key: cord-0699144-8qkj96ii
authors: Goga, Ameena E; Van de Perre, Philippe; Ngandu, Nobubelo; Nagot, Nicolas; Abrams, Elaine J; Moodley, Dhayendre; King, Rachel; Molès, Jean-Pierre; Chirinda, Witness; Scarlatti, Gabriella; Tylleskär, Thorkild; Sherman, Gayle G; Pillay, Yogan; Dabis, François; Gray, Glenda
title: Eliminating HIV transmission through breast milk from women taking antiretroviral drugs
date: 2021-09-29
journal: BMJ
DOI: 10.1136/bmj.n1697
sha: 0429f64d5ae90e33b5211fd296c57225497d8698
doc_id: 699144
cord_uid: 8qkj96ii

Ameena Goga and colleagues argue that frequent testing of maternal viral load is needed to eliminate HIV transmission through breast milk in low and middle income settings

Pregnant HIV-1 infected women with CD4+ ≥200 randomly assigned to Trizivir twice daily or Kaletra with Combivir twice daily starting between 26 and 34 weeks' gestation through weaning or 6 months postpartum (whichever occurred first). If CD4+ <200 cells or AIDS lifelong ART started between 18 and 34 weeks' gestation Of 8 infants infected with HIV, two were infected during breastfeeding, at ages 91 and 94 days. Of these 2 infants: • One of these mothers reported ART adherence challenge: her PVL at delivery, 1 month and 3 months was 257, <50 and <50 copies/mL respectively. Her breastmilk VL (BVL) at months 1 and 3 were <50 and <50. • The other mother had a PVL of <50 copies/mL at delivery, months 1 and 3 and a BVL <50 copies/mL at months 1 and 3 Comment: Mothers on ART with suppressed viral loads, who were closely monitored still transmitted HIV to their children postnatally Giuliano et.al. 2 Malawi, Feb 2008 Feb -2009 Observational study of HIVpositive pregnant women attending two antenatal Clinics, Malawi. Women older than 16, naïve to antiretrovirals (with the exception of single-dose nevirapine), willing to breastfeed up to 6 months with no grade 3 or 4 laboratory toxicity and no active tuberculosis were enrolled 8 children became HIV infected: two were detected during month 1, one during month 3, one during month 6 and four during month 12. Plasma VL (PVL) and breastmilk VL (BVL) presented as copies /mL were available for 7 babies, plasma V was consistently less than 67 copies/mL in 4 children. Breastmilk VL was consistently lower than 37 copies/mL in 2 children. Analysis included mothers randomised to 28 weeks of postpartum antiretrovirals with ≥1 plasma or breastmilk specimen AND all mothers who transmitted HIV to their infants from 2 to 28 weeks (n=31) AND 15% of mothers who did not (n=232). Plasma and breastmilk HIV RNA obtained at enrollment, 2, 6, 12, 18, and 24 weeks postpartum. Breastmilk HIV RNA also measured at 4 and 8 weeks postpartum. HIV RNA detected but below quantitation limit were assigned 39 for plasma and 55 for breastmilk. Undetectable RNA concentrations were assigned a value of 20 in plasma and 28 for breastmilk.

Partial and near perfect adherence were associated with a 76% (95% CI 28-92%) and a 62% (95% CI 14-83%) reduction in the odds of having detectable breastmilk VL, respectively compared with poor adherence. • Among 27 HIV infected infants, 1 infant infected at 24 weeks, was born to a mother with undetectable baseline plasma VL, and three high postpartum VL measurements (8,000-108 000 copies/ml (median 20 weeks gestation) from a peri-urban primary care facility, Cape Town, South Africa. ART regimen was Tenofovir 300 mg+emtricitabine /lamivudine 300 mg+efavirenz 600 mg.

(IQR 42-49 days); 25 infants (5%) were tested within 24 h of birth. MTCT was 1.3% (95% CI 0.5-2.6%)=7 infants. Early MTCT (6-weeks post-delivery) differed significantly by maternal plasma VL (P<0.001):

• VL <50: 0.25% (n=1 of 406), • VL 50-1000: 2.0% (n=2 of 102) and

• VL >1000: 8.5% (n=4 of 47) In infants testing positive, pre-ART maternal VL was higher, gestation at ART initiation was later, and duration of maternal ART use before delivery was shorter, compared with infants testing negative.

• One of the 7 transmissions occurred in a mother who previously achieved viral suppression (VS) and then experienced subsequent viraemia around delivery. • Another transmission was observed in a woman who achieved VS soon after initiation and sustained this through pregnancy and delivery; the remaining five transmissions occurred in women who did not achieve VS before delivery Comment: Women with VL <1000 copies/mL accounted for 43% of MTCT. Gill et.al. 5 Kabeho study 600 HIV-positive women with delivery data, enrolled in follow-up (April 2013 -January 2014). The most common regimen was Tenofovir 300 mg+lamivudine 300 mg+efavirenz 600 mg.

• Of the four infants infected with HIV postnatally (detected at 9 or 24 months) one was born to a mother with a VL <1000 at delivery and one to a mother with no VL at delivery. Cohort of 620 ART-eligible pregnant women recruited and initiated in ART at first ANC (median 20 weeks gestation) from a peri-urban primary care facility, Cape Town, South Africa. VL measured at every follow-up: Follow-up schedule:

• <31 weeks at enrolment: 2-weeks later, 34-36 weeks and as soon as possible (asap) after delivery • ≥31 -<36 weeks at enrolment: 34-36 weeks' gestation and asap after delivery • >36 weeks: asap after delivery • • VL at delivery based on first postpartum VL measurement -replaced by last antenatal VL measurement if this was within 14 days of delivery and postpartum measurement was more than 14 days after delivery.

Viral suppression (VS) defined as ≤50 copies/mL. Median time to plasma VL <1000 copies/mL or VS, respectively was: • 24 days, increasing to 76 days (≈2.5 months) if plasma VL >5.0 log10 copies/mL at ART initiation (P<0.001). • 94 days increasing to 131 days (≈4.5 months) if plasma VL >5.0 log10 copies/mL at initiation (P<0.001). At 8 weeks before delivery: 71% had VL ≤1000 and 48% ≤50 copies/mL By 4 weeks before delivery: 79% had VL ≤1000 and 60% ≤50 copies/mL 477 women achieved VS ≤50 copies/mL before delivery; 40 viraemic episodes (>50 copies/mL) were observed in 27 (6%) women who had viral suppression: 58% of these episodes involved viraemia ≤1000 copies/mL (median 2.1 log10 copies/mL; IQR 1.8-3.6 log10 copies/mL); 44% showed resuppression to ≤50 copies/mL at a subsequent visit. The incidence of viraemic episodes was not associated with pre-ART VL, CD4 cell count or participant demographics At delivery: 91% of women (517/587; 95% CI 89-93%) had VL ≤1000 copies/mL and 73% had VL ≤50 copies/mL (429/587; 95% CI 69-77%). Among the 27% of women (n=158) with VL >50 copies/mL at delivery 19% had achieved VS ≤50copies/mL earlier in pregnancy. In a multivariable model, pre-ART viraemia and gestation at ART initiation remained strongly associated with VS at delivery Probability of VS was predicted as >80% if ART was initiated before 15 weeks, regardless of pre-ART VL, and at pre-ART VL <3.5 log10 copies/mL regardless of gestation. The predicted probability of VS ≤50 copies/mL at delivery decreased to <50% for women initiating ART after 20 weeks' gestation with pre-ART VL >4.0 log copies/mL, and reduced to <10% for women initiating ART after 28 weeks' gestation with pre-ART VL >5.0 log copies/mL. However, this latter sub-group constituted <5% of the overall cohort 523 pregnant/postpartum women on ART ever achieving VL suppression, were followed at 7 days postpartum, six weeks postpartum, then 3 monthly from 3 until 12 months postpartum Postnatally from 7-days to 12 months:

• 70% sustained VL ≤50 copies/mL; • 22% had at least one VL >1000 copies/mL, and 58% of the latter had more than one VL measurement VL >1000 copies/mL. Each additional month postpartum was associated with an 11% (incidence risk ratio 1.11 (95% CI 1.07-1.15) increased incidence of viraemia Gill et.al. 5 Kabeho study: Rwanda, April 2013--January 2014) 600 HIV-positive women on ART with delivery data, enrolled in follow-up.

Maternal VL was evaluated at enrolment within 2 weeks of delivery and 24 months among women who delivered At enrollment: 52.5% had undetectable plasma VL (<20 copies/mL); 84.7% had VL <1000copies/mL At delivery: Prevalence of VL <20 copies/mL was 55.3%; of VL <1000 copies/mL was 88.4%, Among the 70% of women with data at 24 months: VL <20 copies/mL was 78.2% and VL <1000 copies/mL was 91.2% 

Antiretroviral regimens in pregnancy and breast-feeding in Botswana

Maternal antiretroviral therapy for the prevention of mother-to-child transmission of HIV in Malawi: maternal and infant outcomes two years after delivery

BAN study team. Maternal and breastmilk viral load: impacts of adherence on peripartum HIV infections averted-the breastfeeding, antiretrovirals, and nutrition study

HIV viraemia and mother-to-child transmission risk after antiretroviral therapy initiation in pregnancy in Cape Town, South Africa

24-month HIV-free survival among infants born to HIV-positive women enrolled in Option B+ program in Kigali, Rwanda: The Kabeho Study

Low detectable postpartum viral load is associated with HIV transmission in Malawi's prevention of mother-to-child transmission programme

Detectable viral load in late pregnancy among women in the Rwanda option B+ PMTCT program: enrollment results from the Kabeho study

Characterizing Viral Load Burden Among HIV-Infected Women Around the Time of Delivery: Findings From Four Tertiary Obstetric Units in Gauteng, South Africa

Frequency of Viremic Episodes in HIV-Infected Women Initiating Antiretroviral Therapy During Pregnancy: A Cohort Study

CQI-PMTCT study team. HIV viral suppression among pregnant and breastfeeding women in routine care in the Kinshasa province: a baseline evaluation of participants in CQI-PMTCT study

Among the 1623 HIV positive women recruited during pregnancy (54%), 1-3 days post-delivery (23%) or while breastfeeding during well child visits (23%): 62% had VL <1000 copies/mL and 53% had VL <40 copies/mL respectively