Proportion of new HIV infections attributable to herpes simplex 2 increases over time: simulations of the changing role of sexually transmitted infections in sub-Saharan African HIV epidemics

Freeman, Esther E.; Orroth, Kate K.; White, Richard G.; Glynn, Judith R.; Bakker, Roel; Boily, Marie‐Claude; Habbema, Dik; Buvé, Anne; Hayes, Richard

doi:10.1136/sti.2006.023549

Cited by 100 publications

(99 citation statements)

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“…In the United States, HSV-2 seropositivity is higher among women (23.1%) than men (11.2%) (45). These studies suggest that interventions against HSV-2 may have a key role in HIV prevention (18).…”

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confidence: 82%

Simultaneous Delivery of Tenofovir and Acyclovir via an Intravaginal Ring

Moss

Malone

Smith

et al. 2012

Antimicrob Agents Chemother

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Vaginal microbicides may play an important role in protecting women from HIV infection. A strong synergy between HSV and HIV has been observed, and epidemiological studies demonstrate that HSV infection increases the risk of HIV acquisition. Incorporation of the antiretroviral tenofovir (TFV) along with the antiherpetic acyclovir (ACV) into combination intravaginal rings (IVRs) for sustained mucosal delivery of both compounds could lead to increased microbicide product adherence and efficacy compared with conventional vaginal formulations. A novel, dual-protection "pod IVR" platform developed in-house and delivering ACV and TFV was evaluated in rabbit and sheep models. The devices were safe and exhibited sustained release of both drugs independently and at controlled rates over the 28-day studies. Daily release rates were estimated based on residual drug content of the used devices: rabbits, 343 ؎ 335 g day ؊1 (ACV) and 321 ؎ 207 g day ؊1 (TFV); sheep, 174 ؎ 14 g day ؊1 (ACV) and 185 ؎ 34 g day ؊1 (TFV). Mean drug levels in sheep vaginal samples were as follows: secretions, 5.25 ؎ 7.31 g ml ؊1 (ACV) and 20.6 ؎ 16.2 g ml ؊1 (TFV); cervicovaginal lavage fluid, 118 ؎ 113 ng ml ؊1 (ACV) and 191 ؎ 125 ng ml ؊1 (TFV); tissue, 173 ng g ؊1 (ACV) and 93 ng g ؊1 (TFV). An in vitro-in vivo correlation was established for both drugs and will allow the development of future formulations delivering target levels for prophylaxis and therapy. These data suggest that the IVR based on the pod design has potential in the prevention of transmission of HIV-1 and other sexually transmitted pathogens. Significant progress has been achieved in providing increased access to HIV/AIDS services in several low-and middleincome countries (44). Despite these encouraging findings, women in the developing world remain disproportionately at risk of HIV infection. Seventy-six percent of new HIV infections in sub-Saharan Africa occur in women aged 15 to 24 years (42). The proportion is as high as 90% in South Africa (38). In the absence of a preventative vaccine, effective prophylactic biomedical technologies are urgently required. Campaigns aimed at encouraging monogamy and condom use have had limited success in areas where marriage has been identified as the major risk factor for HIV acquisition in women (3,15,16,21,25).Human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 2 (HSV-2), the serotype most commonly associated with genital herpes, are responsible for two intersecting epidemics, where the disease caused by one virus facilitates the transmission of and pathogenesis by the other. A strong synergy between HSV and HIV has been observed, and epidemiological studies demonstrate that HSV infection increases the risk of HIV-1 acquisition (33,34,43). A meta-analysis found that prevalent HSV-2 infection is associated with a threefold-increased risk of HIV acquisition among both men and women. These results suggest that, in areas of high HSV-2 prevalence, a substantial proportion of HIV infection is linked to HSV-2 infection (...

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confidence: 82%

Simultaneous Delivery of Tenofovir and Acyclovir via an Intravaginal Ring

Moss

Malone

Smith

et al. 2012

Antimicrob Agents Chemother

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“…51,52 While the search for an effective prophylactic HIV vaccine continues, protection against sexually transmitted diseases (such as HSV) may also help prevent the spread of HIV infection among women. 53,54 …”

Section: Resultsmentioning

confidence: 99%

Women and vaccinations: From smallpox to the future, a tribute to a partnership benefiting humanity for over 200 years

Datta¹,

Bhatla²,

Burgess³

et al. 2009

Human Vaccines

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perceived to be the main beneficiaries of vaccination. However, even when vaccines are given exclusively to children, herd effect often renders benefit to other segments of society. [2][3][4] Not often is it realized that women have had a close association with vaccines from their advent. They have been key players in the development and implementation of vaccines and, in return, have been major beneficiaries of their use. This article is a compilation of views from experts in vaccinology and women's health examining this unique association. The Role of Women in the Early History of VaccinationPrior to its eradication by vaccination 30 years ago, smallpox was a major public health problem. In the late 18 th century Edward Jenner, an English country physician, realized that while many of his patients bore the scars of smallpox, one group had unblemished skin. These were the milkmaids. Realizing that most of these women had previously suffered from cowpox he inferred that the widely held local belief that cowpox infection rendered protection against smallpox was indeed likely to be valid and extrapolated that this protection may be extended to other individuals if exposed to cowpox. 5 Jenner subsequently inoculated a young boy (James Phipps) with cowpox and, to his satisfaction, found him protected against smallpox (Fig. 1), publishing his findings in 1798. 6 Indeed, the word vaccine is derived from vaccinia (or cowpox), which subsequently protected the recipient from variola (or smallpox). 5 While this landmark discovery is well documented and Jenner's genius widely commended, women played two important and under-appreciated roles. Firstly the excellent cooperation of milkmaids made Jenner's investigations possible. Secondly, one of their number (Sarah Nelms), who was suffering from cowpox at the time, volunteered a lesion on her arm as a source for the inoculum used on the boy. 5 Sarah Nelms established a precedent-other women and girls have since also provided the seed for new vaccines. For example, the Jeryl-Lynn mumps vaccine strain, now established globally as the safest mumps vaccine, was derived some decades ago from a mumps infection of a young girl of the same name. 7,8 Interestingly, in Western countries, a woman pioneered the concept of protection from infectious disease via asymptomatic exposure to an infectious agent even prior to the advent of vaccination. Before Jenner's publication in 1798, the approach most widely used Vaccines have rewarded women handsomely in return. Individual women benefit in many ways ranging from safer pregnancies to preventing cancers to attractive, unblemished skin. Some vaccines are even specifically designed to prevent diseases primarily affecting women such as cervical cancer.Vaccines also have offered societal benefits to women. These include better maternal health and fostering an environment more amenable to effective family planning. With these advances, women become more empowered and have access to better economic opportunities.The challenge of meeting the millen...

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“…Subsequent modelling studies have suggested that throughout HIV epidemics in Africa, the contribution of STIs to HIV transmission may remain high, with 50% or more of HIV transmission attributed to STIs [79]. However, this relative stability in the overall population attributable fraction (PAF) conceals opposing trends in the contribution of curable and incurable STIs.…”

Section: Discussionmentioning

confidence: 99%

“…However, this relative stability in the overall population attributable fraction (PAF) conceals opposing trends in the contribution of curable and incurable STIs. The attributable-fraction for curable STIs is predicted to fall during HIV epidemics, while the attributable-fraction for HSV-2 is predicted to rise [79].…”

Section: Discussionmentioning

confidence: 99%

Curable Sexually Transmitted Infection Treatment Interventions to Prevent HIV Transmission in Sub-Saharan Africa

White¹

2009

TOIDJ

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Abstract:Introduction: Sub-Saharan Africa (Africa) remains the most severely HIV affected region in the world. As there will not be a cure or vaccine against HIV for many years, primary HIV prevention remains key to HIV control. Primary prevention currently includes treatment of curable sexually transmitted infections (STIs). Here, the evidence for curable STI treatment as an HIV prevention strategy in Africa is reviewed.Results: Despite data on the plausible biological mechanisms from laboratory studies and the relative risks from epidemiological studies suggesting that classical STIs do increase the risk of HIV acquisition and transmission, the impact of curable STI treatment on HIV transmission measured in RCTs has varied markedly. Syndromic STI treatment was shown to be an effective strategy in a population with an early HIV epidemic, but neither syndromic STI treatment, nor mass STI treatment were effective in mature HIV epidemics. Among sex workers with relatively low rates of STI, presumptive STI treatment also failed to reduce HIV incidence.Discussion: Rational health policy requires that scarce resources be allocated to interventions with the best costeffectiveness even if relative impact at population level is modest. Curable STI treatment is likely to prevent a decreasing fraction of new HIV infections as the HIV epidemic expands, but, because of increasing HIV incidence it may remain cost-effective for HIV prevention in many African countries.

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Proportion of new HIV infections attributable to herpes simplex 2 increases over time: simulations of the changing role of sexually transmitted infections in sub-Saharan African HIV epidemics

Cited by 100 publications

References 39 publications

Simultaneous Delivery of Tenofovir and Acyclovir via an Intravaginal Ring

Simultaneous Delivery of Tenofovir and Acyclovir via an Intravaginal Ring

Women and vaccinations: From smallpox to the future, a tribute to a partnership benefiting humanity for over 200 years

Curable Sexually Transmitted Infection Treatment Interventions to Prevent HIV Transmission in Sub-Saharan Africa

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