E p i d e m i o l o g y Without such effort, increases in viral load go undetected, exposing partners to higher risks of transmission.23 With measurement at intervals of 3e12 months, the risk of trans- mission can be reduced further by basing condom use on measurements taken only 3 months before. This guards against the risk of increases in viral load since the last measurement.25 For this reasons, it is important that decisions are not based on viral load measurements taken more than 6 months before. The model used in this paper incorporates more biological realism than earlier work13 14 by using the functional form of the viral loadetransmission relationship that reﬂects a sophisti- cated analysis of observational data,20 explicitly tracking viral load monitoring and modelling the course of viral load evolution over time. Nevertheless, a number of simplifying assumptions were made. The risk of transmission per sex act was scaled to match only an approximate observation of the risk, without considering differences in the frequency of being the insertive or receptive partner.26 27 We assumed that, below a certain viral load level, the chance of transmission is low and not actually zero; but evidence is lacking, since observing almost no instances of transmission15 could be consistent with either possibility. The response of patients to treatment varies widely and we have attempted to only broadly represent this in the model. However, we believe the key features of viral load evolution have been captured by ﬁnding a set of parameters for the viral load trajectory (its rise, period of stability and subsequent rise) and its relationship to treatment adherence. An important limitation of the model is that the effects of other STIs on HIV transmission is not incorporated. The data available from the cohort do not permit a detailed representation of STI transmission and the inﬂuence of STIs would depend on many factors, including the pattern of STI spread across the populations. If STIs were included, the overall estimate of HIV transmission risk would probably be greater, but we would expect the key relationship between risk and patterns of condom use to hold or be strengthened (since more frequent screening affords greater opportunity for treating STIs). Finally, the model does not include the inﬂuence of intermittent viraemia on the chance of HIV transmission, since we assumed its inﬂuence on transmission to be relatively small.28 The implications of this work are that the key message to patients should remain that always using condoms when receiving treatment is the best way to protect partners from the risk of HIV transmission. However, an additional message is that using condoms is most crucial when patients have not recently (within the past 3 months) had an undetectable viral load measurement. This message reﬁnes the intuitive association between successful treatment and reduced transmission24 29 and could substantially improve protection for infected partners. Key messages < Intermittent use of condoms by men receiving treatment offers relatively little reduction in the chance of transmission to their partner. < In contrast, the chance of HIV transmission can be substantially reduced if condoms are used when the last undetectable viral load measurement was not within the past 3 months. < Frequent viral load measurement can maximise the potential for treatment to reduce HIV transmission. 20 This advice must be supported by frequent viral load monitoring (at least every 6 months, but preferably every 3 months) of all patients receiving treatment. Acknowledgements TBH thanks the Wellcome Trust for funding support. We thank two reviewers for their constructive assessment of this work. Funding Wellcome Trust. Competing interests None. Provenance and peer review Not commissioned; externally peer reviewed. REFERENCES 1. Hammer SM, Squires KE, Hughes MD, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeﬁciency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med 1997;337:725e33. 2. Staszewski S, Morales-Ramirez J, Tashima KT, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med 1999;341:1865e73. 3. UNAIDS. Report on the Global AIDS epidemic, http://www.unaids.org/en/ knowledge/HIVdata/globalreport/2008/2008_global_report.asp, 2008. 4. Jahn A, Floyd S, Crampin AC, et al. Population-level effect of HIV on adult mortality and early evidence of reversal after introduction of antiretroviral therapy in Malawi. Lancet 2008;371:1603e11. 5. When To Start Consortium, Sterne JA, May M, Costagliola D, et al. Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies. Lancet 2009;373:1352e63. 6. Montaner JS, Hogg R, Wood E, et al. The case for expanding access to highly active antiretroviral therapy to curb the growth of the HIV epidemic. Lancet 2006;368:531e6. 7. Granich RM, Gilks CF, Dye C, et al. Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet 2009;373:48e57. 8. Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeﬁciency virus type 1. Rakai Project Study Group. N Engl J Med 2000;342:921e9. 9. Vernazza P, Hirschel B, Bernasconi E, et al. Les personnes s´eropositives ne souffrant d’aucune autre MST et suivant un traitement antir´etroviral efﬁcace ne transmettent pas le VIH par voie sexuelle. Bulletin des m´edecins suisses 2008;89:165e9. 10. Vernazza PL. The debate continues: does ‘undetectable’ mean ‘uninfectious’? HIV ther 2009;3:113e16. 11. National Association of People Living With HIV/AIDS 2008. AIDS 2008: The Swiss Statement- the debate continues, 2009. Available at http://napwa.org.au/pl/2008/ 09/aids-2008-the-swiss-statement-the-debate-continues (accessed 29 June 2010). 12. Sturmer M, Doerr HW, Berger A, et al. Is transmission of HIV-1 in non-viraemic serodiscordant couples possible? Antivir Ther 2008;13:729e32. 13. Wilson DP, Law MG, Grulich AE, et al. Relation between HIV viral load and infectiousness: a model-based analysis. Lancet 2008;372:314e20. 14. Garnett GP, Gazzard B. Risk of HIV transmission in discordant couples. Lancet 2008;372:270e1. 15. Attia S, Egger M, Muller M, et al. Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis. Aids 2009;23:1397e404. 16. Wilson DP. Data are lacking for quantifying HIV transmission risk in the presence of effective antiretroviral therapy. Aids 2009;23:1431e3. 17. van Sighem AI, van de Wiel MA, Ghani AC, et al. Mortality and progression to AIDS after starting highly active antiretroviral therapy. Aids 2003;17:2227e36. 18. Hallett TB, Gregson S, Dube S, et al. The impact of monitoring HIV patients prior to treatment in resource-poor settings: insights from mathematical modelling. PLoS Med 2008;5:e53. 19. Smit C, Hallett TB, Lange J, et al. Late entry to HIV care limits the impact of anti- retroviral therapy in The Netherlands. PLoS One 2008;3:e1949. 20. Fraser C, Hollingsworth TD, Chapman R, et al. Variation in HIV-1 set-point viral load: epidemiological analysis and an evolutionary hypothesis. Proc Natl Acad Sci U S A 2007;104:17441e6. 21. Braithwaite RS, Justice AC, Chang CC, et al. Estimating the proportion of patients infected with HIV who will die of comorbid diseases. Am J Med 2005;118:890e8. 22. Centers for Disease Control and Prevention. http://www.cdc.gov/hiv/, 2008. 23. Ndiaye B, Ould-Kaci K, Salleron J, et al. Characteristics of and outcomes in HIV-infected patients who return to care after loss to follow-up. AIDS 2009;23:1786e9. 24. Stolte IG, de Wit JB, van EA, et al. Perceived viral load, but not actual HIV-1-RNA load, is associated with sexual risk behaviour among HIV-infected homosexual men. AIDS 2004;18:1943e9. 25. Hirschel B. Meal. How reliable is an undetectable viral load (VL)? The past as a guide to the future. XVII International AIDS conference. Mexico City: 2008. Sex Transm Infect 2011;87:17e21. doi:10.1136/sti.2010.042622