{"id":35794,"date":"2019-03-12T11:43:38","date_gmt":"2019-03-12T11:43:38","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=35794"},"modified":"2019-03-12T15:36:24","modified_gmt":"2019-03-12T15:36:24","slug":"faster-viral-suppression-in-women-starting-dolutegravir-late-in-pregnancy-results-from-dolphin","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/35794","title":{"rendered":"Dolutegravir suppresses viral load faster than efavirenz in late pregnancy: results from DolPHIN-2"},"content":{"rendered":"

\"\"Polly Clayden, HIV i-Base<\/strong><\/p>\n

Women living with HIV starting dolutegravir (DTG)-based ART after presenting in late pregnancy achieved more rapid virological suppression before delivery than those who started with an efavirenz (EFV)-based regimen \u2013 according to findings from the DolPHIN-2 study, shown at CROI 2019.<\/strong><\/p>\n

But, late presentation in pregnancy is associated with poor outcomes despite ART and regardless of ART regimen.<\/p>\n

DolPHIN-2 (NCT03249181) is an open label study, randomising pregnant women from Uganda and South Africa starting ART from 28 weeks\u2019 gestation to DTG vs EFV plus 2NRTIs.<\/p>\n

The primary endpoint is viral load <50 copies\/mL at delivery (up to 14 days postpartum) for efficacy, and drug-related adverse events in mothers and infants.<\/p>\n

Professor Saye Khoo from the University of Liverpool presented data on behalf of the study group.<\/p>\n

All 268 randomised mothers were included in the safety and 237 (122 DTG, 115 EFV) in the efficacy analyses. Data were censored 31 January 2019.<\/p>\n

Baseline characteristics were similar between arms: median maternal age was 28 years; viral load 4.5 log10 copies\/mL, CD4 count 446 cells\/mm3 and gestation 31 weeks.<\/p>\n

Viral load was measured at baseline, 1 week and 4 weeks after starting ART, then at 36 weeks\u2019 gestation and delivery, and 6 weeks postpartum.<\/p>\n

Median time on ART at delivery was 55 days (IQR 33\u201377): DTG 52 days (IQR 30\u201374) vs EFV 59 (IQR 38\u201382).<\/p>\n

By ITT analysis, viral load <50 copies\/mL at delivery \u2028was significantly higher with DTG (90\/122, 73.8%) vs EFV (49\/115, 42.6%): RR 1.66 (95% CI 1.32 to 2.08), p<0.0001. Viral load <1000 copies\/mL was also higher with DTG (113\/122, 92.6%) vs EFV (95\/115, 82.6%): RR 1.11 (95% CI 1.00 to 1.23), p=0.05.<\/p>\n

There were three vertical transmissions \u2013 all in the DTG arm. Mothers had received 35, 32 and 24 days of ART pre-delivery, which they started at respectively 32, 32 and 30 weeks\u2019 gestation. Their respective infants had 4, 3 and 2 positive PCRs with the first at 5, 3 and 11 days after delivery. Maternal viral load at delivery was 29, 20 and 200 copies\/mL for the respective cases.\u00a0 All four were judged likely to be in-utero transmissions.<\/p>\n

DTG was well-tolerated in pregnancy with no differences with EFV in frequency or organ class of severe adverse events.<\/p>\n

There were four stillbirths \u2013 all in the DTG arm. These were judged not related or unlikely to be related to ART or maternal IRIS.<\/p>\n

Among 242 evaluable live births, median gestation at delivery was 39.9 weeks in both arms with similar rates of preterm and very preterm deliveries: 16% and 5% respectively overall.<\/p>\n

About half of the infants had at least one SAE. There were 7 infant deaths (DTG 4 and EFV 3) also judged not related or unlikely to be related to ART or maternal IRIS.<\/p>\n

Overall 38% of infants had congenital, familial and genetic anomalies. But excluding congenital umbilical hernia (29.8%) and birthmark (15.3%) these were in the normal range and there were no neural tube defects.<\/p>\n

In conclusion, DTG achieves faster virological suppression before delivery compared with EFV and is well tolerated.<\/p>\n

The three infant infections were likely to be in-utero transmissions. The four still births in the DTG arm were associated with known risk factors and unlikely to be related to ART.<\/p>\n

Polly Clayden is on the trial steering committee of DolPHIN-2.\u00a0\u00a0\u00a0<\/em><\/p>\n

comment<\/h3>\n

As previously reported, HIV positive women who start ART in late pregnancy are a vulnerable group with a higher risk of adverse outcomes and vertical transmission of HIV than those who start earlier.\u00a0<\/strong><\/p>\n

Infant deaths, stillbirths and infant infections seen in DolPHIN-2 corroborate this. Such women are difficult to reach (and to recruit in to studies) but efforts must be made to ensure that they receive care and treatment earlier in pregnancy.<\/strong><\/p>\n

Mothers and infants in DolPHIN-2 will be followed to 72 weeks after delivery.<\/strong><\/p>\n

Reference<\/p>\n

Kintu K et al. RCT of dolutegravir vs efavirenz-based therapy initiated in late pregnancy: DolPHIN-2. CROI 2019. Seattle. 4\u20137 March 2019. Oral abstract 40LB.<\/p>\n

http:\/\/www.croiconference.org\/sessions\/rct-dolutegravir-vs-efavirenz-based-therapy-initiated-late-pregnancy-dolphin-2<\/a> (abstract)<\/p>\n","protected":false},"excerpt":{"rendered":"

Polly Clayden, HIV i-Base Women living with HIV starting dolutegravir (DTG)-based ART after presenting in late pregnancy achieved more rapid virological suppression before delivery than those who started with an efavirenz (EFV)-based regimen \u2013 according to findings from the DolPHIN-2 …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,35],"tags":[264],"class_list":["post-35794","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-pmtct-and-maternal-health","tag-croi-2019"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/35794","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=35794"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/35794\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=35794"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=35794"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=35794"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}