Robert Steinbrook, MD
Overshadowed by the Zika epidemic, concerns about terrorism and security, and the US presidential election, the global HIV/AIDS pandemic persists, with 2.1 million new HIV infections and 1.1 million deaths worldwide in 2015 (http://bit.ly/2ambo2P). The 21st International AIDS Conference in Durban, South Africa, in July highlighted the remarkable progress since 2000, when the conference was last held in Durban and very few people in Africa received antiretroviral therapy.
At present, 3.4 million people in South Africa are being treated for HIV infection, more than in any other country in the world; between 2005 and 2015 overall life expectancy at birth in South Africa increased from 53.5 years to 62.5 years (http://bit.ly/1swJbPo). In 2000, 490 000 new HIV infections occurred among children throughout the world; in 2010 the figure decreased to 290 000 and in 2015 to 150 000 (http://bit.ly/2ambo2P). Unlike the $10 000 annual cost of HIV treatment in 2000, the price tag for some first-line antiretroviral regimens now is only $100 per year.
The recent conference aimed to catalyze the work that remains—further scientific advances, addressing stigma, discrimination and other structural barriers within society, and securing the political commitment, including financial resources for prevention, diagnosis and treatment (http://bit.ly/2960ttk). However, fewer people may have been listening than in the past. Among the more than 15 000 participants from 153 countries, including 800 media delegates, few journalists from a US newspaper or television network were on-site in Durban. Although the conference was covered from afar, it was relatively underreported in the United States.
THE GOOD AND THE BAD
Progress against HIV/AIDS is invariably a story of both good and bad news, and the conference reports were no exception. The good news was predominantly about preexposure prophylaxis (PrEP) and progress toward an AIDS vaccine. The concerning news was primarily about the epidemic’s stubbornness. Unlike the situation with children, the annual number of new HIV infections among adults has leveled off. After declining from 2.7 million in 2000 to 1.9 million in 2010, new infections plateaued at an estimated 1.9 million annually through 2015. Two-thirds of new HIV infections are in sub-Saharan Africa (http://bit.ly/2ambo2P). No AIDS vaccine exists and until the number of new HIV infections among adults again starts to decrease, ending the pandemic is wishful thinking.
Recently updated World Health Organization guidelines recommend the provision of “lifelong [antiretroviral therapy] to all children, adolescents and adults, including all pregnant and breastfeeding women living with HIV, regardless of CD4 cell count” (http://bit.ly/2aDmypB). Many nations, however, have yet to adopt these guidelines or fully implement them. In 2015, an estimated 17 million people living with HIV were receiving antiretroviral therapy (http://bit.ly/2ambo2P), yet only an estimated 60% of all persons infected with HIV knew their HIV status, 46% of people living with HIV were receiving antiretroviral treatment, and 38% of people with HIV were virally suppressed, and thus less infectious to others (http://bit.ly/29Bjgji). These percentages lag far behind the Joint United National Programme on HIV/AIDS (UNAIDS) 90-90-90 targets to be reached by 2020: that 90% of all people living with HIV know their HIV status, 90% of those who know their status receive sustained antiretroviral therapy, and 90% of those receiving treatment be virally suppressed. The recommended initial regimens in the United States and other Western nations remain expensive and are not the regimens that many people in low- and middle-income nations typically receive.
In 2015, sex workers, people who inject drugs, gay men and other men who have sex with men, as well as clients of sex workers and other sexual partners of people in these groups accounted for an estimated 36% of all new HIV infections in 2015 (http://bit.ly/29Bjgji). New infections in these so-called “key populations,” as well as in adolescent girls and young women in eastern and southern Africa, are the challenge of prevention efforts. HIV-related stigma and discrimination are still widespread; 74 countries criminalize same-sex sexual relationships, and 35 impose HIV-related travel restrictions (http://bit.ly/2ambo2P).
Against this backdrop, donor government funding to support HIV programs in low- and middle-income nations has decreased for the first time in 5 years, from $8.6 billion in 2014 to $7.5 billion to 2015, according to a report released at the conference. The lion’s share came from 2 countries—the United States provided two-thirds and the United Kingdom supplied 13% (http://kaiserf.am/2aN3Hru). Although many at the conference called for billions of additional dollars for HIV/AIDS, prospects for increased or even stable donor funding seem uncertain at best. Among the reasons are competing health and other priorities, the United Kingdom’s withdrawal from the European Union, and political changes in the United States, the United Kingdom, and elsewhere. Treatment and prevention programs that rely on donor funding may have to do more with less, reaching more patients and demonstrating greater efficiency and accountability. Further reductions in the cost of antiretroviral therapy would help, but some countries may have to finance more of their own responses.
SILVER LINING
Some of the most encouraging news from the conference was about PrEP. Multiple reports showed that PrEP with daily tenofovir disoproxil fumarate (TDF)/emtricitabine (available in the United States since 2012 and marketed by Giliead as Truvada) is effective in preventing infections in HIV-seronegative persons at risk, as long as adherence is high. Documented infections were usually associated with lack of adherence. The efficacy of so-called “on demand PrEP,” in which TDF/emtricitabine is used before and after sexual activity, was reported to be high in men who have sex with men according to findings from an open label extension of a recent clinical trial (Molina JM et al. N Engl J Med. 2015:373[23]2237-2246, Molina JM et al. Abstract presented at: AIDS 2016. http://bit.ly/2aCU1ww). Unlike the common situation, whereby medications are often found to be less efficacious outside of placebo-controlled clinical trials, PrEP seems to be more effective in open-label studies, presumably because adherence is better. Additional reports on new approaches to PrEP included the use of injectable, long-acting medications, such as the investigational HIV integrase inhibitor cabotegravir (http://bit.ly/2aDwooO), and the investigational dapivirine vaginal ring that can be left in place for a month at a time (Brown E et al. Abstract presented at: AIDS 2016. http://bit.ly/2aCVa7f).
PrEP programs are expanding globally, from France and Australia to Kenya and South Africa. By 2020, UNAIDS has set a goal of reaching 3 million people with PrEP. However, PrEP remains expensive—about $13 000 per year in the United States, although some insurance plans may cover the cost. A study reported in Durban showed that 79 684 unique individuals in the United States had started PrEP with TDF/emtricitabine by the end of 2015, about three-quarters of whom were men (Mera R et al. Abstract presented at: AIDS 2016. http://bit.ly/2b3BJHt; http://bit.ly/2bg0S1r). Year-to-year increases in PrEP use are rapid; from 6210 new unique users in 2012 to 42 545 in 2015. Massachusetts, New York, and Illinois have the highest rates of PrEP use on a population basis. However, in states where the lifetime risk of HIV infection is higher, such as those in the South, the rates are lower. White individuals are overrepresented among PrEP users compared with black and Hispanic individuals, who are at higher risk of acquiring HIV.
HOPE FOR A VACCINE
Given the scientific challenges of developing an effective AIDS vaccine, a realistic goal is an investigational regimen that is promising enough to be tested in a large trial. Later this year, the first HIV vaccine efficacy study to launch in more than a decade is slated to begin in South Africa. The phase 3 study will build on an earlier trial demonstrating the modest protective effect of an investigational vaccine tested in Thailand (Rerks-Ngarm S et al. N Engl J Med. 2009;361[23]:2209-2220).
Known as HIV Vaccine Trials Network study 702 (HVTN 702), the trial plans to enroll 5400 healthy men and women and will be conducted from November 2016 to December 2020. The trial will test the efficacy of a combination of 2 experimental vaccines that have been modified from those tested in Thailand to be specific to HIV subtype C predominant in southern Africa (http://bit.ly/2b6kmFx). The first is an injection of a canary pox vector expressing subtype C-specific HIV genes (ALVAC-HIV, provided by Sanofi Pasteur). This vaccine will be followed by booster injections of a bivalent gp120 protein subunit vaccine combined with an adjuvant different from that used in Thailand—known as MF59—to boost the body's immune response (both provided by GSK). Participants will receive a total of 5 injections over 1 year (http://bit.ly/2aCorNp). Interim immunology results from a preliminary study (HVTN 100), presented in Durban, provided sufficient evidence to support implementing the new efficacy trial (Bekker L-G et al. Abstract presented at: AIDS 2016. http://bit.ly/29VL6W2).
Absent a licensed AIDS vaccine, the best strategy for controlling the HIV pandemic remains a combination of treatment and prevention. Ending the epidemic remains far more difficult than deploying effective treatments and minimizing the risk of HIV transmission. The question now is whether the remarkable progress against HIV/AIDS since 2000 will accelerate or stall.
JAMA
