The second in a three-part series looking back at the challenges and successes of HIV/AIDS treatments over the past 40 years and potential medical breakthroughs to come (read part one here) from Lenias Hwenda of Medicines for Africa. Here, Hwenda shines a light on the importance of preventing mother-to-child transmission – including the remarkable success of Botswana’s approach to this issue –, reducing women’s extreme vulnerability to HIV infection, long-term prevention with injectable pre-exposure prophalaxis, and curbing the current upward trajectory of HIV infections.


Preventing mother-to-child transmission (PMTCT)

In pregnant women, maternal infection is the primary driver of HIV transmission in children. Mother-to-child-transmission (MTCT) typically occurs either during pregnancy, childbirth, or through breastfeeding. Available evidence shows that HIV positive mothers who do not receive antiretroviral (ARV) treatment have a 15-45 percent probability of transmitting the virus to their babies during pregnancy, labour, delivery or breastfeeding. When both mother and baby receive treatment from the beginning of pregnancy to the end of breastfeeding, that risk drops to 5 percent. Sustained efforts to prevent mother-to-child transmission has led to a 52 percent decline in mother-to-child transmission. Even though fewer babies born to HIV mothers became infected with the virus in 2021, this is however not enough.

At a global level, widespread skepticism and naysayers dismissed Botswana’s approach as a naïve and neither feasible nor practical. Nevertheless, paying for the approach from the national budget, Botswana would demonstrate phenomenal success in scaling up access to ART to prevent mother-to-child transmission

Nevertheless, much of the progress we see today was once deemed implausible for economic reasons. It shows what is possible when there is political will and leadership and Botswana is an excellent example of that. The country used to have the worst adult HIV prevalence worldwide – almost 40 percent. Under President Festus Mogae’s leadership, Botswana took unprecedented action to become an early adopter of best practices to preventing HIV transmission that would later become global recommendations. It was the first country to roll out a test-all and treat-all free antiretrovirals to all citizens living with HIV. First, Botswana made routine testing of all pregnant women a mandatory national policy in 2005 before expanding it to neonates so that all newborns could be diagnosed early.

At a global level, widespread skepticism and naysayers dismissed Botswana’s approach as a naïve and neither feasible nor practical. Nevertheless, paying for the approach from the national budget, Botswana would demonstrate phenomenal success in scaling up access to ART to prevent mother-to-child transmission. Perinatal transmission dropped from 40 percent in 1999 to two percent in 2020. By 2013, all pregnant and breast-feeding Batswana women with HIV were routinely offered ARV treatment to reduce mother-to-child transmission. Integrating prevention of mother-to-child transmission into basic sexual and reproductive health services further increased uptake of test and treat during pregnancy from 49 percent in 2002 to 98 percent in 2010. Botswana would eventually extend the treat all strategy for limiting the spread of HIV within the population with equally good results. Today Botswana is one of 15 countries certified to have eliminated mother-to-child transmission. This is an enormous achievement given its outsized epidemic at the start. Botswana set global standards of care that are today the WHO guideline for best practice in HIV care.


Reducing women’s extreme vulnerability to HIV infection

In Africa, based on sheer numbers alone, the extreme vulnerability of young women at the prime of their reproductive and economic lives to HIV infection makes preventing mother-to-child-transmission arguably one of the most important interventions. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS), in 2021, women accounted for 63 percent of new infections on the African continent of which there were 1.5 million. In the same year, six of every seven new infections occurred in adolescent girls. Between the age of 15 and 24 women’s risk of living with HIV is double that of their male peers. Unlike in other regions, African women are disproportionately affected by HIV/AIDS than men with young women and adolescent being the worst affected. Women’s extreme vulnerability is rooted in societal norms and structures underpinned by gender inequality that drives women social, economic and political insecurity. Addressing this persistent and extreme vulnerability of women of reproductive age across the continent of Africa is essential to limiting high rates of transmission within the African region.

Addressing this challenge will take all of society. It requires the social and economic empowerment of women in a way that addresses the factors that increases women’s vulnerability and civic education to change societal attitudes towards women. Providing women-controlled methods of preventing infection such as vaginal microbicides is one way to reduce women’s vulnerability to infection. This may not be the ultimate solution. It is however one more tool that can help to protect women. I worked on an HIV microbicide in my early scientific career at the Rockefeller University in New York. It did not succeed. Since then scientists have successfully generated proof of concept that a self-inserted vaginal ring infused with a slow-release antiretroviral like dapivirine, a nonnucleoside reverse transcription inhibitor, provides protective efficacy and reduces HIV incidence with an efficacy rate of 31 percent. The WHO recommends that this ring should be offered to women at substantial risk of HIV infection as part of combination prevention approaches. Another additional approach to reducing HIV transmission to women is increasing voluntary male circumcision which help to reduce men’s ability to transmit the virus during sexual intercourse.


Long term prevention with injectable pre-exposure prophalaxis

One of the most significant developments in public-health interventions to prevent HIV infection during the past 15 years, is the discovery and use of pre-exposure prophylaxis (PrEP). PrEP is the use of antiretroviral medicines to prevent infection in people who are not infected. Coupled to the expanded provision of treatment as prevention, PrEP has helped to reduce the incidence of HIV worldwide. Its use is expanding globally. It is now entering a new phase in which the available options are expanding and becoming more diverse. The ability to provide different HIV prevention options is important because it expands individual choice. Greater individual choice translates to more effective prevention at population level. It allows people to have different preferences for a particular type of PrEP giving them the ability to choose that which best suit their needs.

If widely accessible, expanded access to long-acting PrEP has the potential to radically change the course of the HIV epidemic worldwide

The oldest available PrEP is an oral pill taken either daily or around sexual activity. It has been in use for over a decade. When taken consistently, oral PrEP can reduce the risk of HIV by almost 100 percent. Oral PrEP can however be inaccessible, expensive and stigmatizing for many people. The need to take it every day or before and after sexual activity makes it cumbersome for some. This is why the recent newly introduced long-acting injectable PrEP given every two months holds greater promise. Long-acting cabotegravir is almost 100 percent effective at preventing HIV. It helps to overcome previous barriers to oral PrEP. For instance, it is easier to manage than oral pills since the injections are taken every two months. This empowers individuals to adhere to their medication more easily thereby improving the effectiveness of PrEP as HIV prevention. Modelling studies showed that in the context of generalised HIV epidemics in Africa, long-acting cabotegravir as PrEP significantly reduced HIV incidence over a period of 20 years. This helped to reduce new infections.

If widely accessible, expanded access to long-acting PrEP has the potential to radically change the course of the HIV epidemic worldwide. Studies published in the Lancet estimate that there could be 2.4–5.3 million PrEP users by the end of 2023. A number of African countries like Zimbabwe and South Africa have already granted cabotegravir marketing approval for use as HIV pre-exposure prophylaxis. This means that every two months, eligible individuals can now receive this injection to prevent sexually-acquired HIV infection. It is likely however that individuals and communities will face barriers to accessing PrEP. The biggest limitation to the potential benefits of PrEP is likely to be the cost of accessing it, its availability and having health-care professionals who are knowledgeable enough about it to appropriately guide patients. Nurse-led PrEP consultations and prescription would help resource-limited settings overcome access barriers from lack of skilled personnel.

The great news is that the choice of PrEP is set to expand. A variety of new HIV PrEP options are in clinical trials including long-acting oral, injectable, implantable and infusion options that can be taken at different time intervals. Having diverse PrEP modalities will allow individuals to access the right PrEP option for their specific prevention needs as appropriate. Ultimately, what public health needs is the ability to deploy a combination of tools that include widespread HIV testing, early ART initiation, women-controlled prevention and PrEP for those at risk. More options capable of accommodating the various preferences of people in need of HIV prevention who may require different schedules helps to maximise the opportunity to significantly limit the spread of HIV. To optimise public health benefits, the fifth decade of HIV must put equitable access to modern prevention methods at the centre of HIV and public health programmes.


Curbing the upward trajectory of HIV infections

Whilst HIV continues to be a serious public health issue, the danger is that the decline in new HIV infections and deaths from the catastrophic levels at the turn of the century creates complacency that AIDS is almost over. The most effective public health intervention possible, a vaccine, remains elusive. The advances in biomedical interventions for HIV/AIDS control simply cannot achieve what a vaccine can. Women continue to be extremely vulnerable. The trajectory of new infections is upwards. Too many are still getting infected. In 2020, about 1.5 million people were newly infected by HIV. Persistent stigma and discrimination against those with HIV/AIDS are major factors. Within the healthcare setting, affected people continue to encounter blaming, judging and victimizing language that deter them from seeking care. This causes far too many to shy away from seeking testing, treatment and care which helps to limit onward transmission. Addressing major obstacles that affect people’s willingness to seek and accept testing in many parts of the world is essential for further progress.

In the absence of a vaccine, removing such obstacles will put the goal of eliminating HIV by 2030 within grasp. We cannot make further progress without reversing the trend of rising infections. This will take unwavering commitment towards supporting the most vulnerable and equipping them with relevant available prevention tools. For instance, measures like making diagnosis more easily available through self-testing at home could have a significant impact. Countries like Zimbabwe, Malawi, Zambia, Lesotho, South Africa and Eswatini already offer self-testing under the IAVI HIV Self Testing Africa (STAR) initiative. The consequence of failing to reverse the upward infection trends whilst more people with HIV are surviving longer, and the incidence and the population is growing is that the number of people living with HIV will continue to grow. For instance, 24 percent more people were living with HIV/AIDS in 2019 compared to 2010.

Testing and treating must remain a critical strategy for reducing the risk of untested individuals continuing to serve as reservoirs that seed the unrelenting transmission of the virus within communities. Giving individuals the means to discreetly seek treatment can effectively counter this by reducing the number of people with unsuppressed viremia who maintain high infection rates within communities and drive HIV incidence up. Within regions, countries and even specific vulnerable populations like men who have sex with men, unsuppressed viremia is a known driver of infections. There is a great need to incorporate behavioral and structural interventions that emphasise control strategies that address the social and economic determinants of HIV epidemic. Whilst biomedical prevention interventions remain important, the next decade of HIV/AIDS must make structural and behavioral interventions the cornerstones of prevention efforts. Public health should also prioritize research on integrated strategies for HIV prevention which has been immensely underprioritized.