Expert reviews: who are they for?

Who are expert reviews for? This may seem like an obvious question: the aims and scope of EOP state that their audience includes those involved in research and development, regulatory and marketing decision makers in the pharmaceutical industry and decision makers in healthcare provision. However, the expert review of the antiretroviral drug rilpivirine published in the current issue [1] raises the broader question of whose needs are being considered when drug characteristics are being assessed.

HIV/AIDS is overwhelmingly a disease of low- and middle-income countries. Two-thirds of the 34 million people living with HIV/AIDS in the world today live in Africa, and over three-quarters of people currently on antiretroviral therapy live in Africa (5.1 million out of a total of 6.7 million on treatment) [2].

Determining to what extent a particular antiretroviral drug will benefit people living in resource-limited settings requires taking into account the particular clinical, public health and epidemiological specificities of those countries. Expert drug reviews generally summarize data on drug efficacy and safety. In addition to these standard criteria, there are at least five important considerations for patients and providers in resource-limited settings: i) Is the drug safe in pregnancy? ii) Can it be coadministered with antituberculosis (TB) drugs? iii) Are pediatric formulations being developed? iv) Can it be monitored with minimal or no laboratory monitoring? v) Can it be manufactured as a fixed-dose combination?

Safety in pregnancy is important for a number of reasons. HIV diagnoses are often made among women who present at health services because they are pregnant and, as a consequence, a substantial number of patients – up to 1 in 4 in some settings – are first diagnosed to be HIV positive at antenatal care [3]. The majority of people on antiretroviral therapy in Africa are women [4] and up to half of women on antiretroviral therapy intend to have children [5].

TB is a major coinfection of HIV, with more than one in four deaths among people with HIV/AIDS being due to TB [6]. Around one-third of patients initiating antiretroviral therapy in some settings have active TB [7]. The interaction between commonly used antiretroviral drugs (such as nevirapine) and commonly used TB drugs (notably rifampicin) is an important consideration that can complicate efforts to simplify the delivery of care.

Pediatric HIV is even more clearly a disease of the developing world, with nine in ten children living with HIV/AIDS living in Africa (3.1 million out of a global total of 3.4 million). Too few pediatric formulations are currently available [8]. The alignment of treatment recommendations between adults and children has recently been stated as a policy priority of the World Health Organization (WHO), and this will make the need for pediatric data for new antiretroviral drugs all the more important [6].

Laboratory monitoring capacity is very limited in countries with a high HIV burden. Recognizing this, current WHO treatment guidelines for resource-limited settings stress that lack of laboratory monitoring should not be a barrier to starting antiretroviral therapy [9]. Drugs that require specific monitoring (such as tropism determination for maraviroc [10]) are likely to be of limited application in sub-Saharan Africa and, consequently, of little benefit for the majority of people living with HIV/AIDS today. The potential lower efficacy of rilpivirine at higher viral loads, and the low barrier to resistance, are issues that may be manageable in Western settings where access to viral load and genotyping are routine. However, these monitoring tools are rarely available in Africa.

Finally, the development of fixed-dose combinations of antiretroviral medicines has simplified drug supply and storage and has also resulted in medications that are easier to take. Both fixed-dose combinations [11] and once-daily regimens [12] have been found to offer significant advantages in terms of patient adherence – and the possibility of administering rilpivirine as a once-daily, one fixed-dose combination pill is certainly a major strength of this new compound.

These key considerations for resource-limited settings are often overlooked in expert reviews of antiretroviral drugs. Nine expert reviews published in the last 4 years (excluding one written by us [13]) have focused on or included rilpivirine [14-22]. Of these, one addressed safety in pregnancy [15], three highlighted interactions interactions with TB drugs [14,16,17] and two discussed potential formulation as fixed-dose combination [14,17]. None of these reviews mentioned data for safety/efficacy in children and none discussed the consequences of resistance development for resource-limited settings.

The example given by rilpivirine is by no means unique. In reality, most expert reviews of antiretroviral drugs do not place an explicit focus on the patient and program characteristics of resource-limited settings, where the vast majority of people live. Given that more people on antiretroviral therapy live in Zambia than in the whole of the United States (283,863 vs. 268,000), it is crucial that this focus changes [6].

Declaration of interest

The authors state no conflict of interest and have received no payment in preparation of this manuscript.