With the availability of different antiretroviral therapies (ART) to manage HIV—along with new discoveries about the risks and benefits of each drug—comes the opportunity to revise prescribing recommendations. When the World Health Organization (WHO) sought input for an update of its 2019 Antiretroviral Guidelines
, limiting the choices to dolutegravir- or efavirenz-containing regimens for people initiating ART, a team of investigators from across the globe jumped in.
The team, led by Andrew Phillips, PhD, an epidemiologist at the Institute for Global Health, part of University College London, undertook a modeling study that looked at the pros and cons of ART regimens containing either dolutegravir or efavirenz in a population of women taking the drugs around the time of conception. By examining variables such as medication cost, unwanted weight gain, risk of neural-tube defects
, transmission rates from mother to baby, CD4 counts, and viral resistance, the investigators concluded that dolutegravir-containing ART regimens provide the most benefit overall. The findings of their modeling study were published in The Lancet HIV.
Dolutegravir has been shown to be quite potent, with a much lower likelihood of patients experiencing resistance to it than to efavirenz (13 times less likely, according to the authors). It’s also an easier drug to tolerate, meaning people are less likely to stop taking it than they are efavirenz.
“The main side effects of efavirenz are neurologic, such as dizziness,” Phillips told Contagion
®. The investigative team was aware that previous studies had raised questions about dolutegravir’s safety profile, specifically the risk of babies born with neural-tube defects. The drug also was found to cause weight gain
—an average of 6 kilograms over 48 weeks, or more than 13 pounds, in 1 study—which itself can cause pregnancy complications.
After conducting the modeling scenarios, the team concluded that even with dolutegravir’s risks it was an appropriate drug for women taking ART for the first time. “Considering outcomes for babies, the higher number of neural-tube defects and stillbirths and neonatal deaths associated with higher weight in mothers was substantially outweighed by the lower number of children born with HIV with the policy of tenofovir, lamivudine, and dolutegravir [taken together as ART] in women intending pregnancy,” they wrote in their report.
The investigators found that dolutegravir-containing ART regimens are more cost effective than those containing efavirenz in 87% of the situations they forecast, mainly due to less use of second-line drugs and fewer HIV-related complications that would require expensive care.
Use of dolutegravir was more conducive to improved health in 83% of the forecast scenarios, mostly due to the rarity of resistance to dolutegravir. They calculated that the lowering of the death rate of women on regimens containing dolutegravir, reduced to 0.36 per 100 person-years, would equal 1800 fewer deaths annually in women in Zimbabwe alone. The team’s modeling scenarios all were based on countries with a population of about 10 million. Their conclusions and recommendations apply only to women beginning ART, they stressed, not those contemplating a switch from 1 regimen to another.
Although the modeling forecasts took into account a variety of scenarios reflecting life in sub-Saharan Africa, the updated WHO guidelines for ART initiation in pregnant women or those intending to conceive are applicable in more developed nations. “The attributes of the drugs are mainly likely to be similar regardless of context,” Phillips told Contagion
®. “The WHO guidelines are not only intended for low-income settings.”
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