The Antiretroviral Pipeline
The Antiretroviral Pipeline By Simon Collins
Introduction Current HIV drugs are sufficiently safe, potent, and effective for recent modeling studies to suggest that, for someone newly infected with HIV, life expectancy should be approaching that of an HIV-negative person.1,2 This is dependent on access to care and treatment, and such models usually exclude complications such as hepatitis C or tuberculosis coinfection or ongoing drug use. Therefore, any review of pipeline drugs must acknowledge that these assumptions for normalizing life expectancy currently apply to a minority of patients globally unless universal access and uptake can be achieved. At levels of viral suppression to <50 copies/ml, HIV evolution is not slowed, but stopped,3 with the evidence suggesting that residual virus is more likely to originate from latently infected resting cells than from ongoing replication in a part of the body not reached by treatment.4 Treatment is more effective than people realize. Recent studies using more sensitive viral load tests suggest that perhaps more than 50% of people suppressed to <50 copies/ml generally have HIV RNA <5 copies/ml.5,6 At these low levels, further intensification has no additional impact on viral load in plasma or in sanctuary sites such as the central nervous system.7,8 New drugs and classes need to be designed to increase flexibility to adherence with the potential for new delivery methods and smaller molecular weight formulations to reduce costs. So the bar for new drugs is set higher, but this, by definition, has always been the case. Virological failure rates are low. In some settings, rates of viral failure in people on stable suppression therapy are less than 5% annually,9 supported by pharmacokinetic profiles that allow the maintenance of therapeutic levels of some drugs after the strict dosing time.10 However, rates for switching HIV treatment due to toxicity or tolerability are significantly higher, showing that tolerability is still clinically significant. Other examples of unmet antiretroviral (ARV) need include combinations that: â&#x20AC;˘ treat people with multidrug resistance â&#x20AC;˘ protect against or reverse central fat accumulation
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