Estimating the public health impact of the effect of herpes simplex virus suppressive therapy on plasma HIV-1 viral load.
OBJECTIVE
Trials of herpes simplex virus (HSV) suppressive therapy among HSV-2/HIV-1-infected individuals have reported an impact on plasma HIV-1 viral loads (PVLs). Our aim was to estimate the population-level impact of suppressive therapy on female-to-male HIV-1 sexual transmission.


METHODS
By comparing prerandomization and postrandomization individual-level PVL data from the first two HSV suppressive therapy randomized controlled trials in sub-Saharan Africa, we estimated the effect of treatment on duration of asymptomatic infection and number of HIV-1 transmission events for each trial.


RESULTS
Assuming that a reduction in PVL is accompanied by an increased duration of HIV-1 asymptomatic infection, 4-6 years of HSV suppressive therapy produce a 1-year increase in the duration of this stage. To avert one HIV-1 transmission requires 8.8 [95% confidence interval (CI), 5.9-14.9] and 11.4 (95% CI, 7.8-27.5) women to be treated from halfway through their HIV-1 asymptomatic period, using results from Burkina Faso and South African trials, respectively. Regardless of the timing of treatment initiation, 51.6 (95% CI, 30.4-137.0) and 66.5 (95% CI, 36.7-222.6) treatment-years are required to avert one HIV-1 infection. Distributions of set-point PVL values from sub-Saharan African populations suggest that unintended adverse consequences of therapy at the population level (i.e. increased HIV-1 transmission due to increased duration of infection) are unlikely to occur in these settings.


CONCLUSIONS
HSV suppressive therapy may avert relatively few HIV-1 transmission events per person-year of treatment. Its use as a prevention intervention may be limited; however, further research into its effect on rate of CD4 cell count decline and the impact of higher dosing schedules is warranted.
Baggaley
Rebecca F
RF
MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK. r.baggaley@imperial.ac.uk
Griffin
Jamie T
JT
Chapman
Ruth
R
Hollingsworth
T Déirdre
TD
Nagot
Nicolas
N
Delany
Sinead
S
Mayaud
Philippe
P
de Wolf
Frank
F
Fraser
Christophe
C
Ghani
Azra C
AC
Weiss
Helen A
HA
D017954:Africa South of the Sahara / Q000453:epidemiology; D000998:Antiviral Agents / Q000494:pharmacology*; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects; D006558:Herpes Genitalis / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D008297:Male; D011634:Public Health; D012367:RNA, Viral / Q000097:blood
D000998:Antiviral Agents; D012367:RNA, Viral