Whether 15 million on antiretroviral therapy (ART) by 2015 is a realistic target or just a dream is posing the question in the wrong way. The real question is: how can we turn our dream of having 15 million HIV-infected people receiving adequate antiretroviral therapy in 2015 into reality?
This issue of Current Opinion in HIV and AIDS, although far from comprehensive, provides building blocks to attain that goal, points out particular opportunities, but also identifies some of the obstacles that need to be overcome.
The first article by Duncombe et al. (pp. 4–11) sets the stage by summarizing the WHO/UNAIDS Treatment 2.0 strategy. No need to duplicate or add to that here, because the article provides a thorough update on where we stand. One element needs to be highlighted, however: contributions of international donors have been stagnating over the past years, and although there is a continued increase in domestic funding, most African countries are far from reaching the Abuja Declaration targets for spending on healthcare. Sure, efficiencies in healthcare delivery can be improved , and the striking levels of fungibility or crowding out  may be tackled by innovative ways of donor financing . But if there is too little money overall to provide decent healthcare, targets cannot be met.
The second article by Vittoria and Vella (pp. 12–18) provides a very nice overview of the evolution of WHO HIV treatment guidelines, adapting to changing insights and possibilities throughout the years in an ever more timely manner. It also points at future trends, which take into account the beneficial effects early treatment can have on the health of individuals, HIV transmission, the incidence of tuberculosis and models of care delivery. If we do not succeed in simplifying models of care delivery, by decentralization and task-shifting a.o., we will be unable to reach the 15 million by 2015 target.
The third article, by Hamers et al. (pp. 19–26) and the fourth article, by Sohn et al. (pp. 27–33) focus on transmitted HIV drug resistance in Africa and Asia, respectively, and point to an emerging and in some countries, like Uganda, already sizable problem. The Hamers article also presents data on the high rate of drug resistance mutations in those failing first-line therapy. It is clear that surveillance of both transmitted and secondary HIV drug resistance and measures to minimize the risk of their emergence (such as preventing drug stock-outs and increasing adherence) should be an integral component of the continuing ART scale-up. The 15 million target stands for 15 million people on effective, not failing, highly active antiretroviral therapy.
Hill (pp. 34–40), in the fifth article, identifies three main problems with the current ART standard of care for many people in resource-poor settings: a large proportion of those on treatment are still taking stavudine-containing ART; there is limited diagnostic support – access to plasma viral load and drug resistance testing is still rare, which leads to late diagnosis of therapy failure and accumulation of drug resistance mutations; access to second-line treatment is limited. Thus, current practice often does not meet the standards deemed necessary by Hill to achieve ‘Universal Access’: a simple system of treatment, using a sequence of low-cost, coformulated antiretrovirals with strong efficacy profiles, nonoverlapping resistance profiles, and safety issues which are manageable with minimal medical expertise. He argues that only a relatively small subset of antiretrovirals may be needed for first-line, second-line and potentially third-line treatment in large-scale treatment access programs, and has several creative ideas about how this could be achieved in the most cost-effective manner, with a focus on ongoing research to use lower dosages of drugs (’dose-optimization’) which are cheap to manufacture. One can argue whether stavudine should have been included in this list, but, overall, simplifying therapeutic algorithms and lowering the dose and thus the cost of individual drugs are essential ingredients of a more effective scale-up.
The sixth article (pp. 41–49), by the ‘fathers’ of Treatment as Prevention (TasP), advocates passionately for expansion of combination HIV prevention with an emphasis on the merits of expanding treatment: there is increasing evidence of health benefits of earlier treatment, a sharp reduction in incidence of tuberculosis in HIV-infected individuals, and with viral suppression through effective ART the risk of passing on the virus from a person living with HIV to a negative partners is close to zero. The authors remind us about the early skepticism regarding the feasibility and advisability of delivering ART in resource-poor settings, and how these skeptics have been proven wrong. Yes, we should never ever be discouraged by ‘the nattering nabobs of negativism’ (to use a phrase from the recently deceased William Safire). But we can also not be naïve and ignore the potential risks. The path to ‘Test and Treat’ will be paved by identifying – and managing – the potential risks; long-term side effects, and development of significant drug resistance, for example, because of breeches in adherence in particular of people living with HIV who have never been sick and as such have not felt themselves the dramatic benefits of treatment and full reconstitution of ill-health. The question should be less whether or not to treat earlier. But much rather about the ‘how’ and what needs to be in place to minimize, track and manage the potential risks. Let us move intelligently, and while proceeding, watch carefully for possible negative effects to take corrective action, and take the emerging results and lessons of ongoing TasP demonstration projects into account.
The seventh article, by Hankins and Dybul (pp. 50–58), is a thorough review of the evidence for pre-exposure prophylaxis (PrEP), with either local (e.g. vaginal microbicides) or systemic (e.g. oral) use of antiretrovirals. Based on the positive results of several clinical trials, oral PrEP with Truvada [tenofovir disoproxil fumarate/emtricitabine (TTDF/FTC)] has now been approved by the United States Food and Drug Administration (FDA) to reduce risk of sexually acquired HIV infection in high-risk adults. Public health experts are struggling with how to translate scientific findings from PrEP effectiveness trials into real-world implementation. For several reasons PrEP cannot be seen in isolation from treatment, and thus deserves a place in this issue of Current Opinion in HIV and AIDS. First: the same drugs (TDF and FTC) that are used for PrEP are a mainstay of ART regimens (for this purpose lamivudine is considered similar to FTC), which is not an ideal situation considering the risk of HIV drug-resistance development. Second, both human and financial resources for the treatment scale-up are already limited; are we now going to spend resources on these relatively expensive drugs for prevention, while, in addition to the effect of HIV treatment on HIV transmission, other HIV prevention modalities are available (male and female condoms, male circumcision)? Hankins and Dybul carefully review the prerequisites for, challenges to and dilemma's of a PrEP rollout. They also briefly review exciting products in the pipeline, including long-acting agents.
The cascade of HIV care, which has the ultimate aim to achieve and undetectable plasma viral load – for the benefit of the individual and to prevent onward transmission – goes way beyond ‘Test and Treat’. It also involves linking people to care after a positive HIV test, retaining them in care, getting them to initiate ART (if they want so), and getting them to adhere to the treatment regimen. All assuming that the care given is adequate, and that the antiretrovirals are present every time and of good quality. In the eighth article of this issue, with the catchy title ‘Patching a Leaky Pipe’, Kilmarx and Mutasa-Apollo (pp. 59–64) review the recent literature on these multiple Achilles’ heels of the treatment scale-up. Fixing just one or two is not enough: they can all work as ‘chain terminators’. Carefully examining the gaps at each step of the cascade, country by country and community by community, will be among the most useful approaches for planers and decision makers to improve scale-up and quality of care – essential elements to reaching and keeping the 15 million on ART.
Article number nine, by Samuel Oti (pp. 65–69), who has the privilege to work at the unique African Population and Health Research Centre in Nairobi, is a compassionate and well reasoned plea for a coordinated response to HIV and noncommunicable diseases (NCDs). It is amazing that the advantages of this are not yet evident to everyone. How can we defend testing every adult for HIV and not take a blood pressure measurement at the same time. Hypertension is the biggest risk factor for premature death in the world  and its treatment is relatively straightforward and affordable. To secure continued funding for HIV it is essential to show that this money adds value beyond HIV and helps to build viable and sustainable health systems.
Last but not least, article number 10 in this issue, by ‘t Hoen and Passarelli (pp. 70–74), looks at the role of intellectual property rights in HIV treatment access. It is hard to understand for us, why thus far only one research-based pharmaceutical company (Gilead) has had the courage and common sense to contribute to the Medicines Patent Pool. What are the others afraid of and what do they want to accomplish? However, we are living in a rapidly changing world and access to medicines is a complex issue beyond licensing agreements. With significant economic growth in the developing world the old concepts of rich and poor countries are increasingly invalid. Already today, the significant majority of all people living with HIV is living in middle and high-income countries, up from less than one-third, 10 years ago. And this trend is to continue. We need new approaches to access and equity, differential pricing approaches that address poverty within a given country, more systematic approaches to price negotiations that protect the smaller and less powerful states in their attempts to negotiate access to life-saving medicines, and the full use of TRIPS flexibilities including compulsory licensing if we are to reach the 15 million, and beyond.
All in all, although some pieces, like healthcare financing, are missing, this issue of Current Opinion in HIV and AIDS presents a relevant mix of articles about opportunities of and challenges to a continued antiretroviral therapy scale-up.
It has been a privilege to have served as its editors.
J.M.A.L. and B.S.
Conflicts of interest
J.M.A.L. institution has been receiving educational grants from the following pharmaceutical companies: Abbott, Boehringer Ingelheim, Bristol Meyers Squibb (BMS), Crucell, Gilead, ViiV, Johnson and Johnson, Merck, Mylan, and Roche. I have received honoraria for speaking engagements or consulting from Bristol Meyers Squibb, Gilead, Roche and Tibotec (Johnson and Johnson).
B.S. has no conflicts of interest.