How important is the acute phase in HIV epidemiology

At present, the best hope for eliminating HIV transmission and bringing the epidemic of HIV to an end lies in the use of anti-retroviral therapy for prevention, a strategy referred to variously as Test and Treat (T&T), Treatment as Prevention (TasP) or Treatment centred Prevention (TcP). One of the key objections to the use of T&T to stop transmission concerns the role of the acute phase in HIV transmission. The acute phase of infection lasts for one to three months after HIV-seroconversion during which time the risk of transmission may be ten to twenty times higher, per sexual encounter, than it is during the chronic phase which lasts for the next ten years. Regular testing for HIV is more likely to miss people who are in the acute phase than in the chronic phase and it is essential to determine the extent to which this might compromise the impact of T&T on HIV-transmission. Here we show that 1) provided the initial epidemic doubling time is about 1.0 to 1.5 years, as observed in South Africa, random testing with an average test interval of one year will still bring the epidemic close to elimination even if the acute phase lasts for 3 months during which time transmission is 26 times higher than in the chronic phase; 2) testing people regularly at yearly intervals is significantly more effective then testing them randomly; 3) testing people regularly at six monthly intervals and starting them on ART immediately, will almost certainly guarantee elimination. In general it seems unlikely that elevated transmission during the acute phase is likely to change predictions of the impact of treatment on transmission significantly. Other factors, in particular age structure, the structure of sexual networks and variation in set-point viral load are likely to be more important and should be given priority in further analyses.

[1]  J. Mullins,et al.  Genital HIV-1 RNA Predicts Risk of Heterosexual HIV-1 Transmission , 2011, Science Translational Medicine.

[2]  James P. Hughes,et al.  Estimating the Impact of Plasma HIV-1 RNA Reductions on Heterosexual HIV-1 Transmission Risk , 2010, PloS one.

[3]  Connie Celum,et al.  Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis , 2010, The Lancet.

[4]  Matthias Egger,et al.  Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis , 2009, AIDS.

[5]  Christophe Fraser,et al.  HIV-1 transmission, by stage of infection. , 2008, The Journal of infectious diseases.

[6]  Matthew G Law,et al.  Relation between HIV viral load and infectiousness: a model-based analysis , 2008, The Lancet.

[7]  C. Dye,et al.  HIV infection, antiretroviral therapy, and CD4+ cell count distributions in African populations. , 2006, The Journal of infectious diseases.

[8]  O. Laeyendecker,et al.  Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. , 2005, The Journal of infectious diseases.

[9]  Michael P Busch,et al.  Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection , 2003, AIDS.

[10]  E. Gouws,et al.  The epidemiology of human immunodeficiency virus in South Africa. , 2001, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[11]  S. Vermund,et al.  Virologic and immunologic determinants of heterosexual transmission of human immunodeficiency virus type 1 in Africa. , 2001, AIDS research and human retroviruses.

[12]  J J Goedert,et al.  A simple relationship between viral load and survival time in HIV-1 infection. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[13]  L. Kalish,et al.  Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Infants Transmission Study Group. , 1999, The New England journal of medicine.