Breastfeeding and ART Safety as Prevention of HIV-1 transmission through breastfeeding.
INTRODUCTION to the study on Breastfeeding and the safety of ART.
Well. I had not thought about breastfeeding and the safety of ART until the last Friday or Saturday. Those who live under the effects of methadone, gabapentin, amitril and quetiapine have a very different perception of the passage of time!
Especially because it has neuropathic pain as a "adjunct", and knowing how long something has happened is quite complicated for me. And yet, that does not make me indifferent. Lack of empathy generates psychopaths or people without any sensitivity and, what is worse, generates the impossibility of being, as the North Americans say, on their shoes! In their skin!
And all this because, maybe 40.000 years ago someone came to me, sad (it's the word light that I chose) because I was going to die.
It was not difficult to calm her down. After all, all of us, stellar or not, will die one day, and well, this reference is not without explanation. There remains the quest for consolation, which now does not only go to Joy (joy) and perhaps in one way or another, I can not change scientific facts, some waiting.
And empathy, is something I do not lack, or I would not be mentioned in the UN, in the campaign:
What if it were You?
That, yes, is something!
Let's go to the facts
Modern breastfeeding or breastfeeding and hands living with HIV or AIDS
Substantial progress has been made in preventing perinatal transmission of HIV-1prevent perinatal transmission of HIV in the developing world, but there is still some question as to the relative safety and efficacy of various antiretroviral regimens. Cuba, for example, was the the first country to eradicate vertical transmission - from mother to child. In the Antepartum Component of a large randomized clinical trial from several countries, Promoting Maternal Child Survival in Any Place (PROMISE), we showed that maternal antiretroviral therapy (mART) during pregnancy and intrapartum can reduce perinatal transmission of HIV-1 to -0,5% in sub-Saharan Africa definitions.1
However, exposure to HIV-1 associated with breastfeeding and potential transmission remains babies exposed to HIV who live in places with limited resources. Although guidelines from the World Health Organization (WHO) recommend that all pregnant women infected with HIV-1 start ART throughout their lives, adherence to ART, particularly in the postpartum period, has proven to be a major challenge.
Because the postpartum viral rebound was observed in 31% of women who started ART during pregnancy, who had initial viral suppression and 22% of women who had they suffered the prejudice. ART is detectable at the first prenatal visit.2-4 Thus, evaluating the safety and efficacy of alternative strategies, such as infant prophylaxis, to reduce postnatal infection remains important.5
Prevention of HIV-1 transmission through breastfeeding for Infants Exposed to HIV
Thus, based on previous clinical trial data, the following 2 strategies were shown to be safe and effective in preventing postnatal transmission of HIV-1:
(1) supply of ART for the lactating woman, thus reducing the viral load of breast milk;
or (2) provide daily antiretroviral (ARV) prophylaxis to the infant by maintaining prophylactic blood levels of ARV in children throughout the lifetime risk of HIV-1 transmission.6-13
In previous studies, however, they focused on interventions given only during the first 6 to 12 months of breastfeeding and there were additional late infections related to the transmission of breastfeeding when breastfeeding continued after stopping prophylaxis. And, after prolonged observations, increased morbidity and mortality associated with weaning compared with continued breastfeeding up to the second year of life in infants exposed to HIV-1 were noted.
Therefore, the ever-known metric of prolonged breastfeeding to create stronger adults showed that it was necessary to seek schemes to maintain safe breastfeeding beyond 12 months and interventions were initiated to reduce the transmission of HIV-1 during breastfeeding to reduce disease by HIV and child survival free of it.14-16
The efficacy of prolonged maternal or infant prophylaxis
Some studies have evaluated the safety and efficacy of prolonged maternal or infant prophylaxis, but only up to 12 months.11,12
However, no previous randomized trial directly compared the efficacy and safety of prolonged antiretroviral prophylaxis with maternal ART throughout the duration of breastfeeding until the second year of life.
We report the results of the Postpartum Component of the PROMISE study, which randomized HIV-1-infected women with high CD4 cell count and their HIV-1 uninfected infants at 6-14 days postpartum for mART prophylaxis or nevirapine (iNVP) to prevent transmission of HIV-1 during breastfeeding
Prevention of HIV-1 transmission through breastfeeding: Procedures and Referral to Clinics
Maternal visits occurred at weeks 1 (6-14 days postpartum, entry), 6 and 14 after childbirth, and then every 12 weeks until postpartum 74 week. General medical history and limited physical examination were obtained at each visit. Complete blood count was performed at all visits and chemical safety labs (ALT, aspartate aminotransferase, creatinine, alkaline phosphatase, total bilirubin and albumin) were also obtained, except at week 62.
CD4 cell counts were performed on all visits, except postpartum 6 week.
Pregnancy tests were obtained in case of suspected pregnancy. Babies' visits occurred in the postpartum weeks 1, 6, 10, 14, 18, 22 and 26, then every 12 week to week 98, with a final visit in 104 week.
Children Can Be Born Without HIV. And with some time of Treatment!
History and physical assessment were performed on all visits. HIV-1 NAT, complete blood count and stored plasma were collected in all consultations except 10 week; ALT was obtained at weeks 1 and 6.
For neonates randomized to iNVP, ALT was performed at week 26 and at each 12 week while receiving NVP. An HIV-1 antibody test could replace NAT if the baby was more than 18 months old and had stopped breast-feeding.
Babies diagnosed with HIV infection were referred to the local treatment clinic to initiate HAART; follow-up of the study continued regardless of the state of infection.
Prevention of HIV-1 transmission through breastfeeding: The achievements of these studies on breastfeeding and the safety of ART as a prevention of HIV-1 transmission
The primary efficacy endpoint was confirmed by HIV-1 infant infection, defined as HIV-1-positive NAT from a sample taken at any post-randomization visit, confirmed by HIV-1-positive NAT in a second specimen drawn in a later moment.
Uncertain HIV infection.
Cases of uncertain HIV-1 infection in infants were reviewed, blind to arm assignment, by an independent committee of 4 members who made the definitive determination of the status and timing of HIV-1 infection.
HIV-1 free survival (infant alive and not infected by HIV-1) and infant death were secondary measures of efficacy results.
All HIV-1NATs were performed in laboratories certified by the AIDS Division (DAIDS) Virology Quality Assurance Program.
The DAIDS Table for Adverse Event Severity in Adults and Pediatric, 1.0 version of 2004 (clarification in August of 2009) was used to classify adverse events.19
For women, the primary safety endpoint was a combination of hematological, renal, or hepatic abnormalities of grade 2 or degree ≥3 of adverse events or death, whichever occurs first. (This haunts me)
For children, the primary safety endpoint was a compound of degree ≥3 adverse events or death, which occurred first. Secondary safety outcomes included the individual components of the primary composite outcomes.
Ever! Always Africa !!!!!
Between 6's June 2011 and 1's October 2014, a total of 2431 pairs of mothers and children (including 13 pairs of twins) were enrolled (1220 randomized to mART and 1211 to iNVP) from sites in
- Malawi (32%),
- South Africa (23%),
- Zimbabwe (22%),
- Uganda (16%),
- Zambia (2%),
- Tanzania (2%)
- and India (3%).
Ninety-five percent of the pairs of mothers and offspring in each arm were previously enrolled in the PROMISE Antepartum Component (42% randomized to Maternal ZDV Arm and 53% randomized to Maternal Triple ARV Arm) and 5% were women with late presentation enrolled in childbirth or within 5 days after childbirth.
Almost all (1207,98,9%) of mothers in the mART arm started the mART regimen preferred by the study and almost all (1204,98,9%) of the children in the iNVP arm started daily NVP. A patient flow chart is shown in Supplemental Digital Content, http://links.lww.com/QAI/B102.
Table 1 (I could not use the tables without violating copyright) summarizes the basic characteristics selected from mothers and infants at baseline.
The median time to cessation of breastfeeding was 16 months (70 weeks), with no statistically significant difference between arms (P = 0,70).
The Kaplan-Meier probability estimates for continuous breastfeeding for 6, 9, 12, 18 and 24 months of age were respectively 93,3%, 86,2%, 81,0%, 34,3% and 12,5%.
About copyright in images, I would like to be able to count on a volunteer illustrator for jobs like those in the tables. The pictures on I know, I get my way!
Introductory, I would say, PROMISE study was the first randomized study to conduct a comparative comparison between mART and iNVP for postnatal HIV-1 transmission in up to 18 months of breastfeeding in asymptomatic women with high counts of CD4 who did not meet the treatment criteria at the time of breast-feeding at the time the study was performed.
And even though, even though the cumulative transmission rates of postnatal HIV-1 in the mART and iNVP arms were much smaller than predicted in sample size calculations, this greatly limited the statistical power of the study to detect a difference in risk of transmission between both arms, the results demonstrate that both iNVP regimens were highly effective!
Prevention of HIV-1 transmission through breastfeeding: Survival of 97%!
When I got to this part of the text, still in the English version she came back and with her the pains and the tears. I do not understand and I find it unjustifiable, and this is "only" the first time I play in this topic. Not having reference can not be a justification for disappointments (sic) or misleading communications and considerations!
It takes a complete lack of empathy, maybe even indifference to see yourself in a situation and not look sideways and, seeing that you are not alone and that others are not so well, remain happy!
Lack of empathy generates monstrosities. Emmanuel, by the hands of Chico Xavier, clarifies that "the demons of delusion and delusions are, in short, highly sophisticated intelligences, , which brings us closer to holiness and brings "the rest" (!!!!!) for mercy! Citing vaguely the Christ:
- "Search before" ...
And she is still here, on her mother's lap, dressed in pink, gray eyes for not yet needed and never achieved pigmentation .... Her cry tells me:
And I do not know what to say. Among so many things I had to do that afternoon at Rua Antônio Carlos, Cerqueira César, I stayed to watch and try to mitigate its agony. I knew she would go. I had seen this before, the death in its making, and I would still see it dozens and dozens of times. More than it would be fair for me to have seen .... But…
- "Not to get worse", do not give water ...
How can agony be improved?
- "Wet cotton on your lips"
Where is the mother?
"On the fourth floor."
(The ICU) And the father.
- "He left yesterday! Did you see"! (The guy I would have climbed before, if possible, if I had to hit him before, and he would have fallen into water in very few hours)
And she's gone. Less than 90 days on Earth! Came to the Light to agonize and leave!
And yes, I know, I learned on the phone!
- "All is as God desires"
Not having reference is not the magic formula for those who do not build History to be able to say anything stupid without having to worry about consequences!
But the lack of reference! Just study and research, goodwill and respect.
For the thirty-five million who are no longer here and for another thirty-five million with ambiguous and dubious expectations that serve as living references! For those who took AZT and DDI to survive and often lost their lives. For it is they, as I and so many of us, that we fuck and take in the rai-fi-oiz of green, yellow, blue and white, in the vanguard, so that others today have, as they have, better therapies, with less damage and, for what we're doing |:
- Aging with HIV. We are the first and if I do not speak for all, I speak for myself and DEMAND THIS RESPECT!
Postnatal infections from 12 to 24 months at a rate of 0,6 and 0,9% respectively
With postnatal infection rates of 12 and 24 months of 0,6% and 0,9%, respectively, and high rates of HIV-1 free survival at 24 months (> 97%). The high survival rates below two years (1,7% of infant mortality) were particularly striking in comparison with rates in most places where the study was conducted.24
Two contemporary studies, the ANRS 12174 and the Uganda PROMOTE, showed similar survival rates, but with 50 weeks of follow-up.
ANRS 12174 randomized uninfected HIV-1 infants to LPV / r or 3 TC by discontinuing breast-feeding or 50 weeks.
The free survival of HIV-1 at 50 weeks was of 96% in both arms of the study.11
Women infected with HIV-1 in the PROMOTE study were randomized between 12 and 28 weeks of pregnancy for a regimen based on LPV / r or efavirenz which was continued for 48 weeks of breast-feeding. HIV-1-free infant survival at 8 weeks postpartum was 92,9% in the LPVr arm and 97,2% in the efavirenz arm.12
Rates of HIV-1 transmission in these studies were also low.
In the PROMOTE study, HIV-1 infection occurred during breast-feeding in 1 in the child's LPV / r arm. The infection rates after 50 weeks in the ANRS 12174 study were 1,4% in the arm of the LPV / re 1,5% in the 3 TC arm. To date, there is only one study that compared the efficacy of mART and infant prophylaxis.
Prevention of HIV-1 transmission through Breastfeeding
O Breastfeeding, Antiretroviral and Nutritional Study (BAN) compared a regimen of intrapartum sdNVP plus 7 days of ZDV / 3 TC in all women, followed by a randomization in 1 of 3 groups: extended prophylaxis of mART or daily iNVP prophylaxis given by 7 months of exclusive breastfeeding or no further antiretroviral prophylaxis in mothers or infants.
Although not designed or used to directly compare the efficacy of mART and iNVP, the study results indicated that the mART and iNVP arms were superior to the control arm of 1 week (3%, 1,8% and 6,4% , respectively) at 28 weeks after delivery.10
It should be noted that women in the BAN received only sdNVP and 7 days of ZDV / 3 TC as prophylaxis for perinatal transmission, while 95% of the PROMISE cohort were followed in the antepartum component and received mART or ZDV. In addition, women in the BAN study were enrolled only if the CD4 count was greater than or equal to 200 or 250 cells / mm3 (depending on enrollment time), while women enrolled in the PROMISE cohort had CD4 cell counts ≥350 cells / mm3 (or ≥ the country-specific initial ART threshold if it were> 350 cells / mm3). These underlying differences in subject selection are likely to explain the higher rates of HIV transmission observed in the BAN study.
No safety concerns were observed in the arms of the mART and iNVP study (I.e.
In addition, no safety concerns were observed in the arms of the mART and iNVP study. Less than 1% of women and 2% of children discontinued study regimen due to toxicity. Concerns have been raised about the potential infant toxicity from ingestion of ARVs in the breast milk of mothers receiving ART. Our study found no evidence of increased toxicity rates in infants of mothers receiving tenofovir-based antiretroviral therapy compared to infants whose mothers were not receiving HAART. These data are also reassuring regarding the safety of pre-exposure TDF / FTC prophylaxis for breastfeeding, uninfected women at risk for HIV, and their infants.25-27 Likewise, prolonged use of daily NVP prophylaxis in children not infected with HIV-1 for up to 18 months was not associated with high infant toxicity, including skin and liver toxicity, compared to children who did not receive NVP.
Prevention of HIV-1 transmission through breastfeeding:
The median age of the infant until termination of breastfeeding in the study was 16 months, with 86% of children still not having achieved complete cessation of breastfeeding in 9 months, decreasing to 34% in 18 months. This is longer than what was originally formulated during the design of the study and probably reflects changes in the guidelines on breastfeeding by HIV-1-infected women as well as changing habits among sub-Saharan women during the study. This prolonged duration of breastfeeding puts the baby exposed to HIV-1 at risk of infection if there is inadequate adhesion of ART to the mother.
Approximately 67% of infections occurred after 6 months of life. In my opinion it is beyond inefficient!
E 33% after 12 months of life, with infections continuing to occur in 24 months.
During the randomized PROMISE trial, the WHO guidelines for the prevention of perinatal transmission of HIV-1 were modified in 2013 to recommend maternal ART until at least the duration of breastfeeding.
Current guidelines recommend lifelong ART for all individuals infected with HIV-1, including pregnant and nursing women.17,28 Despite these recommendations, due to problems of postpartum adherence, many women experience rebound viremia, resulting in continuous postnatal transmission.3,4,29 PROMISE data demonstrate that mART and iNVP have similar efficacy and safety profiles up to 24 months of breastfeeding, indicating that although treatment for breastfeeding women is a priority, prolonged use of iNVP is an effective and safe alternative, For example, for women who refuse or do not adhere to ART, have persistent viremia or who temporarily stop ART for toxicity.5
Toxicological Limitations and Prevention of HIV-1 transmission through breastfeeding
However, for women who refuse or do not adhere to ART, there may be similar barriers to the administration of iNVP.
Our data underscore the importance of providing postpartum support to women receiving ART because we observed a continuing risk of postnatal infection during breastfeeding, even when effective interventions were being provided. A variety of approaches will be required to achieve an HIV-1-free generation, including interventions to support ART adherence and postpartum retention in women's care, and to ensure the availability of equally effective and safe infant-prophylaxis alternatives for that Maternal ART may be insufficient to protect the infant.
The PROMISE team recognizes with gratitude the contributions of the mothers and their babies who participated in the study. The team also recognizes the support and donation of study products from pharmaceutical companies Gilead, GSK / Viiv / Healthcare, Abbvie and Boehringer Ingelheim. The authors acknowledge with gratitude the contributions of the study team, site researchers and site team who conducted the study of IMPAACT 1077BF.
Translated and Revised By Cláudio Souza in March 24 of the original 2019 in: