Dramatic decline in proportion of people with extensive resistance to anti-HIV medications

The proportion of people in the United States with extensive resistance to antiretroviral therapy (ART) and limited treatment options declined markedly after 2012, in large part thanks to the availability of potent new drugs, according to research presented to the 10th International AIDS Society Conference on HIV Science (IAS 2019) in Mexico City. Since 2012, only 1% of people who have taken ART have had extensive resistance.

Combination ART regimens first became available in 1996, transforming the prognosis for many people with HIV. However, many of the early drugs lacked potency. This meant that resistance could easily develop, especially if adherence to their often-complicated dosing regimens was less than perfect.

Since then, more powerful drugs less vulnerable to resistance, and with easy adherence schedules, have been developed, including boosted protease inhibitors such as darunavir and the integrase inhibitor class of anti-HIV drugs. New drugs for people with extensive resistance, such as ibalizumab, fostemsavir and leronlimab (PRO 140), have recently become available or are being studied.

Glossary

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

nadir

Lowest of a series of measurements. For example, an individual’s CD4 nadir is their lowest ever measured CD4 count.

treatment-experienced

A person who has previously taken treatment for a condition. Treatment-experienced people may have taken several different regimens before and may have a strain of HIV that is resistant to multiple drug classes.

integrase inhibitors (INI, INSTI)

A class of antiretroviral drugs. Integrase strand transfer inhibitors (INSTIs) block integrase (see ‘integrase’). Blocking integrase prevents HIV from replicating.

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

A team of US investigators wanted to track changes in the proportion of ART-experienced people with antiretroviral resistance and limited treatment options ('heavily treatment experienced'). They examined data from between 2000 to 2017 for seven sites across the US enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems.

'Heavily treatment experienced' people were defined as people who had taken ART and who, due to drug resistance, now had only two antiretroviral classes available to them, with no more than two viable drugs in each class.

The study population consisted of approximately 27,000 ART-experienced people. Most were male (81%); 43% were white and 41% black; and 53% were in the men who have sex with men HIV risk category. The median age was 46 years.

Prevalence of multidrug-resistance was a little over 5% at the start of the study, peaking at 7.5% in 2004. It then fell dramatically to just under 2% in 2007, before declining further, and between 2012 and 2017 was stable at approximately 1%.

People entering care in 2009-11 had an 80% lower risk of requiring multiple regimens and developing extensive drug resistance compared to those entering care in 2006-08 (aHR = 0.20; 95% CI, 0.09-0.42). Similarly, those entering care in 2012-2014 had a 76% lower risk than those entering care in 2006-08 (aHR = 0.76; 95% CI, 0.13-0.51).

The median nadir (lowest ever) CD4 cell count was just 71 cells/mm3 in those with extensive resistance, compared to 240 cells/mm3 in those without. People with extensive resistance had a median baseline viral load of just under 200,000 copies/ml, compared to just over 50,000 copies/ml in those without extensive resistance. Nadir CD4 and baseline viral load were significantly associated with a greater risk of developing extensive drug resistance, whereas neither changing treatment because of treatment failure nor the number of drugs ever taken were.

The investigators conclude that the prevalence of extensive drug resistance among ART-experienced patients was stable in the early ART era, declining after 2006-08 and falling to 1% in the contemporary treatment era. This pattern suggests that the decreases are indeed due to the introduction of new drugs with a higher barrier to resistance, leading to improvements in treatment and care.

References

Bajema K et al. Prevalence of heavily treatment-experienced persons with HIV in the United States, 2000-2017. Tenth International AIDS Society Conference on HIV Science (IAS 2019), abstract MOPEB246, 2019.

View this abstract on the conference website.