Elsevier

The Lancet

Volume 384, Issue 9939, 19–25 July 2014, Pages 258-271
The Lancet

Seminar
HIV infection: epidemiology, pathogenesis, treatment, and prevention

https://doi.org/10.1016/S0140-6736(14)60164-1Get rights and content

Summary

HIV prevalence is increasing worldwide because people on antiretroviral therapy are living longer, although new infections decreased from 3·3 million in 2002, to 2·3 million in 2012. Global AIDS-related deaths peaked at 2·3 million in 2005, and decreased to 1·6 million by 2012. An estimated 9·7 million people in low-income and middle-income countries had started antiretroviral therapy by 2012. New insights into the mechanisms of latent infection and the importance of reservoirs of infection might eventually lead to a cure. The role of immune activation in the pathogenesis of non-AIDS clinical events (major causes of morbidity and mortality in people on antiretroviral therapy) is receiving increased recognition. Breakthroughs in the prevention of HIV important to public health include male medical circumcision, antiretrovirals to prevent mother-to-child transmission, antiretroviral therapy in people with HIV to prevent transmission, and antiretrovirals for pre-exposure prophylaxis. Research into other prevention interventions, notably vaccines and vaginal microbicides, is in progress.

Section snippets

Epidemiology

The HIV epidemic arose after zoonotic infections with simian immunodeficiency viruses from African primates; bushmeat hunters were probably the first group to be infected with HIV.1 HIV-1 was transmitted from apes and HIV-2 from sooty mangabey monkeys.1 Four groups of HIV-1 exist and represent three separate transmission events from chimpanzees (M, N, and O), and one from gorillas (P). Groups N, O, and P are restricted to west Africa. Group M, which is the cause of the global HIV pandemic,

HIV-1 transmission

The most important factor that increases the risk of sexual transmission of HIV-1 is the number of copies per mL of plasma HIV-1 RNA (viral load), with a 2·4 times increased risk of sexual transmission for every 1 log10 increase.19 Acute HIV infection, which causes very high plasma viral loads in the first few months, is an important driver of HIV epidemics.20 A reduction in plasma viral load of 0·7 log10 is estimated to reduce HIV-1 transmission by 50%.21 Seminal and endocervical viral load

HIV life cycle and host immune responses

Figure 2 shows the virus life cycle. The main target of HIV is activated CD4 T lymphocytes; entry is via interactions with CD4 and the chemokine coreceptors, CCR5 or CXCR4. Other cells bearing CD4 and chemokine receptors are also infected, including resting CD4 T cells, monocytes and macrophages, and dendritic cells. CD4-independent HIV infection of cells can happen, notably in astrocytes37 and renal epithelial cells,38 and subsequent HIV gene expression has an important role in the

Mother-to-child HIV-1 transmission

During the past two decades, remarkable progress has been made in the risk reduction of perinatal HIV-1 transmission. Knowledge about the timing of HIV-1 transmission to infants has allowed the development of appropriate interventions. The risk of HIV-1 transmission to the infant is about 25% at delivery in the absence of interventions, with most of the risk arising after 36 weeks and especially intrapartum.127 HIV-1 transmission happens at a rate of 8·9 per 100 child-years of breastfeeding

Conclusions

HIV continues to be a major contributor to the global burden of disease, especially in sub-Saharan Africa. Antiretroviral therapy is changing the global epidemiology of HIV by increasing prevalence because of reductions in AIDS deaths, and is contributing to decreasing HIV incidence by reduction of the risk of transmission. HIV incidence in men who have sex with men is not decreasing despite high antiretroviral therapy coverage. The drivers of the HIV epidemic in men who have sex with men

Search strategy and selection criteria

We searched PubMed for publications in English from Jan 1, 2008, to Oct 31, 2013, but did not exclude commonly referenced and highly regarded older publications. We used the search terms “HIV” or “AIDS” in combinations with “epidemiology”, “prevention”, “pathogenesis”, “antiretroviral therapy”, “resistance”, and “latency”. We also searched the reference lists of articles identified by this search strategy and selected those we judged relevant. Review articles are cited to provide readers with

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