Limits...
Genital herpes has played a more important role than any other sexually transmitted infection in driving HIV prevalence in Africa.

Abu-Raddad LJ, Magaret AS, Celum C, Wald A, Longini IM, Self SG, Corey L - PLoS ONE (2008)

Bottom Line: The nature of the epidemiologic synergy was explored qualitatively and quantitatively and compared to other sexually transmitted infections (STIs).The results suggest a more substantial role for HSV-2 in fueling HIV spread in sub-Saharan Africa than other STIs.This finding suggests that prevention of HSV-2 infection through a prophylactic vaccine may be an effective intervention both in nascent epidemics with high HIV incidence in the high risk groups, and in established epidemics where a large portion of HIV transmission occurs in stable partnerships.

View Article: PubMed Central - PubMed

Affiliation: Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. laith@scharp.org

ABSTRACT

Background: Extensive evidence from observational studies suggests a role for genital herpes in the HIV epidemic. A number of herpes vaccines are under development and several trials of the efficacy of HSV-2 treatment with acyclovir in reducing HIV acquisition, transmission, and disease progression have just reported their results or will report their results in the next year. The potential impact of these interventions requires a quantitative assessment of the magnitude of the synergy between HIV and HSV-2 at the population level.

Methods and findings: A deterministic compartmental model of HIV and HSV-2 dynamics and interactions was constructed. The nature of the epidemiologic synergy was explored qualitatively and quantitatively and compared to other sexually transmitted infections (STIs). The results suggest a more substantial role for HSV-2 in fueling HIV spread in sub-Saharan Africa than other STIs. We estimate that in settings of high HSV-2 prevalence, such as Kisumu, Kenya, more than a quarter of incident HIV infections may have been attributed directly to HSV-2. HSV-2 has also contributed considerably to the onward transmission of HIV by increasing the pool of HIV positive persons in the population and may explain one-third of the differential HIV prevalence among the cities of the Four City study. Conversely, we estimate that HIV had only a small net impact on HSV-2 prevalence.

Conclusions: HSV-2 role as a biological cofactor in HIV acquisition and transmission may have contributed substantially to HIV particularly by facilitating HIV spread among the low-risk population with stable long-term sexual partnerships. This finding suggests that prevention of HSV-2 infection through a prophylactic vaccine may be an effective intervention both in nascent epidemics with high HIV incidence in the high risk groups, and in established epidemics where a large portion of HIV transmission occurs in stable partnerships.

Show MeSH

Related in: MedlinePlus

Time course of the HIV epidemic in Kisumu, Kenya.As in Figure 1, but now assuming PECAcq = 9 (implying RR = 2.9 [23]).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2377333&req=5

pone-0002230-g002: Time course of the HIV epidemic in Kisumu, Kenya.As in Figure 1, but now assuming PECAcq = 9 (implying RR = 2.9 [23]).

Mentions: The parameter values of the model are chosen according to the best available empirical evidence of the biology, epidemiology, and interaction of the two infections. In particular, this is the first modeling assessment where the recently established detailed empirical data about the pattern of HSV-2 reactivation in its clinical and subclinical form has played a central role in the model. Table 2 lists the key assumptions of the model. The per-exposure cofactor provides the multiplicative impact of a given risk on HIV transmission probability per coital act. The susceptibility enhancement per-exposure cofactor of PECAcq = 4 and PECAcq = 9 during HSV-2 primary infection and reactivations (i.e. HSV-2 shedding), irrespective of whether HSV-2 infection is manifested clinically or subclinically, are derived in Protocol S2 from the overall risk ratios (RR) of HIV acquisition in HSV-2 seropositive persons as estimated in two meta-analyses at RR values of 2.1 [24] and 2.9 [23], respectively. We assume an infectivity enhancement per-exposure cofactor of PECTrans = 3 in dually infected persons during HSV-2 primary infection and reactivations irrespective of clinical symptoms as a representative value of the combined effect of HSV-2 induced increase in HIV transcription [27], [28], [29], [30], [31], the measured heightened HIV plasma viral load in dually infected patients [33], [34], [35], [46], [47], [48] (and its implication in terms of HIV infectiousness [36]), and the presence of HIV-1 RNA in herpetic lesions [32]. Protocol S2 includes more discussion of the rationale for this value. We hypothesize that the enhanced susceptibility and infectivity do not occur in absence of HSV-2 shedding in view of the lack of a plausible biological mechanism during HSV-2 latency.


Genital herpes has played a more important role than any other sexually transmitted infection in driving HIV prevalence in Africa.

Abu-Raddad LJ, Magaret AS, Celum C, Wald A, Longini IM, Self SG, Corey L - PLoS ONE (2008)

Time course of the HIV epidemic in Kisumu, Kenya.As in Figure 1, but now assuming PECAcq = 9 (implying RR = 2.9 [23]).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2377333&req=5

pone-0002230-g002: Time course of the HIV epidemic in Kisumu, Kenya.As in Figure 1, but now assuming PECAcq = 9 (implying RR = 2.9 [23]).
Mentions: The parameter values of the model are chosen according to the best available empirical evidence of the biology, epidemiology, and interaction of the two infections. In particular, this is the first modeling assessment where the recently established detailed empirical data about the pattern of HSV-2 reactivation in its clinical and subclinical form has played a central role in the model. Table 2 lists the key assumptions of the model. The per-exposure cofactor provides the multiplicative impact of a given risk on HIV transmission probability per coital act. The susceptibility enhancement per-exposure cofactor of PECAcq = 4 and PECAcq = 9 during HSV-2 primary infection and reactivations (i.e. HSV-2 shedding), irrespective of whether HSV-2 infection is manifested clinically or subclinically, are derived in Protocol S2 from the overall risk ratios (RR) of HIV acquisition in HSV-2 seropositive persons as estimated in two meta-analyses at RR values of 2.1 [24] and 2.9 [23], respectively. We assume an infectivity enhancement per-exposure cofactor of PECTrans = 3 in dually infected persons during HSV-2 primary infection and reactivations irrespective of clinical symptoms as a representative value of the combined effect of HSV-2 induced increase in HIV transcription [27], [28], [29], [30], [31], the measured heightened HIV plasma viral load in dually infected patients [33], [34], [35], [46], [47], [48] (and its implication in terms of HIV infectiousness [36]), and the presence of HIV-1 RNA in herpetic lesions [32]. Protocol S2 includes more discussion of the rationale for this value. We hypothesize that the enhanced susceptibility and infectivity do not occur in absence of HSV-2 shedding in view of the lack of a plausible biological mechanism during HSV-2 latency.

Bottom Line: The nature of the epidemiologic synergy was explored qualitatively and quantitatively and compared to other sexually transmitted infections (STIs).The results suggest a more substantial role for HSV-2 in fueling HIV spread in sub-Saharan Africa than other STIs.This finding suggests that prevention of HSV-2 infection through a prophylactic vaccine may be an effective intervention both in nascent epidemics with high HIV incidence in the high risk groups, and in established epidemics where a large portion of HIV transmission occurs in stable partnerships.

View Article: PubMed Central - PubMed

Affiliation: Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. laith@scharp.org

ABSTRACT

Background: Extensive evidence from observational studies suggests a role for genital herpes in the HIV epidemic. A number of herpes vaccines are under development and several trials of the efficacy of HSV-2 treatment with acyclovir in reducing HIV acquisition, transmission, and disease progression have just reported their results or will report their results in the next year. The potential impact of these interventions requires a quantitative assessment of the magnitude of the synergy between HIV and HSV-2 at the population level.

Methods and findings: A deterministic compartmental model of HIV and HSV-2 dynamics and interactions was constructed. The nature of the epidemiologic synergy was explored qualitatively and quantitatively and compared to other sexually transmitted infections (STIs). The results suggest a more substantial role for HSV-2 in fueling HIV spread in sub-Saharan Africa than other STIs. We estimate that in settings of high HSV-2 prevalence, such as Kisumu, Kenya, more than a quarter of incident HIV infections may have been attributed directly to HSV-2. HSV-2 has also contributed considerably to the onward transmission of HIV by increasing the pool of HIV positive persons in the population and may explain one-third of the differential HIV prevalence among the cities of the Four City study. Conversely, we estimate that HIV had only a small net impact on HSV-2 prevalence.

Conclusions: HSV-2 role as a biological cofactor in HIV acquisition and transmission may have contributed substantially to HIV particularly by facilitating HIV spread among the low-risk population with stable long-term sexual partnerships. This finding suggests that prevention of HSV-2 infection through a prophylactic vaccine may be an effective intervention both in nascent epidemics with high HIV incidence in the high risk groups, and in established epidemics where a large portion of HIV transmission occurs in stable partnerships.

Show MeSH
Related in: MedlinePlus