HIV prophylaxis shows promise

Vulnerable groups

(In sub-Saharan Africa, teenage girls and young women are most at risk of HIV infection. There are 2,000 new infections in this group every week. These women are vulnerable because of the high prevalence of gender-based violence and the commonality of age-disparate relationships and transactional sex)

  

The rate at which people are being infected by HIV remains greater than that at which people are initiating treatment. This imbalance will stop the eradication of HIV/AIDS. The mismatch begs for increased investment in primary prevention.

Primary prevention caters for people who are HIV-negative. It aims to reduce their chance of becoming infected.

In certain populations, known as key populations, the burden of infection is disproportionately high. These include men who have sex with men, sex workers, people who inject drugs, transgender people, and, in sub-Saharan Africa, adolescent girls and young women.
Primary prevention should be tailored, and scaled up, for these groups.
Primary prevention can be provided in a number of ways, but the most exciting new innovation is pre-exposure prophylaxis (PrEP).

PrEP is the use of antiretrovirals by HIV-uninfected people to prevent HIV transmission. It is commonly given as a daily pill (sold as Truvada) to be taken orally in the same way that contraceptives are used to prevent pregnancy or antimalarial pills are taken before travelling to a high malaria-risk area.
Numerous clinical trials and demonstration projects in diverse settings and populations have been conducted with PrEP all showing that it works.
PrEP is easy to take. It is also largely side-effect free and safe.
There is one hitch: it has to be taken consistently at the time of HIV exposure. Adherence has been oral PrEP’s biggest stumbling block.

 

That is why a huge effort is being made to find alternative ways to take PrEP. New formulations in the pipeline include long-acting injections, monthly vaginal rings, implants and topical gels, films and dissolving topical pills.
The hope is that new formulations will make PrEP more accessible and convenient, particularly for adolescents and young people who may find a daily intervention cumbersome.
Adherence is key. To block HIV transmission PrEP must be "in the system" at the time of HIV exposure. Its effectiveness decreases rapidly when this "effective coverage" is inconsistent. Good adherence gives almost 100% HIV transmission prevention. Poor adherence results in little to no protection.
This is why, where possible, a daily dose during times of risk is recommended. But this may be difficult to achieve for some.
In PrEP trials the following reasons were given for poor adherence: fear/experience of side effects; fear of interactions with alcohol and other drugs; forgetfulness; dislike of pill-taking, and fear of the discrimination associated with taking an anti-HIV pill.
Alternative dosing strategies using longer-acting formulations and PrEP delivery methods may well be another way to increase PrEP effectiveness.
Topical gels, which can be applied before and after sex to rectal and vaginal tissue, were the first alternative formulations to be tested. But the results in women have been inconsistent.
This formulation still holds promise in men who have sex with men although efficacy trials have not yet been conducted.

 

 

An alternative strategy is a monthly vaginal ring, which in its current form contains slow-release dapivirine (an antiretroviral). Two large phase III clinical trials have demonstrated that the ring is effective and can reduce the chance of HIV infection by 27%-31%. In a sub-analysis of different ages, older women once again fared better than young women.
The benefit of the vaginal ring is that there are fewer side effects because the drug is released locally and only a small amount enters the blood stream. The other huge advantage is that women are encouraged to insert and forget it, only changing the ring monthly. The limitation is that it is only suitable for women and vaginal intercourse.
The vaginal ring is undergoing further investigation.
Another tool that is being investigated and could overcome the need for a daily pill is a long-acting monthly injection. An injection of the antiretroviral cabotegravir (cabotegravir LA) has been shown to be very effective at lowering viral loads in people being treated for HIV when administered every two months. Also being investigated are dissolving vaginal films — a bit like breath fresheners — as well as quick-dissolving pills.
Perhaps most exciting of all is the prospect of an implant, a small rod that can be surgically placed just under the skin and will slowly release antiviral protection over months.
New formulations are being investigated that will combine treatment for contraception and preventing sexually transmitted infections. It is hoped that these multifunctional preventions may further encourage people to use these products consistently.

 

 

A new challenge to the field is how these new clinical trials can be efficiently designed. To qualify for first-line use of PrEP, new pills and products will need to have improved or equivalent efficacy compared to the current oral PrEP. And they would need to have reduced or equivalent side effects.
All these formulations and delivery methods are still in the early stages of testing, but look to be out on the market within the next two to five years depending on their success.
In sub-Saharan Africa, teenage girls and young women are most at risk of HIV infection. There are 2,000 new infections in this group every week. These women are vulnerable because of the high prevalence of gender-based violence and the commonality of age-disparate relationships and transactional sex. These conditions can make it difficult for women to negotiate safer sex practices.
PrEP would enable these women to protect themselves in advance, without their partner’s knowledge or consent.
Kenya and SA are the only African countries that have granted regulatory approval for PrEP. Neither have started to roll it out.
New interventions can only be useful if deployed and scaled up to the populations most in need. This raises questions of cost versus impact. It is hoped new formulations and delivery systems will enhance choice, encourage use, and provide a platform from which PrEP distribution can be advocated.

• First published in The Conversation. Bekker is professor of medicine and deputy director of the Desmond Tutu HIV Centre at the Institute of Infectious Disease and Molecular Medicine, University of Cape Town