Using a mathematical modeling approach, this study estimated the per-sex-act and per-partnership FtoMTPs of HIV and HSV-2 among a cohort of young males in South Africa. It suggested that HSV-2 infection enhanced HIV acquisition and conversely, that HIV infection could enhance HSV-2 acquisition. Furthermore, this study provided evidence of a protective effect of MC on HSV-2 acquisition by young males.
This study has some limitations: a) we used data obtained among men aged 18 to 24, recruited for a MC trial and thus not representative of the general male population; b) condom use was collected by partnership. Thus, condom use per sex act was not directly available and had to be extrapolated; c) we cannot exclude some bias since the HIV and HSV-2 serostatuses of the female partners of each male were not directly assessed but estimated. Nevertheless, in estimating the males’ exposure to these two viruses for each of their sexual partnerships, we were careful to take into account the age of their female partners and the sexual behavior by age of the females of the same community; d) we also cannot exclude bias due to misreporting of sexual behavior of males and females. However, this limitation is inherent to all studies of this type.
Our estimation of HIV FtoMTP per sex act is consistent with recent values obtained by a meta-analysis of transmission studies conducted in developing countries [11
]. In particular it is consistent with the results of a recent HIV-1 per-sex-act FtoMTP estimation conducted in a Kenyan prospective cohort study in the context of multiple partnerships [10
]. In contrast, our estimation of HSV-2 FtoMTP per sex act is higher than the comparable published values obtained in two studies conducted among discordant couples, mostly in developed countries [5
]. Several factors may explain this difference [5
]. Using discordant couples can create a selection bias for two reasons: a) couples having a low average FtoMTP are more likely to be discordant, b) people engaged in long-term relationships have a lower FtoMTP because HSV-2 transmission decreases as a function of the duration of the partnership [6
This study was conducted among young men who are for the most part unmarried or not living as married. The short duration of their partnerships and the low number of sexual contacts [19
] may explain why per-partnership FtoMTPs were only about 4 times higher than the corresponding per-sex-act FtoMTPs for HIV and HSV-2.
In this study, which used a mathematical modeling approach, the ITT and as-treated (AT) protective effect of MC on the per-sex-act and per-partnership FtoMTPs of HIV were almost identical to the reducing effect of MC on HIV incidence estimated using a statistical approach and the same dataset [19
In both ITT and AT analyses, we observed a reducing effect of MC on HSV-2 acquisition by males, which was significant for the AT analysis. This effect was estimated by ensuring that the effect of MC on HIV and the effect of HIV on HSV-2 were taken into account. The difference between ITT and AT analyses may be partly due to the diluting effect of crossovers. This reducing effect of MC on HSV-2 acquisition is consistent with the conclusions of a meta-analysis [22
] and the results of the Rakai MC trial [24
]. It provides additional evidence supporting the promotion of MC in Africa as a method to reduce the spread of STIs such as HIV and HSV-2. This effect should be further investigated by pooling the results of the three circumcision randomized trials.
We found a significant reducing effect of reported condom use on the per-partnership FtoMTPs of HIV and HSV-2. The fact that condom use per sex act was extrapolated in addition to its possible misreporting may have contributed to the large confidence intervals found for the effect of reported condom use on the per-sex-act FtoMTPs of HIV and HSV-2.
The significant enhancing effect of male or female HSV-2 positive status on the FtoMTP of HIV, as shown in this study and in many others, is now well accepted [1
]. This study showed a significant enhancing effect of HIV status on the FtoMTP of HSV-2. Such an effect could be due to transient immunosuppression during the acute stage of HIV infection which may increase HSV-2 acquisition and/or increase HSV-2 infectiousness among HIV-infected females. It should be further investigated.
The findings of this study confirm and reinforce the interpretation of a multisite study which found that sexual behavior and prevalence levels of MC and HSV-2 were key factors in understanding the heterogeneity of the HIV epidemic in Africa [31
]. It appears that the interactions between HIV, HSV-2, sexual behavior and MC should all be taken into account to understand the heterogeneity of the HIV and HSV-2 epidemics in Africa.
Studying the FtoMTPs of both HIV and HSV-2, we found that cofactors such as MC and the presence of the other virus had a strong effect on these FtoMTPs. Hence, it is important for transmission studies to carefully take into account these cofactors, in order to obtain comparable results independent of the prevalence of these cofactors in the study population.
The results of this study are consistent with our current knowledge of the epidemiology of HSV-2 in Africa and the synergy between the HIV and HSV-2 epidemics in this part of the world. The fact that HSV-2 treatment (acyclovir 400 mg twice daily) does not prevent HIV acquisition [33
], most likely because the current HSV-2 treatment does not eradicate HSV-2, does not disprove the facilitating effect of HSV-2 on HIV acquisition. In addition to the reducing effect of MC on HIV acquisition by males, the effect of MC on HSV-2 is another argument in favor of the roll-out of MC in African countries where most males are uncircumcised [34
]. Modeling studies are needed to better understand the interactions between HIV, HSV-2, MC, sexual behavior including condom use, not only in the short term, as studied by randomized controlled trials, but also in the long term.