The fourth HIV epidemic

Gabrièle Laborde-Balen, Bernard Taverne, Cheikh Tidiane Ndour, Charles Kouanfack, Martine Peeters, Ibra Ndoye, Eric Delaporte

In The Lancet Infectious Diseases, Ravindra Gupta and colleagues1 present alarming results on the development of pre-treatment viral resistance to the most commonly used drugs to treat HIV infection in resource-limited countries. These findings complete the bleak picture of antiretroviral (ARV) treatment failure that is gradually emerging in these countries. An increase in virological failure rates among adults has been reported in Africa, ranging from 5% to 31% after 12 months and up to 38% beyond 48 months of treatment.2

The onset of virological failure has multiple causes: treatment non-adherence, use of ARVs with weak genetic barriers, exposure to ARVs through prevention of mother-to-child transmission, to name a few. Treatment failure underscores the limitations of health-care systems while also revealing inequalities between countries. In resource-limited countries, high costs hinder access to second-line and especially third-line molecules, whereas WHO recommends introduction of new molecules with high genetic barriers.3 These inequalities are further exacerbated by weak social protection systems. In 2017, WHO noted rapid development of viral resistance to ARVs. Its 2017–21 action plan recommends switching treatment regimens, widespread virological follow-up, better support systems for adherence, and resistance surveillance at a country level.3

In 1987, Jonathan Mann, Director of the WHO Special Programme on AIDS, declared before the UN General Assembly that the HIV pandemic comprised three epidemics: the first was the worldwide spread of the virus; the second was the AIDS disease itself; and the third was the social, economic, cultural, and political response to the first two epidemics—particularly the discrimination against infected people.4 Nearly 30 years later, widespread access to ARV medicines and decreased mortality have successfully limited the first two epidemics, while the third remains a major issue. The wave of ARV treatment failure primarily affecting resource-limited countries should be considered a fourth epidemic.

This fourth epidemic, accompanied by the emergence of viral resistance to ARV drugs, could affect 3–5 million people between 2020 and 2030.5 It should therefore be considered as a specific occurrence, stemming from the failures or limitations of public health strategies and systems implemented so far. Overcoming the fourth epidemic requires not only more new drugs but also state-level commitment and international support for country-specific public health intervention plans. Achieving the UNAIDS ambitious goal to eradicate the HIV epidemic worldwide by 2030 will depend on effectively controlling this fourth epidemic.

We acknowledge Sharon Calandra who translated the article and edited the final version. We declare no competing interests.



1 Gupta, RK, Gregson, J, Parkin, N et al. HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis. (published online Nov 30.)Lancet Infect Dis. 2017;
2 Boender, TS, Sigaloff, KCE, McMahon, JH et al. Long-term virological outcomes of first-line antiretroviral therapy for HIV-1 in low- and middle-income countries: a systematic review and meta-analysis. Clin Infect Dis. 2015; 61: 1453–1461
3 WHO. Global action plan on HIV drug resistance 2017–2021. World Health Organization, Geneva; 2017
4 Mann, J. Statement at an informal briefing on AIDS to the 42nd Session of the United Nations General Assembly on Tuesday, Oct 20, 1987. World Health Organization, Geneva; 1987
5 Estill, J, Ford, N, Salazar-Vizcaya, L et al. The need for second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030: a mathematical modelling study. Lancet HIV. 2016; 3: e132–e139

The Lancet Infectious Diseases
pre-treatment viral resistance, drug resistance, treatment failure, virological failure