In addition, a study conducted in Africa confirms the recommendation of dolutegravir as a safe and effective treatment for pregnant women with HIV.

 The use of dolutegravir and efavirenz is safe and effective for both pregnant women with HIV and their children, according to data from the DolPHIN-2 trial, presented at the recently held Conference on Retroviruses and Opportunistic Infections (CROI). virtual due to the COVID-19 pandemic.

In 2019, the World Health Organization (WHO) recommended the use of dolutegravir (Tivicay®, also in Triumeq® and Dovato®) as part of antiretroviral treatment for pregnant women with HIV. To date the standard treatment of this population was based on efavirenz (Sustiva® or Stocrin®, also Atripla® and Symfi®).


These new guidelines came to resolve the doubts about whether or not women of childbearing age should take dolutegravir, given that the previous year in the Tsepamo (Botswana) study an increase in the rate of neural tube defects was detected in babies who were exposed. to the drug around the time of conception and the first stages of pregnancy.

The DolPHIN-2 study was designed to compare the efficacy of dolutegravir versus efavirenz in controlling HIV viral load in women who started treatment in late pregnancy. It is important for a woman to reach undetectable viral load as soon as possible to prevent mother-to-child transmission of HIV. CROI's findings had already been reported in last year's CROI, revealing that more women with undetectable viral load at delivery were in the group receiving dolutegravir plus two analog reverse transcriptase inhibitors nucleoside / nucleotide (ITIN) than in the group assigned to receive efavirenz. Also, the number of babies who acquired HIV was higher in the efavirenz arm than in the dolutegravir arm.

In relation to this issue, the US President's Emergency Plan to Palliate AIDS (PEPFAR) indicated in 2019 in Medscape Medical News that 1 million people abandoned treatment with efavirenz due to different side effects such as fatigue or depression. This could make it difficult to maintain an undetectable viral load and, together with the possibility of acquiring HIV if not, makes the postpartum period difficult for women.

In this edition of the conference, the results of the DolPHIN-2 study up to 18 months after delivery have been presented, from a cohort of 250 women with HIV in Uganda and South Africa who breastfed their babies for six months without the use of formula and then continued non-exclusive breastfeeding for six to one year. The mean age of the participants was 28 years old (18 years old being the minimum to enter the study). The women entered the trial when they were already, on median, in their 31st week of pregnancy, that is, in the third trimester of gestation. Only for 12% it was their first pregnancy while the rest had given birth to an average of two children previously.

At the time of entry into the study, none of the participants was receiving treatment for their HIV infection and their median CD4 count was 449 cells / mm3. The mean viral load found in this study was much higher than 1000 copies / mL, a threshold below which the risk of vertical transmission of HIV decreases significantly.

The women were randomized to receive antiretroviral therapy containing dolutegravir or efavirenz. The researchers found that women in the first group reached the viral load threshold of 1000 copies / mL in one week and an undetectable level in a median of 4.14 weeks. In the efavirenz arm, it took the women 3.71 weeks to drop their viral load below 1000 copies / mL and 12 weeks to reach undetectability. In other words, women taking dolutegravir were 83% faster to reach a viral load less than 100 copies / mL and 93% faster to have an undetectable viral load than women taking an efavirenz-based treatment.

Although both regimens were effective in preventing viral load rebound, in the arm of women on efavirenz there were eight women who experienced treatment failure, compared with three for dolutegravir. Of this total of 11 women, six did not have an undetectable viral load at week 24 and five saw their viral load rise again after reaching undetectability. On the other hand, at week 72, the tolerance profile of the two drugs was good. In total, 57 adverse events were recorded, 49 of them serious, although only 3% of them were drug-related, three in the dolutegravir arm and five in the efavirenz arm.

Fifty-six percent of babies (136 out of 242) experienced some side effect and one in four of them was serious, the most prominent being umbilical hernias and birthmarks. However, in none of the cases were they linked to antiretrovirals. Eleven babies died, eight of them in the dolutegravir arm.

There was only one case of HIV infection in a baby whose mother was taking efavirenz. The baby tested positive at the end of the study at 72 weeks, but had previously tested negative at birth, at six weeks and at 12 (did not make the visits scheduled at 24 and 48 weeks). Even so, the mother was constantly followed up and it is known that she had a low (although detectable) level of viral load at the time of delivery (126 copies / mL) and at week 12 (69 copies / mL). The remaining weeks she did maintain an undetectable level of undetectable viral load, except at week 24, when there was a temporary rebound in viral load (blip), reaching 126 copies / mL.

Regarding this case, the team of researchers has reported that, although the mother was below the aforementioned limit of 1000 copies / mL, the viremia of mother and child presents a similar pattern of drug resistance, which would point to that the baby's HIV is indeed linked to that of the mother, although a more in-depth phylogenetic analysis has not yet been carried out to confirm this.

In their conclusions, the authors indicate that the data continue to support the WHO treatment recommendations for the use of dolutegravir in pregnancy as it has superior virologic efficacy, rapid suppression of viral load after initiation of treatment, and that this it is maintained throughout the lactation period. In the case of efavirenz, despite having evidence of virological suppression, the potential for transmission during breastfeeding stands out.

Source: POZ / Elaboración propia (gTt-VIH)
References: Thokozile R. Malaba et al. DolPHIN2 final results dolutegravir vs efavirenz in late pregnancy to 72w postpartum. Conference on Retroviruses and Opportunistic Infections, Oral Abstract Session, 2021.

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