News from IAS 2019

The Tenth International AIDS Society Conference on HIV Science (IAS 2019) was held in Mexico City last month. This edition of HIV update focuses on the top news from IAS 2019 for people living with HIV in the UK. Visit our IAS 2019 webpages for all our news reporting from the conference.

Dolutegravir safety in pregnancy

Dolutegravir is a widely used anti-HIV drug in the integrase inhibitor class. It is marketed as Tivicay and is a component in the combination pills Triumeq, Juluca and Dovato.

In 2018, regulatory agencies warned that women with HIV who could become pregnant should not use dolutegravir without effective contraception. These warnings followed a report from Botswana of a higher frequency of birth defects in babies born to mothers who became pregnant while taking dolutegravir.

The study in Botswana started in 2014. It expanded in 2018 from 8 hospitals to 18 and has now recorded information on 119,477 deliveries up to March 2019.

An update from the study was presented to the IAS 2019 conference. The researchers have found that although there is still a small increased risk of neural tube defects in babies born to mothers who were taking dolutegravir early in pregnancy, the risk is lower than the initial results had suggested.

A neural tube defect occurs when the spinal cord, brain, and related structures do not form properly. Spina bifida – a malformed spinal cord – is the most common neural tube defect. The most common cause of neural tube defects is a lack of folic acid during pregnancy, but defects can also be caused by some medications. The risk of neural tube defects is highest at the time of conception and in the first trimester of pregnancy.

The results presented at IAS 2019 show that the difference in risk between dolutegravir and other antiretrovirals is the equivalent of two extra cases of neural tube defects for every 1000 women exposed to the medication.

A smaller study in Brazil, also presented at the conference, included 1468 women who had taken dolutegravir, raltegravir or efavirenz during pregnancy, and found no neural tube defects.

Given that lack of folic acid is an important cause of neural tube defects, several speakers at the conference drew attention to the lack of folate supplementation for pregnant women in Botswana and other countries.

In the UK, folic acid supplements are recommended for women who are trying to get pregnant and for the first 12 weeks of pregnancy.

Dolutegravir and weight gain

Putting on a little weight after starting HIV treatment is a common event, especially if you were unwell beforehand. It’s often called a 'return to health' weight gain.

However, there is evidence that some anti-HIV medications may cause additional weight gain, particularly those from the integrase inhibitor class. This class of medications is extremely effective in treating HIV and is recommended as a preferred option in many countries.

The results of two large clinical trials in sub-Saharan Africa were reported to the IAS 2019 conference. They found that people taking HIV treatment which included the integrase inhibitor dolutegravir gained weight, and this was particularly true of people taking dolutegravir with the newer formulation of tenofovir.

One of the studies was carried out in Cameroon and it involved 613 people, who took either:

• dolutegravir, lamivudine and TDF (the older formulation of tenofovir, tenofovir disoproxil fumarate); or
• efavirenz, lamivudine and TDF.

After 48 weeks, people in the first group had gained a median of 5kg, compared with a 3kg gain in the second group.

The second study, in South Africa, involved 1053 adults and adolescents, who took either:

• dolutegravir, emtricitabine and TAF (the newer formulation of tenofovir, tenofovir alafenamide fumarate); or
• dolutegravir, emtricitabine and TDF; or
• efavirenz, emtricitabine and TDF.

At both 48 and 96 weeks, the first group had gained the most weight. Weight gain was lower in second group and lowest in the third.

In the South African study, there was also a significant difference in weight gain by gender. Men and women taking dolutegravir gained weight to a similar extent up to week 48, but whereas for men weight stabilised after week 48, women continued to gain weight.

Maintaining a healthy weight is important to general health. Substantial weight gain may increase the risk of health conditions such as diabetes, heart disease and some cancers. Longer-term follow-up of the people involved in these studies is needed to evaluate the consequences of weight gain in these groups.

Two-drug HIV treatment

One area of HIV treatment research looks at HIV treatment regimens that involve fewer drugs. Reducing the number of medications people have to take could potentially reduce side-effects and cost. But HIV treatment using just two medications (also called ‘dual therapy’) requires medications that are strong enough to keep viral load fully suppressed and prevent the development of drug resistance.

Research presented to the IAS 2019 conference found that people starting HIV treatment for the first time with a two-drug combination of dolutegravir and lamivudine were just as likely to have an undetectable viral load after 96 weeks as people taking a standard three-drug combination.

The results came from clinical trials that enrolled 1433 people starting HIV treatment and randomly assigned them to take either dolutegravir plus lamivudine – the antiretrovirals in the Dovato pill – or dolutegravir plus TDF and emtricitabine.

After 96 weeks, 86.0% of people in the dolutegravir/lamivudine group and 89.5% of people in the dolutegravir/TDF/emtricitabine group had an undetectable viral load.

The conference also heard that the same two-drug combination maintained viral suppression in people who switched from a standard regimen. An ongoing trial is comparing the safety and efficacy of switching to dolutegravir/lamivudine versus staying on a three- or four-drug regimen containing TAF. This trial involves 741 people and, at 48 weeks, 93.2% of people who switched to dolutegravir/lamivudine and 93.0% of those who stayed on a TAF regimen had an undetectable viral load.

A further study presented to the conference examined a new anti-HIV medication, islatravir, and its potential to be used in a two-drug regimen with doravirine.

Islatravir is the first nucleoside reverse transcriptase translocation inhibitor (NRTTI). The study found that the combination of islatravir and doravirine (Pifeltro), the recently approved non-nucleoside reverse transcriptase inhibitor (NNRTI) could be effective and well-tolerated as a two-drug regimen.

HIV treatment for people with a lot of drug resistance

The conference heard about a treatment option for people whose HIV has resistance to most other anti-HIV drugs. Fostemsavir is an HIV attachment inhibitor, which prevents HIV from attaching to CD4 cells by sticking to the virus, not the cell.

An ongoing study, presented to IAS 2019, is working with people who have multidrug-resistant HIV and who are not able to control HIV using existing HIV medications. They are taking fostemsavir alongside other HIV medications. After 96 weeks, more than half of the study participants continue to have an undetectable viral load.

Study participants, many of whom had advanced immune suppression, also experienced substantial gains in CD4 cells. Treatment continued to be safe and well-tolerated.