Finally drug giants are collaborating to produce simpler HIV regimens. Anna Poppa looks at why
Efforts to improve global access to HIV treatments got a significant boost in May when the US Food and Drug Administration (FDA), responsible for drug licensing, announced plans to fast-track applications for approval of fixed dose combinations of HIV treatments.
Part of the president’s Emergency Plan for AIDS Relief, this is the first time manufacturers of generic copies of branded HIV drugs have been allowed to seek a US license to sell their products in Africa and developing countries.
The administration’s invitation was not limited to generic drug producers. We’ve since heard of plans by several major manufacturers of patented anti-retrovirals to join forces to develop new, fixed dose combinations. While GlaxoSmithKline and Boehringer Ingelheim intend to work together on co-packaging AZT, 3TC and nevirapine, Gilead, Bristol-Myers Squibb and Merck have reported they’re co-developing a tablet containing three of their drugs; tenofovir, FTC and efavirenz.
So what’s behind this outbreak in big pharma bonhomie? We know the cost of medicines has been an important reason why drugs remain out of reach for the majority of people with HIV worldwide. But fixed dose combinations, where one or more medicines are co-formulated into a single pill, are being favoured for their ability to address some other challenges. Firstly, mobilising a supply of co-formulated, or co-packaged, drugs is simpler than ensuring a steady supply of a larger number of products. But secondly, and importantly, fixed dose combinations are seen as a means of simplifying treatment, so missed doses are reduced and prescription instructions are more straightforward.
Of course it’s not just people with HIV in African countries who might benefit from simplified HIV treatment combinations. In fact, HIV medicine has been moving in this direction for some time. GlaxoSmithKline have developed two fixed dose combinations of their three anti-retrovirals, Combivir and Trizivir. Another is on the way towards final approval right now, this time a once daily combination of abacavir and 3TC. Soon after, these are likely to be joined by a Gilead product containing tenofovir and FTC. All this is in addition to most companies’ continuing efforts to reduce the number of daily doses their products require, and the number of pills per dose.
Regardless of which medicine you take, you only get the full benefits if you take it ‘as prescribed’, which means taking all the doses when they ought to be taken and following any other rules about diet and other medicines. Healthcare workers call this ‘adherence’ or ‘compliance’, and it’s not as easy as it sounds.
If you miss doses of your HIV treatment, the penalties can be harsh. HIV is always looking for a way to develop resistance to medicines designed to control it, and the uneven drug levels you end up with by missing doses are exactly the environment HIV needs for this to happen. Medical research is crystal clear on this, compared to people who take HIV treatments exactly as prescribed, people who miss doses:
Fortunately there’s lots of help available to people taking HIV treatment, and plenty you can do yourself. This could involve anything from setting an alarm to remind you when a dose is due, to regular pep-talks from your healthcare team to keep you motivated. But characteristics of the medicines you take will also be crucial. If you have a choice, then choose treatments easiest for you to manage, remembering you’ll be taking them long-term.
The first anti-viral drug licensed to treat people with HIV/AIDS was AZT (zidovudine). Though now approved for twice daily dosing, when AZT was first used back in the 1980s it had to be taken every four hours, causing continuous disruption to sleep and daily life.
In contrast, treatments taken just once or twice a day can fit into most people’s daily routine fairly easily. The number of pills in your combination is also likely to be important. Research shows adherence to HIV treatments is better, the fewer pills there are to be taken each day.
Food and fluid requirements can complicate pill-taking. Some must be taken on an empty stomach, which usually means no food for two hours before a dose, and for an hour or two after. Others should be taken with a meal or snack. Depending on your eating patterns and preferences, these kind of rules may be intrusive. So medicines which can be taken regardless of what you’ve eaten are often easier to stick with.
When it comes to choosing an HIV treatment combination, the evidence suggests you’ll be less likely to miss doses if you can opt for drugs with:
When HIV treatments are first taken, side-effects such as headaches, nausea, diarrhoea, rashes or a feeling of being ‘high’ or out of sorts can be a problem. These should pass after the first few weeks or months, but if they don’t or your doctor may suggest switching one or other of the drugs for something you may get along with more easily.
Many initial side-effects are not in themselves a significant threat to your physical health, but they should be taken seriously by you and your doctor, if they occur. Side-effects are an important reason why people miss doses of their HIV treatment. A Canadian study found HIV-positive people who had at least one severe treatment side-effect were over twice as likely to report having intentionally missed a dose of HIV treatment than those without.
Some of the more worrisome side-effects of HIV drugs are associated more with longer-term use of treatments. Raised levels of fats such as cholesterol and triglycerides in the blood is a side-effect of most drugs in the protease inhibitor class. In the general population, high blood fats are a risk factor for heart disease, and in extreme cases they may cause pancreatitis, a life-threatening inflammation of an organ involved in digesting food.
So far, our worst fears about an epidemic of heart attacks amongst people taking HIV treatments have not materialised, and overall the benefits outweigh risks over the short-term. Nevertheless, these risks still need to be thought through on an individual level. Before starting treatment combination and at regular intervals while treatment is taken, it’s now recommended, doctors measure your blood fats. If these are high, then HIV treatments which do not cause blood fats to rise may be a better option, assuming viable alternatives are available.
Becoming a medical expert isn’t necessary to live well with HIV, but having some involvement in selecting which drugs you take is important. The Wheel is an easy-to-use computer programme available online at aidsmap.com which can help you to work out how well an HIV treatment combination will fit with your daily routine.
Once you start a new combination, your doctor and healthcare team remain available to help with any problems. If you are having trouble with side-effects or remembering to take your pills, then don’t delay in telling your doctor or a nurse. These are common problems so there is no need to be embarrassed. Stopping medicines or reducing the dose without your doctor’s knowledge is never a good idea, but it’s particularly hazardous with HIV treatment because you run the risk of developing drug resistance, which will mean you have fewer viable treatments to choose from in future.
Finally, whilst it is in your interest to stay informed about HIV treatment tolerability, do not lose sight of the bigger picture. A recent study from the US found rates of response to initial HIV treatment had continuously improved since three-drug combinations were introduced in 1996, in line with increasing use of simpler drug regimens.
