The magnitude of the global human immunodeficiency virus (HIV) epidemic is determined by women from lower income countries, specifically sub-Saharan Africa. Microbicides offer women who are unable to negotiate safe sex practices a self-initiated HIV prevention method. Of note, is its potential to yield significant public health benefits even with relatively conservative efficacy, coverage and user adherence estimates, making microbicides an effective intervention to invest scarce healthcare resources. Existing healthcare delivery systems provide an excellent opportunity to identify women at highest risk for infection and to also provide an access point to initiate microbicide use. Innovative quality improvement approaches, which strengthen existing sexual reproductive health services and include HIV testing, and linkages to care and treatment services, provide an opportunity to lay the foundations for wide-scale provision of microbicides. The potential to enhance health outcomes in women and infants and potentially affect rates of new HIV infection may soon be realised.
Introduction
Women feature more strongly in this decade of the HIV pandemic than the previous two. Young women in sub-Saharan Africa and in the USA are disproportionately affected by human immunodeficiency virus (HIV) compared with their male counterparts. More than one-half of all global HIV infections are in women infected primarily through sexual transmission.
Women’s vulnerability to HIV infection is a result of a complex interplay of social, cultural, biological, political and economic factors. Current HIV prevention options are mainly dependent on male partner co-operation. Power disparities between men and women limit the ability of women to negotiate safer sex practices, and this is particularly pronounced for young women under 20 years of age. In the absence of an effective vaccine, other approaches that reduce new HIV infections, even if moderately effective, are urgent.
To this end, investment in the development of microbicides has occurred over the past 17 years, and efforts are designed to enable women to control their HIV risk through a self-initiated method. The CAPRISA 004, 1% tenofovir gel trial provided the first evidence that such a technology was within our reach. This antiretroviral agent specifically formulated for topical application in the female genital tract has limited systemic toxicities. If effectiveness is confirmed in the FACTS 001 trial, tenofovir gel may fill an important HIV prevention gap for women in the next 3–5 years. Mathematical modelling data based on the CAPRISA 004 trial findings, indicates that, over 20 years, the use of tenofovir gel in South Africa alone could avert up to 2 million new infections and 1 million deaths from acquired immune deficiency syndrome (AIDS), which would significantly affect the epidemic in South Africa. Tenofovir gel use in more than 25% of sexual encounters could significantly alter the course of the epidemic in southern Africa, and thereby globally.
Further down the microbicide development pipeline, we anticipate additional products with greater efficacy through enhanced drug-delivery mechanisms such as vaginal rings, sustained-release formulations, synergistic drug combinations, and multi-purpose technologies that, for example, combine fertility control and HIV risk-reduction needs. Antiretroviral-based microbicides are now seen as the future of HIV control.
It is at this critically important stage, and before product licensure, that we ask the difficult implementation questions. These include determining the potential barriers to access and uptake, and how to best incorporate this prevention strategy into existing healthcare delivery systems to maximise access to women in resource-limited settings who can benefit most from such technologies expeditiously.
Do microbicides meet the criteria for an effective intervention?
Resources for meeting healthcare needs in low-income countries are limited. Introduction of new technologies and innovations have to be cognisant of this, and careful attention needs to be paid to criteria used to determine public health benefits of new interventions for optimal, efficient and effective use of limited resources.
Given the recent advances in evidence-based HIV prevention approaches to reduce sexual transmission of HIV and the diversity of HIV epidemics geographically, populations at risk, levels of efficacy and healthcare delivery infrastructure, Shelton proposed a useful framework comprising 20 criteria to guide decision-making on use of scarce health resources in developing countries. We have adapted this guide to assess if microbicides have the potential to meet the criteria for an effective intervention. The criteria used are presented in Table 1 .
| Criterion | Comment |
|---|---|
| Health burden in low-income countries | High HIV burden; HIV prevention is a health priority; women younger than 24years have three- to six-fold higher rates of HIV infection compared with men. |
| Individual efficacy | First trial with tenofovir gel shows 39% effectiveness, but could be as high 54% with higher adherence. Most trials aim for at least 50% higher efficacy than placebo. |
| Scalability | Will benefit individual and reach scale by reducing transmissions within sexual networks. |
| Low cost | Cost issues will exist at initial production but likely to be reduced over time. |
| Simplicity | Fairly simple to administer but requires training at initiation and HIV and pregnancy requires on-going monitoring. |
| Safety | Safe with low systemic absorption; anticipate a good risk – benefit profile. |
| User acceptability | Microbicides have high user acceptability in trial settings; unable to date to test in real-world settings. |
| Family acceptability | Can be used without partner knowledge; some data available to support family acceptability. |
| Social norms | Limited community level data available that support microbicides. Advocacy efforts need to be strengthened. |
| Provider/medical culture | Motivation to avert HIV infection is high in countries burdened with disease. |
| Potential for integration | Excellent potential for integration into existing services, particularly sexual reproductive health and pre- and post-natal services. |
| Alternative approaches | Limited prevention options exist for women; none that are women-initiated and controlled. |
| Regulatory and policy requirements | Regulators such as the US Food and Drug Administration have agreed to fast-track microbicide candidates for registration; need sufficient efficacy and safety data for licensure; at least one other confirmatory trial; FACTS 001 is under way to confirm CAPRISA 004. |
| Procurement and logistics | Many low-income countries gaining experience with antiretroviral treatment and preventing mother-to-child transmission scale-up; systems are in place to address this; the South African government holds royalty-free license and is already exploring manufacturing options, market stratification and access across Africa. |
| Timing dependency | Only coitally administrated use has been tested to date; in the future we are likely to have multiple formulations and delivery vehicles, including vaginal rings and multi-purpose technologies. |
| Durability | Low durability; will need to be provided repeatedly; frequency could vary in the future based on formulation and delivery vehicle. |
| Behaviour dependency | A challenge; needs to be incorporated into current behaviour; new method that will need intense support initially and less with time. |
| Commercial sector compatibility | Potential for socially responsible private–public partnerships; already in place in South Africa. |
| Collateral benefits | Reduce maternal morbidity and mortality; avert infants infections, other sexually transmitted infection and enhance sexual and reproductive health services; women empowerment. |
| Sustainability | Requires ongoing commitment and investment. |
Do microbicides meet the criteria for an effective intervention?
Resources for meeting healthcare needs in low-income countries are limited. Introduction of new technologies and innovations have to be cognisant of this, and careful attention needs to be paid to criteria used to determine public health benefits of new interventions for optimal, efficient and effective use of limited resources.
Given the recent advances in evidence-based HIV prevention approaches to reduce sexual transmission of HIV and the diversity of HIV epidemics geographically, populations at risk, levels of efficacy and healthcare delivery infrastructure, Shelton proposed a useful framework comprising 20 criteria to guide decision-making on use of scarce health resources in developing countries. We have adapted this guide to assess if microbicides have the potential to meet the criteria for an effective intervention. The criteria used are presented in Table 1 .
| Criterion | Comment |
|---|---|
| Health burden in low-income countries | High HIV burden; HIV prevention is a health priority; women younger than 24years have three- to six-fold higher rates of HIV infection compared with men. |
| Individual efficacy | First trial with tenofovir gel shows 39% effectiveness, but could be as high 54% with higher adherence. Most trials aim for at least 50% higher efficacy than placebo. |
| Scalability | Will benefit individual and reach scale by reducing transmissions within sexual networks. |
| Low cost | Cost issues will exist at initial production but likely to be reduced over time. |
| Simplicity | Fairly simple to administer but requires training at initiation and HIV and pregnancy requires on-going monitoring. |
| Safety | Safe with low systemic absorption; anticipate a good risk – benefit profile. |
| User acceptability | Microbicides have high user acceptability in trial settings; unable to date to test in real-world settings. |
| Family acceptability | Can be used without partner knowledge; some data available to support family acceptability. |
| Social norms | Limited community level data available that support microbicides. Advocacy efforts need to be strengthened. |
| Provider/medical culture | Motivation to avert HIV infection is high in countries burdened with disease. |
| Potential for integration | Excellent potential for integration into existing services, particularly sexual reproductive health and pre- and post-natal services. |
| Alternative approaches | Limited prevention options exist for women; none that are women-initiated and controlled. |
| Regulatory and policy requirements | Regulators such as the US Food and Drug Administration have agreed to fast-track microbicide candidates for registration; need sufficient efficacy and safety data for licensure; at least one other confirmatory trial; FACTS 001 is under way to confirm CAPRISA 004. |
| Procurement and logistics | Many low-income countries gaining experience with antiretroviral treatment and preventing mother-to-child transmission scale-up; systems are in place to address this; the South African government holds royalty-free license and is already exploring manufacturing options, market stratification and access across Africa. |
| Timing dependency | Only coitally administrated use has been tested to date; in the future we are likely to have multiple formulations and delivery vehicles, including vaginal rings and multi-purpose technologies. |
| Durability | Low durability; will need to be provided repeatedly; frequency could vary in the future based on formulation and delivery vehicle. |
| Behaviour dependency | A challenge; needs to be incorporated into current behaviour; new method that will need intense support initially and less with time. |
| Commercial sector compatibility | Potential for socially responsible private–public partnerships; already in place in South Africa. |
| Collateral benefits | Reduce maternal morbidity and mortality; avert infants infections, other sexually transmitted infection and enhance sexual and reproductive health services; women empowerment. |
| Sustainability | Requires ongoing commitment and investment. |
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