The 2022 International Congress on Drug Therapy in HIV Infection—known as HIV Glasgow 2022—was held October 23–26 in the Scottish capital. Following are reports by aidsmap.com on two of the many notable sessions.
A better second-line of defense
After viral rebound, dolutegravir-based treatment is more likely to suppress HIV
by Keith Alcorn
Dolutegravir-based treatment is significantly more likely to result in re-suppression of HIV after viral rebound than treatment containing efavirenz, a meta-analysis of four large clinical trials has reported.
The findings were presented by Dr. Andrew Hill of Liverpool University.
The capacity of an antiretroviral regimen to re-suppress HIV after viral rebound above the limit of detection is an especially important question for lower- and middle-income settings where a limited number of regimens are available.
If first-line treatment fails, second-line treatment is considerably more expensive, so it is critical to understand the likelihood of viral re-suppression when people continue with their existing regimen and receive enhanced adherence counselling, in line with World Health Organization guidelines for the management of viral rebound.
The question becomes even more critical in second-line treatment, where there are fewer options for replacement treatment.
Dolutegravir-based treatment is recommended as a preferred option for first-line treatment due to its high barrier to resistance. Treatment with dolutegravir is also better tolerated than efavirenz-based treatment.
To evaluate whether dolutegravir-based treatment is more likely to lead to re-suppression of HIV after viral rebound, investigators pooled data from four large studies that compared dolutegravir to efavirenz-based or protease inhibitor-based treatment in sub-Saharan Africa.
Studies included in the analysis were:
ADVANCE, a comparison of dolutegravir or efavirenz, paired with either tenofovir disoproxil/emtricitabine or tenofovir alafenamide/emtricitabine, carried out in previously untreated people in South Africa.
NAMSAL, a comparison of dolutegravir or lower-dose efavirenz, paired with tenofovir disoproxil/lamivudine, carried out in previously untreated people in Cameroon.
DOLPHIN-2, a comparison of dolutegravir and efavirenz, paired with tenofovir disoproxil/lamivudine, carried out in previously untreated pregnant women in Uganda.
VISEND, a comparison of several NRTI combinations when switching to second-line treatment containing dolutegravir or a boosted protease inhibitor.
The analysis looked at viral re-suppression rates in participants in the four studies who had experienced viral failure (a viral load above 1,000 copies after week 24) and did not change treatment. Participants with viral failure could be classified either as re-suppressing HIV, having persistent virus levels above 1,000 copies or lost to follow-up.
In ADVANCE, viral failure rates were similar across the three study arms (8–13%) but re-suppression rates ranged from 23% in the efavirenz study arm to 41% and 59% in the dolutegravir arms. The same pattern was evident in NAMSAL; 15% and 17% experienced viral failure in the two study arms but whereas 60% in the dolutegravir arm re-suppressed viral load, only 27% in the efavirenz arm did so.
In VISEND, people who entered the study with viral load above 1,000 copies/ml were more likely to experience viral failure than those with baseline viral load below 1,000 copies/ml. Viral failure occurred more often in the boosted protease inhibitor study arms (20–27%) than in the dolutegravir arms (12–18%). Re-suppression occurred less often in the boosted protease inhibitor arms (17–19%) than in the dolutegravir arms (34–41%).
In DOLPHIN-2, viral failure and re-suppression did not differ substantially between the dolutegravir and efavirenz arms.
In the meta-analysis, the rate of viral re-suppression was significantly higher for dolutegravir than efavirenz (p=0.04).
In three of the four studies, sustained viraemia above 1,000 copies/ml was more common in those with viral failure who did not receive dolutegravir. For example, in ADVANCE, 52% of those with viral failure in the efavirenz arm had a sustained viral load above 1,000 copies/ml after week 24 of the study, compared with 14% and 27% in the dolutegravir arms. The same pattern was seen in NAMSAL and VISEND, but not in DOLPHIN-2.
Presenting the study findings, Dr. Andrew Hill said that more research was needed to assess how much adherence counseling and sustained viraemia are required before people taking dolutegravir are offered a new regimen. He pointed out that new South African treatment guidelines only recommend a switch from dolutegravir if integrase inhibitor resistance is detected.
Professor Linda-Gail Bekker of the Desmond Tutu HIV Centre at the University of Cape Town said that long-term follow-up of people who re-suppress viral load on dolutegravir is needed. She asked whether people who re-suppress ultimately fail on dolutegravir, as has been previously shown for NNRTI-based treatment.
Untreated heart risk
People with HIV aren’t getting medication to prevent heart disease, despite high risk
by Keith Alcorn
Almost half of a large European cohort of people with HIV were at very high risk of heart attack by 2019, but a substantial proportion were not receiving medication to lower blood pressure or lipid levels, investigators from the RESPOND study reported.
One-third of people eligible for medication to reduce their blood pressure were not receiving it in 2019 and 43% were not receiving medication to reduce lipid levels, the study found. A similar proportion were not receiving medication to control their blood sugar.
European AIDS Clinical Society guidelines recommend that all people with HIV who have a greater than 10% risk of heart attack, stroke or major heart surgery as a result of heart disease in the next ten years should be prescribed lipid-lowering medication, such as a statin. Treatment for raised blood pressure is especially recommended for this group too.
People with HIV have a higher risk of cardiovascular diseases (diseases of the heart and circulation) than others of the same age, partly due to HIV but also because they are more likely to smoke.
Guidelines recommend a variety of measures to reduce the risk of serious cardiovascular disease, but studies have shown that individual measures are unevenly applied. However, as cardiovascular disease is caused by multiple factors, it is important to understand where there are gaps in risk reduction and whether those gaps disproportionately affect specific groups of people.
The RESPOND cohort is a large international cohort collaboration designed to investigate long-term health outcomes in people with HIV taking antiretroviral treatment in Europe and Australia. RESPOND investigators at the University of Copenhagen, Denmark, used the cohort data to look at the use of preventive measures against heart disease in people with HIV.
The study investigators assessed whether any of seven preventive measures had been adopted to reduce cardiovascular risk in people with a very high risk of heart attack or stroke. A very high risk was defined as a 10% or greater risk within ten years of a serious cardiovascular event such as heart attack, stroke or death from a serious cardiovascular event, or surgery for major heart disease caused by hardening of the arteries or blockages due to raised cholesterol.
The preventive measures were:
- Weight loss (>7%) for people with body mass index of 30 or above (clinical obesity)
- Stopping smoking
- Discontinuation of antiretrovirals previously associated with cardiovascular disease (lopinavir/ritonavir, darunavir or abacavir)
- Use of medication to reduce blood pressure in people with high blood pressure
- Use of ACE inhibitors or angiotensin receptor blockers (ARB) in persons with high blood pressure and/or diabetes
- Use of antidiabetic medication in people with diabetes
- Use of medication to lower cholesterol or triglycerides in people with raised lipid levels.
The study looked at the risk of heart disease and the use of preventive measures in 22,050 cohort participants between 2012 and 2019. The absolute number of participants differed year by year as people joined or left cohorts.
Overall, 75% of participants were male, 45% had acquired HIV through sex between men and 14% through injection drug use. Seventy-five percent were white. Forty-four percent were smokers, 42% had elevated lipids, 19% had high blood pressure, 25% were overweight and 8% were clinically obese. Five percent had diabetes. At baseline, 33% had been exposed to abacavir, 26% to lopinavir and 16% to darunavir.
The proportion with very high risk of heart disease rose from 31% in 2012 to 49% in 2019. People with a very high risk of heart disease differed from the overall cohort in several ways. They were more likely to have raised lipid levels (63%), high blood pressure (38%) and diabetes (15%) and were more often smokers (57%) than the cohort as a whole. They were more likely to have been exposed to lopinavir (36%), abacavir (52%) and indinavir (33%) (a marker of living with HIV for longer, as indinavir was largely replaced by other drugs after 2000).
People at very high risk of heart disease were older than the cohort as a whole (a median age of 55 years vs. 45 years).
The use of three measures significantly increased between 2012 and 2019:
- Discontinuation of lopinavir/ritonavir
- Discontinuation of darunavir
- Discontinuation of abacavir after more than six months of treatment with the drug.
But there was no significant change in the proportions who received medication to treat high blood pressure (66%) between 2012 and 2019, nor in the proportion receiving lipid-lowering drugs (57%) or ACE inhibitors or ARBs (42%).
There was no change in the proportion of smokers who stopped smoking between 2012 and 2019 (7%) and the proportion with weight loss actually fell slightly in the same period (from 11.5% to 10.5%), as did the proportion receiving medication to treat diabetes (from 63% to 57%).
Multivariable analysis of preventive measures by sub-group showed that the use of medication was more common in older people, whether comparing over- and under-50s, or over and under-40s. But there was no age-related difference in the use of other preventive measures.
Women were less likely to receive ACE inhibitors or ARBs, but otherwise, there was no gender difference in the use of preventive measures.
Participants with a viral load below 200 copies/mL, and people who acquired HIV through injection drug use, were less likely to use lipid-lowering drugs or to stop smoking.
The study investigators say that their findings highlight the need for increased awareness of guidelines for management of cardiovascular risk factors.
Reprinted with permission from aidsmap.com. More coverage of HIV Glasgow 2022 can be found at aidsmap.com/conferences/hiv-glasgow-2022.