Friday 8 March 2019

Long-acting injectable HIV treatment maintains viral suppression

A combination of two long-acting injectable anti-HIV drugs taken once monthly had a very low rate of treatment failure and a favourable safety profile, according to results from two phase III trials presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2019).

Dual injections of cabotegravir, an experimental integrase inhibitor, and the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine, currently available as a pill (Edurant), maintained viral suppression for people switching from a standard oral regimen (in the ATLAS trial) and for previously untreated people after a short three-drug induction period (in the FLAIR trial).

In both studies, pharmacokinetic data showed that cabotegravir and rilpivirine concentrations in the blood remained above effective thresholds throughout the study and were similar to levels reached with the corresponding oral formulations.

Study participants expressed a high level of satisfaction with monthly injections compared with daily pills, and nearly all said they would prefer to use the injectable method.

Neural tube defects and integrase inhibitors: still waiting for stronger evidence

Researchers are still unable to determine if exposure to integrase inhibitors around conception and in early pregnancy increases the risk of neural tube defects in infants, research presented this week at CROI 2019 shows.

A neural tube defect occurs when the spinal cord, brain, or related structures do not form properly. 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, so it is important to rule out any harmful effects of drugs taken at this time.

In 2018, concerns were raised after a higher rate of neural tube defects was observed in infants exposed to dolutegravir around conception and in the first three months of pregnancy in the Tsepamo study in Botswana. The World Health Organization reacted to the findings by issuing guidance that women who could potentially become pregnant should take effective contraception if they opt to take dolutegravir.

Researchers are now checking whether the safety signal from the Tsepamo study represents an increased risk or whether these cases were a local anomaly or due to chance. Dolutegravir is an integrase inhibitor and studies have also looked at a similar drug, raltegravir.

Some large studies presented at CROI 2019 found no increased risk of neural tube defects. However, researchers also highlighted the limitations of surveillance systems and called for further prospective studies on antiretrovirals. Further data from the Tsepamo study are expected later this year.

‘Molecular scissors’ successfully remove HIV genes from all tissues in infected monkeys

A team of researchers at Temple University in Philadelphia, USA has removed the retroviral genes from the cells of two monkeys infected with SIV, the monkey analogue of HIV. The research, presented at CROI 2019, used a gene-snipping enzyme (CRISPR/Cas9), contained within the shell of a common cold-type virus, to successfully remove the SIV genes from a majority – and possibly all – cells in all the monkeys’ organs where levels were measured.

As the monkeys in this experiment were euthanised after the intervention so all tissues could be biopsied, the experiment cannot be said to amount to an SIV cure. But the comprehensive nature of the results is impressive, and any attempt to culture SIV from the immune cells in the blood of treated monkeys produced no virus. The next step will be to give the same therapy to SIV-positive monkeys on antiretroviral therapy and then interrupt treatment to find out if the SIV reappears.

The length of time people with HIV in the US remain infectious is falling slowly

In 2016, for more than half of people diagnosed with HIV in the United States, it took more than three years to be diagnosed, and more than five months after diagnosis for their viral load to be suppressed. This was the finding of a study by researchers at the Centers for Disease Control and Prevention (CDC), presented at CROI 2019, which used routinely collected data from new HIV diagnoses and CD4 and viral load results.

Early diagnosis and treatment for HIV is important both for the health of the person with HIV and in terms of HIV prevention. People with undiagnosed HIV are more likely to pass HIV on to their partners. Taking effective HIV treatment stops HIV from being passed on during sex.

The study found that the median time from infection to diagnosis reduced from 43 months in people diagnosed in 2012, to 39 months in people diagnosed in 2016, a decrease of 9% over the four-year period.

Much more progress has been made in reducing the median time from diagnosis to viral suppression. Between 2012 and 2016, this fell from eight to five months, a 38% decrease.

COPD increases the risk of heart attack in people with HIV

Chronic obstructive pulmonary disease (COPD) increases the risk of heart attack in people with HIV, US researchers reported at CROI 2019 this week.

COPD refers to chronic lung disease that causes breathing difficulties. COPD is one of the most common chronic diseases in people with HIV. Even after adjusting for smoking, a recent meta-analysis found that people with HIV had a 15% higher risk of suffering from COPD.

Severe COPD is associated with an increased risk of heart attack in the general population. However, previous studies have not shown an increased rate of heart attack in people with HIV.

For this study, researchers investigated whether COPD raised the risk of heart attack by working with eight large HIV clinics in the US, covering 22,596 people with HIV, and looking at the data for people with COPD.

After adjustment for smoking and duration of smoking, people with COPD were twice as likely to suffer a heart attack during the follow-up period (median 3.44 years). More research is needed into the mechanisms leading to a raised risk of heart attack, and into preventative and therapeutic strategies.

How many people who have used PrEP get HIV the same year?

A study from New York City, presented at CROI 2019, aimed to find out: how many people who have used pre-exposure prophylaxis (PrEP) during the previous year are diagnosed with HIV?

PrEP is an effective way of preventing HIV, by means of an HIV-negative person taking antiretroviral drugs to protect themselves from acquiring HIV. However, the same drugs used for PrEP are used in treating HIV and concerns have been raised about the potential for drug resistance to develop if someone with undiagnosed HIV takes PrEP.

A number of randomised controlled trials of PrEP have reported having participants who acquired HIV at the time they started PrEP or just before, and some did acquire drug resistance. But how often this happens in PrEP provision programmes is not known.

The study presented at CROI looked at routinely collected data on 3685 people diagnosed with HIV in the last year and identified only 91 people (2.5%) who had used PrEP in the year before diagnosis. Their average duration of PrEP use had been 106 days, but the average period between starting PrEP and being diagnosed was 250 days, suggesting many had stopped PrEP some time before diagnosis.

There was more drug resistance in former PrEP takers who acquired HIV. However, this was solely resistance to the emtricitabine component of PrEP and there were no instances of the K65R tenofovir resistance mutation in people who had used PrEP.

One-third (33%) of people who had used PrEP were diagnosed with acute, i.e. very recent, HIV infection versus 9% of people who had never used PrEP.

Dr Kavita Misra, presenting, said that although the results were generally reassuring, they underlined that “rigorous HIV screening was critical” before starting people on PrEP.

Integrase inhibitor treatment leads to greater weight gain

More evidence that HIV integrase inhibitor treatment is associated with weight gain, and that people gain more weight after beginning treatment with an integrase inhibitor than people taking other drug classes, was presented this week at CROI 2019.

Weight gain on integrase inhibitor treatment was first flagged up in late 2018 and since then, other research groups have been looking at weight gain in a wider range of patient groups.

The North American AIDS Cohort Collaboration found that among people starting treatment for the first time, treatment with an integrase inhibitor was associated with greater weight gain than treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI). The analysis looked at 24,001 people who started treatment between 2007 and 2015. After five years on treatment, people taking an integrase inhibitor had gained a median of 6kg, compared to 4.3kg for people who started an NNRTI.

Two smaller studies also found an association between integrase inhibitor treatment and weight gain and one other study found no association.

Is this weight gain caused by antiretroviral drugs or is it a product of environments that encourage people to eat unhealthily and be physically inactive? Moderating a discussion on weight gain after starting treatment, Jane O’Halloran of Washington University, St Louis, pointed out that up to half of adults starting antiretroviral therapy in the United States may already be obese. Weight gain after starting treatment may be occurring in adults who already have diets and lifestyles that predispose them to further weight gain.

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