What is the use of anti-HIV injections when those who need it most can’t get it?
A new HIV prevention medicine could work even better than daily pills, but if nothing changes it costs more than R300,000 to treat one person for a year.
Who needs a pill or an injection that can prevent them from contracting HIV through sex the most? Those countries and parts of society with the most new HIV infections, because new infections among HIV-negative people are what such biomedical interventions (treatments and devices that make it harder for the virus to be transmitted) try to stop.
In the case of HIV, countries in sub-Saharan Africa have the highest HIV infection rates, particularly among African teenage girls and young women. And around the world, female sex workers and men who have sex with men contract HIV at considerably higher rates than non-sex workers and heterosexual men.
So when studies showed that an injection called CAB-LA (long-acting cabotegravir) – which you have once every two months – worked so well that it virtually wiped out the risk of getting infected with HIV through sex, doctors, researchers and activists were ecstatic.
But their excitement soon subsided when it emerged that the company that makes the injection, ViiV Healthcare, sells it for R54,000 a pop in the US (the country’s medicines regulator approved CAB-LA in December), which amounts to R323,700 per person per year.
Even in a high-income country such as the US, modelling studies have shown that the potential public health benefit of CAB-LA is jeopardised by its cost and that prices don’t reflect this preventive treatment’s true value.
So what now?
Those dependent on the public healthcare sector in South Africa (about eight out of 10 people) will not be able to access the CAB-LA injection at all at the price it is sold for in the US. ViiV Healthcare, however, clearly has an intention to make CAB-LA available in South Africa: the South African Health Products Regulatory Authority confirmed to Bhekisisa that the manufacturer applied for registration of the injection in December.
The obvious solution would be for ViiV Healthcare to issue voluntary licences to generic manufacturers who can produce the injection at about R38 a shot, according to projections by the Clinton Health Access Initiative (Chai), which is 1,000 times less than what the manufacturer is selling it at.
Generic drugs work the same way as their brand-name counterparts because they have the same active ingredient (the stuff that makes it work).
Even with a mark-up and the costs of administration (at the moment, the injection needs to be given by a trained health professional) a generic version would be only slightly more expensive than the HIV prevention pill we currently use in South Africa.
But in early March, ViiV Healthcare announced it will, in fact, not issue any voluntary licences – at least not for now. It is unclear why it made this decision, as the press release was vague on the reasoning, when the company has a long history of issuing similar licences. Equally frustrating, Viiv has not announced the price for its drug outside richer countries, nor the quantities available for distribution.
This is worrying, because it echoes a pattern from 20 years ago with antiretrovirals for treatment – drug companies would not issue licences, claiming the drugs were too difficult to make, that generics were unreliable, or they were not willing to lower their prices. Viiv Healthcare’s attitude is already causing concern, since it is restricting supply for implementation research projects, suggesting it cannot make enough of its product.
To make things worse, CAB-LA was tested on South Africans, but the country may find itself without this form of HIV prevention.
In the absence of a plausible explanation, it seems that profit-before-people, as we’ve seen throughout the Covid-19 pandemic with vaccine manufacturers, could be behind ViiV Healthcare’s decision, leaving an urgent question: Is there any meaningful use for a health intervention if those who need it most can’t access it?
What is CAB-LA and how does it work?
The CAB-LA injection is a type of pre-exposure prophylaxis (PrEP) – medicine you can take to reduce your chances of getting infected with a germ.
If you take PrEP to protect yourself against HIV infection, then that medicine, whether it’s a pill or injection, has to be taken before you get exposed to it, so that there’s enough of the drug in your body to shield the immune system from infection.
The ingredient in CAB-LA that makes it work is called cabotegravir, an antiretroviral (ARV) drug (medicine used to treat people with HIV). ARVs don’t cure people from HIV, but help to keep the infection under control by preventing the virus from making copies of itself and infecting millions of cells in your body.
But studies have shown that HIV-negative people can also use ARVs to protect themselves from getting infected. So if you have enough of an ARV such as cabotegravir in your body, it can prevent the virus from getting a foothold. This is like taking a drug to stop malaria, or contraception to stop getting pregnant.
This doesn’t mean that PrEP works 100% all the time, but in the case of CAB-LA, the HPTN 084 trial has shown that it is 89% more effective than the daily PrEP pill at lowering the chances of getting infected with HIV.
Is CAB-LA the only type of PrEP for HIV?
Around the world, the most common type of PrEP for HIV is a daily pill called Truvada (or generic versions of it), which contains two types of ARVs, tenofovir and emtricitabine, and is widely available in South Africa, in state clinics and in the private sector.
There are also forms of PrEP such as vaginal rings, but they’re less effective than pills.
With close to 7.6 million South Africans estimated by the Thembisa model to be HIV positive and about 200,000 new HIV infections per year, the country desperately needs PrEP to help slow down new infections.
The Health Department started to roll out oral PrEP (pills) in 2016. Department figures show that between June 2016 and December 2021, 450,606 people, especially sex workers, transgender people, those who inject drugs, and teenage girls and young women, have accessed PrEP though government clinics and hospitals.
It costs the department about R60 for one patient’s monthly supply of oral PrEP – when administration costs such as blood tests and nurses’ salaries are included, it comes to about R90. This is cost effective, because to treat a person who gets infected with HIV with ARVs in the government sector comes to about R300 (five times the price of preventing them from getting infected). A costing preprint study (not yet peer reviewed) found that to be cost effective CAB-LA cannot cost more than twice the current cost of oral PrEP.
The challenge with oral PrEP, however, is that people need to remember to take it each day, because there’s a direct correlation between how well the pills work and how often they’re taken. So when people forget to take their pills consistently, the tablets provide less protection.
Studies show that when oral PrEP is taken daily, it can give someone protection from HIV infection between 92% and 98%. But research also shows that teen girls and young women particularly often struggle with sticking to a daily regimen.
Because CAB-LA doesn’t have to be taken daily but only once every two months, it may be easier to keep it up, which is, at least partly, why it works better than oral PrEP. And it’s not just with PrEP that long-acting injections often work better than pills; the same trend has been seen with long-acting contraception and injectable psychiatric treatment.
However, for CAB-LA to be cost effective for South Africa, researchers say the Health Department would need to be able to procure it at the same price as oral PrEP.
For the two-monthly injection that would come to R120 a shot. If generic manufacturers could produce treatment for about R300 a year (R38 a shot), as Chai research indicates, CAB-LA would be almost 10 times cheaper than oral PrEP.
But if ViiV Healthcare holds on to its patent and continues to refuse to share its recipe and know-how and not issue voluntary licences to generic companies, it is unlikely that the state sector will be able to afford it, even at a fraction of the US price. It will be too expensive for many people in the private health sector too.
Why does ViiV Healthcare not want to issue generic licences?
ViiV’s unwillingness to work with generic manufacturers was unexpected, especially since the company has a good track record of making ARVs available to poorer countries at reasonable prices.
One example is the partnership between ViiV, international donors and generic manufacturers, which resulted in the children’s version of the antiretroviral drug dolutegravir being available for less than R600 a year instead of R6,000 for the brand-name version.
The World Health Organization recommends dolutegravir as one of its go-to drugs to treat HIV and recently extended the guideline to include children because it is effective, easy to take and there’s little chance that the virus will become resistant to it.
In a statement in early March, ViiV Healthcare claimed that finding a suitable generic partner “will be challenging, due to the complexities of manufacturing, regulatory requirements, capital investment needs and unpredictable demand”, and as such it would be “the sole supplier of cabotegravir LA for PrEP globally, including in resource-limited settings, at least during the initial years of introduction of the medicine”.
If CAB-LA remains priced as it is now, and without the option for a generic alternative, poorer countries will be last in line to benefit from new treatment options. Without urgent efforts to change this, getting a generic version of CAB-LA to Africa “could be delayed by nearly a decade, if not longer”, says Afrocab, a network of HIV treatment advocates on the continent.
Why is ViiV Healthcare refusing to help?
The manufacturer’s attitude is reminiscent of the inequities and delayed access to Covid-19 tests, treatments and vaccines. Despite the international procurement mechanism, Covax, and other initiatives that were set up to help poorer countries access jabs, richer countries were consistently first in line for vaccine orders from manufacturers. This played a big part in only about 15% of people in Africa having been fully vaccinated – compared with 72% in the UK, 91% in Singapore and 82% in Canada.
This is despite research showing that people in low-income countries were more willing to be vaccinated than people in rich countries.
A similar trend of inequitable access was seen with Covid testing, with less than 1% of the more than 3.2-billion tests globally performed in countries with small public health budgets.
The Covid pandemic, like the HIV epidemic, has shown us that despite the rhetoric around the need for universal health coverage and equity, the poor are bound to get the short end of the stick – even when they are the most vulnerable, because what we have witnessed is that for pharmaceutical companies, profits are more important than the health of people.
The non-transparent and excessive pricing of pharmaceutical products has been a long-standing concern – some have gone as far as calling the pharma companies’ profiteering from the Covid-19 crisis a crime against humanity.
Analyses suggest that prices of pharmaceutical products are generally unfairly high – even when considering manufacturers’ claims that they need to recoup investment in research and development and to show their shareholders high returns on their investments. What seems to be forgotten is that a significant part of pharmaceutical research – especially for Covid – is funded by public investment.
To improve access to affordable medicines we have to change the way drug companies operate. United Nations recommendations encourage governments to be more flexible with intellectual property rights for health products – international trade experts agreed to this in 2001. Governments should also invest more in the research and development of medicines and the private sector should be more transparent about its operations to increase equitable access.
But these have largely not been implemented. The Access to Medicine Index ranks 20 of the largest pharmaceutical companies annually on their programmes to improve access to medication. The 2021 edition found that only eight companies implemented ways to make it easier to get medicine. In poorer countries, fewer than half of the most-needed medicines were available.
Public health advocates have long argued that life-saving pharmaceutical products should be regarded as “public goods” and that pricing decisions should be more transparent and fair. This has to involve changing patent protection rules and also encouraging local licensing and manufacturing – with government backing. It will go a long way to realising affordable healthcare for all. DM/MC
Professor Yogan Pillay is extraordinary professor at the global health department at Stellenbosch University and the country director of the Clinton Health Access Initiative. Professor Francois Venter is the head of the health policy and research organisation, Ezintsha at Wits University. Fatima Hassan is the founding director of the Health Justice Initiative.