 16.7%, and 46.7%.

The investigators noted that, at year 3, severe fibrosis in the treatment field was seen in 6 of the 15 surviving patients. Of the six patients, two also had grade 3 skin induration, and two had grade 3 lymphedema.

“Although some of the late adverse events we observed might have occurred even in the absence of the investigational agent and with standard therapy, severe late toxicity is relatively uncommon with standard therapy alone, so we believe that a cautious approach is prudent,” Dr. Jagsi and associates wrote.

The study was supported by the Translational Breast Cancer Research Consortium, Breast Cancer Research Foundation, University of Michigan Comprehensive Cancer Center, and Michigan Institute for Clinical and Health Research. Dr. Jagsi reported institutional research support from AbbVie, which donated the veliparib used in the study.

SOURCE: Jagsi R et al. J Clin Oncol. 2018 Mar 20. doi: 10.1200/JCO.2017.77.2665

Using the PARP inhibitor veliparib as a radiosensitizer for chest wall radiation in women with inflammatory or locally recurrent breast cancer was associated with a high rate of late grade 3 adverse events, results of a phase 1 study show.

Although the trial’s upper limit of dose-limiting toxicities during 6 weeks of treatment and 4 weeks of follow-up was not met, 46.7% of 30 patients treated with veliparib and radiation after complete surgical resection had at least one grade 3 adverse event by 3 years of follow-up, reported Reshma Jagsi, MD, of the University of Michigan, Ann Arbor.

“In this multicenter phase 1 trial, severe acute toxicity did not exceed the prespecified target of 30%, even at the highest tested dose of veliparib (200 mg twice a day), and we observed no grade 4 or 5 events. However, given observations of grade 3 late toxicity in nearly one-half of all patients evaluated at 3 years, we recommend a phase 2 dose of 50 mg twice a day if veliparib is investigated further for radiosensitization in patients with breast cancer at high risk of locoregional recurrence and in need of treatment intensification,” they wrote in the Journal of Clinical Oncology.

In preclinical studies, PARP (poly [ADP-ribose] polymerase) inhibitors have been shown to enhance radiosensitivty of breast malignancies when given concurrently with radiation.

In a phase 1 dosing and safety study, 30 women with inflammatory or locally recurrent breast cancer of the chest wall underwent complete surgical resection and were then assigned to radiation consisting of 50 Gy to the chest wall and regional lymph nodes, plus a 10 Gy boost. The patients also received oral veliparib at a dose of either 50, 100, 150, or 200 mg taken twice daily during the 6-week course of radiotherapy.

During the 6 weeks of therapy and 4 weeks of follow-up, there were five dose-limiting toxicities, including two cases each of confluent moist desquamation greater than 100 cm² in the 100- and 150-mg dose groups, and one case of neutropenia in a patient at the 200-mg dose level.

The respective rates of any grade 3 toxicity, treatment related or otherwise, at 1, 2, and 3 years of follow-up were 10%, 16.7%, and 46.7%.

The investigators noted that, at year 3, severe fibrosis in the treatment field was seen in 6 of the 15 surviving patients. Of the six patients, two also had grade 3 skin induration, and two had grade 3 lymphedema.

“Although some of the late adverse events we observed might have occurred even in the absence of the investigational agent and with standard therapy, severe late toxicity is relatively uncommon with standard therapy alone, so we believe that a cautious approach is prudent,” Dr. Jagsi and associates wrote.

The study was supported by the Translational Breast Cancer Research Consortium, Breast Cancer Research Foundation, University of Michigan Comprehensive Cancer Center, and Michigan Institute for Clinical and Health Research. Dr. Jagsi reported institutional research support from AbbVie, which donated the veliparib used in the study.

SOURCE: Jagsi R et al. J Clin Oncol. 2018 Mar 20. doi: 10.1200/JCO.2017.77.2665

Using the PARP inhibitor veliparib as a radiosensitizer for chest wall radiation in women with inflammatory or locally recurrent breast cancer was associated with a high rate of late grade 3 adverse events, results of a phase 1 study show.

Although the trial’s upper limit of dose-limiting toxicities during 6 weeks of treatment and 4 weeks of follow-up was not met, 46.7% of 30 patients treated with veliparib and radiation after complete surgical resection had at least one grade 3 adverse event by 3 years of follow-up, reported Reshma Jagsi, MD, of the University of Michigan, Ann Arbor.

“In this multicenter phase 1 trial, severe acute toxicity did not exceed the prespecified target of 30%, even at the highest tested dose of veliparib (200 mg twice a day), and we observed no grade 4 or 5 events. However, given observations of grade 3 late toxicity in nearly one-half of all patients evaluated at 3 years, we recommend a phase 2 dose of 50 mg twice a day if veliparib is investigated further for radiosensitization in patients with breast cancer at high risk of locoregional recurrence and in need of treatment intensification,” they wrote in the Journal of Clinical Oncology.

In preclinical studies, PARP (poly [ADP-ribose] polymerase) inhibitors have been shown to enhance radiosensitivty of breast malignancies when given concurrently with radiation.

In a phase 1 dosing and safety study, 30 women with inflammatory or locally recurrent breast cancer of the chest wall underwent complete surgical resection and were then assigned to radiation consisting of 50 Gy to the chest wall and regional lymph nodes, plus a 10 Gy boost. The patients also received oral veliparib at a dose of either 50, 100, 150, or 200 mg taken twice daily during the 6-week course of radiotherapy.

During the 6 weeks of therapy and 4 weeks of follow-up, there were five dose-limiting toxicities, including two cases each of confluent moist desquamation greater than 100 cm² in the 100- and 150-mg dose groups, and one case of neutropenia in a patient at the 200-mg dose level.

The respective rates of any grade 3 toxicity, treatment related or otherwise, at 1, 2, and 3 years of follow-up were 10%, 16.7%, and 46.7%.

The investigators noted that, at year 3, severe fibrosis in the treatment field was seen in 6 of the 15 surviving patients. Of the six patients, two also had grade 3 skin induration, and two had grade 3 lymphedema.

“Although some of the late adverse events we observed might have occurred even in the absence of the investigational agent and with standard therapy, severe late toxicity is relatively uncommon with standard therapy alone, so we believe that a cautious approach is prudent,” Dr. Jagsi and associates wrote.

The study was supported by the Translational Breast Cancer Research Consortium, Breast Cancer Research Foundation, University of Michigan Comprehensive Cancer Center, and Michigan Institute for Clinical and Health Research. Dr. Jagsi reported institutional research support from AbbVie, which donated the veliparib used in the study.

SOURCE: Jagsi R et al. J Clin Oncol. 2018 Mar 20. doi: 10.1200/JCO.2017.77.2665

Voxtalisib, an investigational agent that targets both mTOR and multiple isoforms of PI3K, showed “promising” efficacy with acceptable safety in patients with relapsed or refractory follicular lymphoma (FL), results of a phase 2 trial indicate.

Among 46 patients with FL, the overall response rate was 41.3%, including five (10.9%) complete responses. The median progression-free survival in this group was 58 weeks, reported Jennifer R. Brown, MD, PhD, of the Dana-Farber Cancer Institute in Boston, and her colleagues.

“The observed activity of voxtalisib in relapsed or refractory follicular lymphoma, notable for inducing complete responses in 10.9% of patients, warrants further study,” the investigators wrote in a study published in the Lancet Haematology.

Efficacy of the drug was limited, however, against aggressive malignancies, including mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), or chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Voxtalisib (XL765) is a potent inhibitor of all four class I PI3Ks, as well as a less robust inhibitor of the mammalian target of rapamycin (mTOR). In contrast, idelalisib (Zydelig) – which is approved by the Food and Drug Administration for treatment of relapsed/refractory FL or for CLL, in combination with rituximab – inhibits only the delta isoform of PI3K, and does not have marked anti–mTOR properties.

The investigators conducted an open-label, nonrandomized trial of voxtalisib in 30 centers in the United States, Belgium, France, Germany, the Netherlands, and Australia.

Adults 18 years or older with relapsed or refractory MCL, FL, DLBCL or CLL/SLL with Eastern Cooperative Oncology Group performance status of 2 or less were enrolled. All patients received voxtalisib 50 mg orally twice daily in 28-day continuous dosing cycles until progression or unacceptable toxicity.

All patients who received more the 4 weeks of treatment and had both a baseline and one or more on-treatment tumor assessments were included in the efficacy analysis. Patients with lymphoma had received a median of three prior lines of therapy, and those with CLL had received a median of four prior lines.

The overall response rate in the entire study population was 18.3% (30 patients), including 22 partial and 8 complete responses. ORR rates were as follows:

• FL: 41.3% (19 of 46 patients).
• MCL: 11.9% (5 of 42 patients).
• DLBCL: 4.9% (2 of 41 patients).
• CLL/SLL: 11.4% (4 of 35 patients).

The safety analysis, which included all 167 patients enrolled, was consistent with that of previous studies of voxtalisib, the investigators said. The most frequently reported adverse events of any grade or type were diarrhea in 35% of patients, fatigue in 32%, nausea in 27%, pyrexia in 26%, cough 24%, and decreased appetite in 21%.

Grade 3 or greater adverse events include anemia in 12%, and pneumonia and thrombocytopenia in 8% each. Slightly more than half of all patients (58.1%) had a serious adverse event.

The investigators noted that voxtalisib’s short plasma half-life may explain the drug’s lack of efficacy against the aggressive lymphomas and CLL/SLL. Longer-acting formulations of the drug or more frequent dosing might address this problem, although the latter solution could be challenging for patients to follow, the investigators acknowledged.

In light of the results, no further studies of voxtalisib in CLL are planned, thought investigation of the drug alone or in combination with chemoimmunotherapy is warranted for patients with follicular lymphoma, the investigators wrote.

The study was funded by Sanofi. Dr. Brown reported consulting for Janssen, Gilead, Celgene, Sun BioPharma, Novartis, AbbVie, Pfizer, AstraZeneca, Astellas, RedX, Pharmacyclics, Genentech/Roche, Verastem, and TG Therapeutics, and grants from Gilead and Sun BioPharma.

SOURCE: Brown J et al. Lancet Haematol. 2018 Mar 14. doi: 10.1016/S2352-3026(18)30030-9.
 

Voxtalisib, an investigational agent that targets both mTOR and multiple isoforms of PI3K, showed “promising” efficacy with acceptable safety in patients with relapsed or refractory follicular lymphoma (FL), results of a phase 2 trial indicate.

Among 46 patients with FL, the overall response rate was 41.3%, including five (10.9%) complete responses. The median progression-free survival in this group was 58 weeks, reported Jennifer R. Brown, MD, PhD, of the Dana-Farber Cancer Institute in Boston, and her colleagues.

“The observed activity of voxtalisib in relapsed or refractory follicular lymphoma, notable for inducing complete responses in 10.9% of patients, warrants further study,” the investigators wrote in a study published in the Lancet Haematology.

Efficacy of the drug was limited, however, against aggressive malignancies, including mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), or chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Voxtalisib (XL765) is a potent inhibitor of all four class I PI3Ks, as well as a less robust inhibitor of the mammalian target of rapamycin (mTOR). In contrast, idelalisib (Zydelig) – which is approved by the Food and Drug Administration for treatment of relapsed/refractory FL or for CLL, in combination with rituximab – inhibits only the delta isoform of PI3K, and does not have marked anti–mTOR properties.

The investigators conducted an open-label, nonrandomized trial of voxtalisib in 30 centers in the United States, Belgium, France, Germany, the Netherlands, and Australia.

Adults 18 years or older with relapsed or refractory MCL, FL, DLBCL or CLL/SLL with Eastern Cooperative Oncology Group performance status of 2 or less were enrolled. All patients received voxtalisib 50 mg orally twice daily in 28-day continuous dosing cycles until progression or unacceptable toxicity.

All patients who received more the 4 weeks of treatment and had both a baseline and one or more on-treatment tumor assessments were included in the efficacy analysis. Patients with lymphoma had received a median of three prior lines of therapy, and those with CLL had received a median of four prior lines.

The overall response rate in the entire study population was 18.3% (30 patients), including 22 partial and 8 complete responses. ORR rates were as follows:

• FL: 41.3% (19 of 46 patients).
• MCL: 11.9% (5 of 42 patients).
• DLBCL: 4.9% (2 of 41 patients).
• CLL/SLL: 11.4% (4 of 35 patients).

The safety analysis, which included all 167 patients enrolled, was consistent with that of previous studies of voxtalisib, the investigators said. The most frequently reported adverse events of any grade or type were diarrhea in 35% of patients, fatigue in 32%, nausea in 27%, pyrexia in 26%, cough 24%, and decreased appetite in 21%.

Grade 3 or greater adverse events include anemia in 12%, and pneumonia and thrombocytopenia in 8% each. Slightly more than half of all patients (58.1%) had a serious adverse event.

The investigators noted that voxtalisib’s short plasma half-life may explain the drug’s lack of efficacy against the aggressive lymphomas and CLL/SLL. Longer-acting formulations of the drug or more frequent dosing might address this problem, although the latter solution could be challenging for patients to follow, the investigators acknowledged.

In light of the results, no further studies of voxtalisib in CLL are planned, thought investigation of the drug alone or in combination with chemoimmunotherapy is warranted for patients with follicular lymphoma, the investigators wrote.

The study was funded by Sanofi. Dr. Brown reported consulting for Janssen, Gilead, Celgene, Sun BioPharma, Novartis, AbbVie, Pfizer, AstraZeneca, Astellas, RedX, Pharmacyclics, Genentech/Roche, Verastem, and TG Therapeutics, and grants from Gilead and Sun BioPharma.

SOURCE: Brown J et al. Lancet Haematol. 2018 Mar 14. doi: 10.1016/S2352-3026(18)30030-9.
 

Voxtalisib, an investigational agent that targets both mTOR and multiple isoforms of PI3K, showed “promising” efficacy with acceptable safety in patients with relapsed or refractory follicular lymphoma (FL), results of a phase 2 trial indicate.

Among 46 patients with FL, the overall response rate was 41.3%, including five (10.9%) complete responses. The median progression-free survival in this group was 58 weeks, reported Jennifer R. Brown, MD, PhD, of the Dana-Farber Cancer Institute in Boston, and her colleagues.

“The observed activity of voxtalisib in relapsed or refractory follicular lymphoma, notable for inducing complete responses in 10.9% of patients, warrants further study,” the investigators wrote in a study published in the Lancet Haematology.

Efficacy of the drug was limited, however, against aggressive malignancies, including mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), or chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Voxtalisib (XL765) is a potent inhibitor of all four class I PI3Ks, as well as a less robust inhibitor of the mammalian target of rapamycin (mTOR). In contrast, idelalisib (Zydelig) – which is approved by the Food and Drug Administration for treatment of relapsed/refractory FL or for CLL, in combination with rituximab – inhibits only the delta isoform of PI3K, and does not have marked anti–mTOR properties.

The investigators conducted an open-label, nonrandomized trial of voxtalisib in 30 centers in the United States, Belgium, France, Germany, the Netherlands, and Australia.

Adults 18 years or older with relapsed or refractory MCL, FL, DLBCL or CLL/SLL with Eastern Cooperative Oncology Group performance status of 2 or less were enrolled. All patients received voxtalisib 50 mg orally twice daily in 28-day continuous dosing cycles until progression or unacceptable toxicity.

All patients who received more the 4 weeks of treatment and had both a baseline and one or more on-treatment tumor assessments were included in the efficacy analysis. Patients with lymphoma had received a median of three prior lines of therapy, and those with CLL had received a median of four prior lines.

The overall response rate in the entire study population was 18.3% (30 patients), including 22 partial and 8 complete responses. ORR rates were as follows:

• FL: 41.3% (19 of 46 patients).
• MCL: 11.9% (5 of 42 patients).
• DLBCL: 4.9% (2 of 41 patients).
• CLL/SLL: 11.4% (4 of 35 patients).

The safety analysis, which included all 167 patients enrolled, was consistent with that of previous studies of voxtalisib, the investigators said. The most frequently reported adverse events of any grade or type were diarrhea in 35% of patients, fatigue in 32%, nausea in 27%, pyrexia in 26%, cough 24%, and decreased appetite in 21%.

Grade 3 or greater adverse events include anemia in 12%, and pneumonia and thrombocytopenia in 8% each. Slightly more than half of all patients (58.1%) had a serious adverse event.

The investigators noted that voxtalisib’s short plasma half-life may explain the drug’s lack of efficacy against the aggressive lymphomas and CLL/SLL. Longer-acting formulations of the drug or more frequent dosing might address this problem, although the latter solution could be challenging for patients to follow, the investigators acknowledged.

In light of the results, no further studies of voxtalisib in CLL are planned, thought investigation of the drug alone or in combination with chemoimmunotherapy is warranted for patients with follicular lymphoma, the investigators wrote.

The study was funded by Sanofi. Dr. Brown reported consulting for Janssen, Gilead, Celgene, Sun BioPharma, Novartis, AbbVie, Pfizer, AstraZeneca, Astellas, RedX, Pharmacyclics, Genentech/Roche, Verastem, and TG Therapeutics, and grants from Gilead and Sun BioPharma.

SOURCE: Brown J et al. Lancet Haematol. 2018 Mar 14. doi: 10.1016/S2352-3026(18)30030-9.
 

Among men younger than 65 with prostate cancer, proton beam radiotherapy (PBT) was associated with significantly lower rates of urinary toxicities than was intensity-modulated radiotherapy (IMRT), but this safety advantage came at the cost of nearly $60,000 extra per patient, results of an insurance claims study show.

The rate of a composite of urinary toxicities at 2 years among 693 men treated with PBT was 33%, compared with 42% for 3,465 men matched by propensity score who were treated with IMRT. Respective rates of erectile dysfunction were 21% vs. 28%. The mean cost for PBT, however, was nearly double that for IMRT, reported Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues.

Although PBT was better at sparing patients from urinary toxicities, it was associated with increased bowel toxicities, and a second comparison of IMRT with stereotactic body radiotherapy (SBRT) showed that SBRT, while slightly cheaper than IMRT, was associated with modest increases in some urinary toxicities, the researchers reported in a study published online in the Journal of Clinical Oncology.

“These key findings, coupled with the real-world private insurance cost reported herein, will be useful for patients selecting the most appropriate treatment and for researchers designing cost-effectiveness models to guide treatment decisions in prostate cancer,” they wrote.

The investigators combed through the MarketScan Commercial Claims and Encounters database to identify men who underwent radiation therapy for prostate cancer between 2008 and 2015. They used propensity-score matching, a technique designed to even out potential confounding factors, to compare those treated with IMRT with others treated with PBT or SBRT.

As noted, PBT was associated with significantly lower urinary toxicities and erectile dysfunction compared with IMRT (P less than .001 for each comparison), but with a higher rate of bowel toxicities at 2 years (20% vs. 15%, P = .02).

The mean cost per patient in 2015 dollars for PBT was $115,501, compared with $59,012 for IMRT.

SOURCE: Smith BD et al. J Clin Oncol. 2018 Mar 21. doi: 10.1200/JCO.2017.75.5371.

Among men younger than 65 with prostate cancer, proton beam radiotherapy (PBT) was associated with significantly lower rates of urinary toxicities than was intensity-modulated radiotherapy (IMRT), but this safety advantage came at the cost of nearly $60,000 extra per patient, results of an insurance claims study show.

The rate of a composite of urinary toxicities at 2 years among 693 men treated with PBT was 33%, compared with 42% for 3,465 men matched by propensity score who were treated with IMRT. Respective rates of erectile dysfunction were 21% vs. 28%. The mean cost for PBT, however, was nearly double that for IMRT, reported Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues.

Although PBT was better at sparing patients from urinary toxicities, it was associated with increased bowel toxicities, and a second comparison of IMRT with stereotactic body radiotherapy (SBRT) showed that SBRT, while slightly cheaper than IMRT, was associated with modest increases in some urinary toxicities, the researchers reported in a study published online in the Journal of Clinical Oncology.

“These key findings, coupled with the real-world private insurance cost reported herein, will be useful for patients selecting the most appropriate treatment and for researchers designing cost-effectiveness models to guide treatment decisions in prostate cancer,” they wrote.

The investigators combed through the MarketScan Commercial Claims and Encounters database to identify men who underwent radiation therapy for prostate cancer between 2008 and 2015. They used propensity-score matching, a technique designed to even out potential confounding factors, to compare those treated with IMRT with others treated with PBT or SBRT.

As noted, PBT was associated with significantly lower urinary toxicities and erectile dysfunction compared with IMRT (P less than .001 for each comparison), but with a higher rate of bowel toxicities at 2 years (20% vs. 15%, P = .02).

The mean cost per patient in 2015 dollars for PBT was $115,501, compared with $59,012 for IMRT.

SOURCE: Smith BD et al. J Clin Oncol. 2018 Mar 21. doi: 10.1200/JCO.2017.75.5371.

Among men younger than 65 with prostate cancer, proton beam radiotherapy (PBT) was associated with significantly lower rates of urinary toxicities than was intensity-modulated radiotherapy (IMRT), but this safety advantage came at the cost of nearly $60,000 extra per patient, results of an insurance claims study show.

The rate of a composite of urinary toxicities at 2 years among 693 men treated with PBT was 33%, compared with 42% for 3,465 men matched by propensity score who were treated with IMRT. Respective rates of erectile dysfunction were 21% vs. 28%. The mean cost for PBT, however, was nearly double that for IMRT, reported Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues.

Although PBT was better at sparing patients from urinary toxicities, it was associated with increased bowel toxicities, and a second comparison of IMRT with stereotactic body radiotherapy (SBRT) showed that SBRT, while slightly cheaper than IMRT, was associated with modest increases in some urinary toxicities, the researchers reported in a study published online in the Journal of Clinical Oncology.

“These key findings, coupled with the real-world private insurance cost reported herein, will be useful for patients selecting the most appropriate treatment and for researchers designing cost-effectiveness models to guide treatment decisions in prostate cancer,” they wrote.

The investigators combed through the MarketScan Commercial Claims and Encounters database to identify men who underwent radiation therapy for prostate cancer between 2008 and 2015. They used propensity-score matching, a technique designed to even out potential confounding factors, to compare those treated with IMRT with others treated with PBT or SBRT.

As noted, PBT was associated with significantly lower urinary toxicities and erectile dysfunction compared with IMRT (P less than .001 for each comparison), but with a higher rate of bowel toxicities at 2 years (20% vs. 15%, P = .02).

The mean cost per patient in 2015 dollars for PBT was $115,501, compared with $59,012 for IMRT.

SOURCE: Smith BD et al. J Clin Oncol. 2018 Mar 21. doi: 10.1200/JCO.2017.75.5371.

BOSTON – Bacterial pneumonia, herpes zoster, and thrombocytopenia in adults of any age could be signs of a possible undiagnosed HIV infection and should trigger HIV testing, investigators in a study of aging veterans contend.

Among adults younger than age 60 years, findings of anemia and/or lymphocytopenia also should trigger HIV testing, said Amy C. Justice, MD, PhD, from the Yale School of Public Health, New Haven, Conn.

Neil Osterweil/MDedge News

SOURCE: Justice AC et al. 2018 CROI, Abstract 92

BOSTON – Bacterial pneumonia, herpes zoster, and thrombocytopenia in adults of any age could be signs of a possible undiagnosed HIV infection and should trigger HIV testing, investigators in a study of aging veterans contend.

Among adults younger than age 60 years, findings of anemia and/or lymphocytopenia also should trigger HIV testing, said Amy C. Justice, MD, PhD, from the Yale School of Public Health, New Haven, Conn.

Neil Osterweil/MDedge News

SOURCE: Justice AC et al. 2018 CROI, Abstract 92

BOSTON – Bacterial pneumonia, herpes zoster, and thrombocytopenia in adults of any age could be signs of a possible undiagnosed HIV infection and should trigger HIV testing, investigators in a study of aging veterans contend.

Among adults younger than age 60 years, findings of anemia and/or lymphocytopenia also should trigger HIV testing, said Amy C. Justice, MD, PhD, from the Yale School of Public Health, New Haven, Conn.

Neil Osterweil/MDedge News

SOURCE: Justice AC et al. 2018 CROI, Abstract 92

BOSTON – In San Francisco, a citywide program to get all persons with newly diagnosed HIV infections linked to care within 5 working days cut the time to first virologic suppression by more than half and reduced the median time from initiation of care to antiretroviral therapy from nearly 4 weeks to just 1 day, an infectious disease specialist reported.

“We saw significant improvements in time to ART [antiretroviral therapy] initiation and time to first virologic suppression in traditionally vulnerable populations, including racial and ethnic minorities and the homeless. However, disparities remain in some groups,” Oliver Bacon, MD, MPH, of the University of California, San Francisco, and the San Francisco Department of Public Health, said at the Conference on Retroviruses and Opportunistic Infections.

The investigators identified HIV clinics using HIV surveillance data, and trained providers on RAPID procedures with both in-service training and individual provider detailing.

Providers and clinics that agreed to join the program were added to a RAPID provider directory, which was then given to linkage navigators that could use it to identify the optimal HIV clinic for each newly diagnosed patient, according to insurance coverage and psychosocial needs.

The full protocol and RAPID detailing brochure also were made available to clinicians at a website and were distributed at open quarterly consortium meetings.

Dr. Bacon presented HIV case registry data on care outcomes from 2013 to 2016.

In 2013, 93% of all new HIV cases linked to care; in 2016, 97% linked. The proportion of newly diagnosed persons who started on ART also improved, from 78% in 2013 to 81% in 2016. In addition, the proportion of patients who both linked to care within 5 days and were started on ART within 1 day rose from 6% in 2013 to 30% by 2016.

Similar improvements were seen in median time from diagnosis to care, from 8 days in 2013 to 5 in 2016 (–38%); time from the first care visit to ART initiation from 27 days to 1 day, respectively (–96%); time from ART initiation to virologic load below 200 copies/mL from 70 to 38 days (–46%), and time from diagnosis to virologic load below 200 from 134 to 61 days (–54%).

Time from diagnosis to first care visit decreased significantly for males, whites, Hispanics, youth aged 13-29 years, and for those with housing; time from ART to virologic suppression decreased significantly for males, those under age 40 years, whites, Hispanics, Asian/Pacific Islanders, and for those with housing.

It is important to note that 16% of persons diagnosed with HIV in 2016 had not started on ART. “We found no notable sociodemographic differences versus the ART starters, although we did not look at mental illness [or] ... substance use,” Dr. Bacon said.

He acknowledged that the analysis did not address the important question of durability of virologic suppression.

The San Francisco Getting to Zero Consortium is sponsored by Gilead, Janssen, Bristol-Myers Squibb, the City of San Francisco, and by Will Hagerty. Dr. Bacon reported no conflicts of interest to disclose.

SOURCE: Buchbinder SP et al. CROI 2018, Abstract 87.

BOSTON – In San Francisco, a citywide program to get all persons with newly diagnosed HIV infections linked to care within 5 working days cut the time to first virologic suppression by more than half and reduced the median time from initiation of care to antiretroviral therapy from nearly 4 weeks to just 1 day, an infectious disease specialist reported.

“We saw significant improvements in time to ART [antiretroviral therapy] initiation and time to first virologic suppression in traditionally vulnerable populations, including racial and ethnic minorities and the homeless. However, disparities remain in some groups,” Oliver Bacon, MD, MPH, of the University of California, San Francisco, and the San Francisco Department of Public Health, said at the Conference on Retroviruses and Opportunistic Infections.

The investigators identified HIV clinics using HIV surveillance data, and trained providers on RAPID procedures with both in-service training and individual provider detailing.

Providers and clinics that agreed to join the program were added to a RAPID provider directory, which was then given to linkage navigators that could use it to identify the optimal HIV clinic for each newly diagnosed patient, according to insurance coverage and psychosocial needs.

The full protocol and RAPID detailing brochure also were made available to clinicians at a website and were distributed at open quarterly consortium meetings.

Dr. Bacon presented HIV case registry data on care outcomes from 2013 to 2016.

In 2013, 93% of all new HIV cases linked to care; in 2016, 97% linked. The proportion of newly diagnosed persons who started on ART also improved, from 78% in 2013 to 81% in 2016. In addition, the proportion of patients who both linked to care within 5 days and were started on ART within 1 day rose from 6% in 2013 to 30% by 2016.

Similar improvements were seen in median time from diagnosis to care, from 8 days in 2013 to 5 in 2016 (–38%); time from the first care visit to ART initiation from 27 days to 1 day, respectively (–96%); time from ART initiation to virologic load below 200 copies/mL from 70 to 38 days (–46%), and time from diagnosis to virologic load below 200 from 134 to 61 days (–54%).

Time from diagnosis to first care visit decreased significantly for males, whites, Hispanics, youth aged 13-29 years, and for those with housing; time from ART to virologic suppression decreased significantly for males, those under age 40 years, whites, Hispanics, Asian/Pacific Islanders, and for those with housing.

It is important to note that 16% of persons diagnosed with HIV in 2016 had not started on ART. “We found no notable sociodemographic differences versus the ART starters, although we did not look at mental illness [or] ... substance use,” Dr. Bacon said.

He acknowledged that the analysis did not address the important question of durability of virologic suppression.

The San Francisco Getting to Zero Consortium is sponsored by Gilead, Janssen, Bristol-Myers Squibb, the City of San Francisco, and by Will Hagerty. Dr. Bacon reported no conflicts of interest to disclose.

SOURCE: Buchbinder SP et al. CROI 2018, Abstract 87.

BOSTON – In San Francisco, a citywide program to get all persons with newly diagnosed HIV infections linked to care within 5 working days cut the time to first virologic suppression by more than half and reduced the median time from initiation of care to antiretroviral therapy from nearly 4 weeks to just 1 day, an infectious disease specialist reported.

“We saw significant improvements in time to ART [antiretroviral therapy] initiation and time to first virologic suppression in traditionally vulnerable populations, including racial and ethnic minorities and the homeless. However, disparities remain in some groups,” Oliver Bacon, MD, MPH, of the University of California, San Francisco, and the San Francisco Department of Public Health, said at the Conference on Retroviruses and Opportunistic Infections.

The investigators identified HIV clinics using HIV surveillance data, and trained providers on RAPID procedures with both in-service training and individual provider detailing.

Providers and clinics that agreed to join the program were added to a RAPID provider directory, which was then given to linkage navigators that could use it to identify the optimal HIV clinic for each newly diagnosed patient, according to insurance coverage and psychosocial needs.

The full protocol and RAPID detailing brochure also were made available to clinicians at a website and were distributed at open quarterly consortium meetings.

Dr. Bacon presented HIV case registry data on care outcomes from 2013 to 2016.

In 2013, 93% of all new HIV cases linked to care; in 2016, 97% linked. The proportion of newly diagnosed persons who started on ART also improved, from 78% in 2013 to 81% in 2016. In addition, the proportion of patients who both linked to care within 5 days and were started on ART within 1 day rose from 6% in 2013 to 30% by 2016.

Similar improvements were seen in median time from diagnosis to care, from 8 days in 2013 to 5 in 2016 (–38%); time from the first care visit to ART initiation from 27 days to 1 day, respectively (–96%); time from ART initiation to virologic load below 200 copies/mL from 70 to 38 days (–46%), and time from diagnosis to virologic load below 200 from 134 to 61 days (–54%).

Time from diagnosis to first care visit decreased significantly for males, whites, Hispanics, youth aged 13-29 years, and for those with housing; time from ART to virologic suppression decreased significantly for males, those under age 40 years, whites, Hispanics, Asian/Pacific Islanders, and for those with housing.

It is important to note that 16% of persons diagnosed with HIV in 2016 had not started on ART. “We found no notable sociodemographic differences versus the ART starters, although we did not look at mental illness [or] ... substance use,” Dr. Bacon said.

He acknowledged that the analysis did not address the important question of durability of virologic suppression.

The San Francisco Getting to Zero Consortium is sponsored by Gilead, Janssen, Bristol-Myers Squibb, the City of San Francisco, and by Will Hagerty. Dr. Bacon reported no conflicts of interest to disclose.

SOURCE: Buchbinder SP et al. CROI 2018, Abstract 87.

BOSTON – In antiretroviral therapy–naive patients with HIV and tuberculosis coinfection, a combination of dolutegravir-based ART and rifampin-based TB therapy was associated with good efficacy and immunological responses through at least 24 weeks, investigators reported.

Dolutegravir-based ART appeared to be comparable to efavirenz-based therapy at viral suppression with a similar safety profile, although the trial was not powered for head-to-head comparison, said Kelly Dooley, MD, of Johns Hopkins University, Baltimore.

“We know that rifampin reduces concentrations of dolutegravir substantially, but that drug interaction can be mitigated by increasing the dose of dolutegravir to twice daily. That information was from a healthy volunteer trial, so we thought it would be important to test HIV/TB cotreatment among patients who have both infections,” she said at the Conference on Retroviruses and Opportunistic Infections.

Dr. Dooley and her colleagues looked at dolutegravir or efavirenz plus rifampin-based TB therapy in the INSPIRING trial.

imnews@frontlinemedcom.com

SOURCE: Dooley K et al. Abstract 33.

BOSTON – In antiretroviral therapy–naive patients with HIV and tuberculosis coinfection, a combination of dolutegravir-based ART and rifampin-based TB therapy was associated with good efficacy and immunological responses through at least 24 weeks, investigators reported.

Dolutegravir-based ART appeared to be comparable to efavirenz-based therapy at viral suppression with a similar safety profile, although the trial was not powered for head-to-head comparison, said Kelly Dooley, MD, of Johns Hopkins University, Baltimore.

“We know that rifampin reduces concentrations of dolutegravir substantially, but that drug interaction can be mitigated by increasing the dose of dolutegravir to twice daily. That information was from a healthy volunteer trial, so we thought it would be important to test HIV/TB cotreatment among patients who have both infections,” she said at the Conference on Retroviruses and Opportunistic Infections.

Dr. Dooley and her colleagues looked at dolutegravir or efavirenz plus rifampin-based TB therapy in the INSPIRING trial.

imnews@frontlinemedcom.com

SOURCE: Dooley K et al. Abstract 33.

BOSTON – In antiretroviral therapy–naive patients with HIV and tuberculosis coinfection, a combination of dolutegravir-based ART and rifampin-based TB therapy was associated with good efficacy and immunological responses through at least 24 weeks, investigators reported.

Dolutegravir-based ART appeared to be comparable to efavirenz-based therapy at viral suppression with a similar safety profile, although the trial was not powered for head-to-head comparison, said Kelly Dooley, MD, of Johns Hopkins University, Baltimore.

“We know that rifampin reduces concentrations of dolutegravir substantially, but that drug interaction can be mitigated by increasing the dose of dolutegravir to twice daily. That information was from a healthy volunteer trial, so we thought it would be important to test HIV/TB cotreatment among patients who have both infections,” she said at the Conference on Retroviruses and Opportunistic Infections.

Dr. Dooley and her colleagues looked at dolutegravir or efavirenz plus rifampin-based TB therapy in the INSPIRING trial.

imnews@frontlinemedcom.com

SOURCE: Dooley K et al. Abstract 33.