South Africa is expected to begin piloting the every-other-month HIV prevention shot early next year, according to the international medicine financing initiative Unitaid, with new modelling released last week showing that the injection could prevent as many as 52 000 new HIV infections in the next two decades if rolled out nationally.
But to be cost-effective in South Africa, the research suggests the price of the injection must fall to levels that drugmaker ViiV Healthcare says are unrealistic, writes Laura Lopez Gonzalez in Spotlight.
Wits Reproductive Health and HIV Institute (Wits RHI) and the national Health Department are expected to begin providing injections of the antiretroviral cabotegravir to young women to prevent HIV infection as part of a small Unitaid-funded project, spokesperson Hervé Verhoosel said.
Given every other month, the injection is the latest form of pre-exposure prophylaxis (PrEP) to use antiretroviral medication to prevent HIV infection in HIV-negative people.
Oral PrEP in the form of a once-a-day tablet has been available in South Africa since 2016. Today, the pill is available at more than 2 000 sites nationwide. Known by its brand name Truvada, the tablet combines two antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate. When taken correctly, it can reduce the risk of contracting HIV by almost 99%.
Still, results from two large clinical trials led in part by South African researchers have found that people injected with the antiretroviral cabotegravir every other month were about 80% less likely to contract HIV than those on the HIV prevention pill. The bi-monthly shot probably outperformed Truvada, the World Health Organisation said, mainly because it was easier for people to get an injection every two months than to take daily pills.
The Wits RHI pilot will follow the jab’s approval by the South African Health Products Regulatory Authority (Sahpra). Unitaid said it expected Sahpra to approve the injection early next year. ViiV Healthcare applied for regulatory approval with Sahpra in August 2021. The United States Food and Drug Administration approved it in December 2021.
The Wits RHI pilot, which will see the injection provided in some public health facilities and also via the organisation’s mobile clinics, is expected to be the first of several planned demonstration projects to see how best to roll it out.
Similar programmes are slated for Clicks pharmacies, for instance, according to the HIV prevention organisation AVAC. Divisional director of the health research organisation Ezintsha Dr Francois Venter said they would be partnering with Clicks and the Health Department to offer the injection alongside Truvada and a monthly vaginal ring that uses the antiretroviral dapivirine to prevent HIV infection.
In large clinical trials, the soft silicon ring reduced women’s risk of contracting HIV by between 27% and 35%, but this increased to 50% or more in more real-world settings, the WHO said.
The catch may be the cost: shot retails for hundreds of thousands of rands in US
In the short term, the HIV prevention jab is likely to be confined to small pilot projects as the Health Department – like many worldwide – continues to study how best to bring complicated injections out of health facilities and closer to communities.
Price is also a potential stumbling block. The injection can cost up to R391 000 per patient annually in the US. But for it to be cost-effective in South Africa, this price would have to fall to at least R1 800 – less than 1% of the official US price tag, according to new modelling published in The Lancet HIV by the University of the Witwatersrand’s Health Economics and Epidemiology Research Office (HE2RO).
ViiV Healthcare, however, said the price was unrealistic.
“Based on ViiV’s experience making (long-acting cabotegravir) for PrEP, this significantly underestimates the cost of manufacture,” ViiV Healthcare spokesperson Catherine Hartley said in September in response to a pre-print of the HE2RO study.
“Long-acting cabotegravir is a highly innovative, complex, sterile injectable medicine,” Hartley explained. “Manufacturing is more expensive and much harder than for generic oral PrEP, which is a simple white tablet.”
HE2RO’s study sought to compare the cost-effectiveness and impact of the HIV prevention shot with Truvada to determine the price tag at which the injection would become cost-effective.
The model also makes several assumptions, for instance, how fast a rollout of the vaccine would grow and that more people would opt for the HIV prevention shot over the pill – an assumption borne out by available data.
Partly because more people are likely to choose the injection over a pill, and because it’s easier to take, HE2RO found that a national roll-out of the shot would avert three times as many infections and save triple the number of lives as increasing access to oral PrEP alone.
But for the injection to be cost-effective, the study found, it could only cost the same or double what South Africa currently pays for oral PrEP.
“Although long-acting injectable cabotegravir has the potential to change HIV prevention, for large-scale implementation across low-income and middle-income countries, it first needs to be affordable,” researchers write. “Lessons learned from oral PrEP programmes show that scale-up and demand creation should be coordinated between all partners and should be fast enough to build momentum and yield results as high as [we have] projected.”
In July, ViiV Healthcare announced it had entered into an agreement with the Medicines Patent Pool (MPP) to grant an initial three licences to generic manufacturers with hopes of producing affordable versions of the shot for low- and lower-middle income countries – as well as all sub-Saharan African countries regardless of income level. The deal includes South Africa.
But, the MPP predicts it will take between three and five years before generics are ready to be marketed.
Until that happens, ViiV Healthcare publicly committed at this year’s International Aids Conference to providing affordable prices for countries covered by the MPP deal. In The Lancet HIV, researchers write that ViiV is considering what it says is a non-profit price of between R4 262 and R4 794 per patient per year.
ViiV Healthcare declined to confirm any pricing figures. Instead, the company said it was working with AVAC, Unitaid, the Bill & Melinda Gates Foundation, and others to examine affordable pricing and innovative financing.
“Given that work is getting started and we don’t want to pre-empt it, we’re not in a position to talk about pricing details or comment on specific numbers,” Hartley said. “We’re committed to engaging, collaborating positively, and working openly with global health partners and the HIV community to reduce the cost of long-acting cabotegravir for PrEP to help enable broad access for people who could benefit from it.”
Study details
Relative cost-effectiveness of long-acting injectable cabotegravir versus oral pre-exposure prophylaxis in South Africa based on the HPTN 083 and HPTN 084 trials: a modelled economic evaluation and threshold analysis
Lise Jamieson, Leigh Johnson, Brooke Nichols, Sinead Delany-Moretlwe,
Mina Hosseinipour, Colin Russell et al.
Published in The Lancet HIV on 7 November 2022
Summary
Background
Long-acting injectable cabotegravir, a drug taken every 2 months, has been shown to be more effective at preventing HIV infection than daily oral tenofovir disoproxil fumarate and emtricitabine, but its cost-effectiveness in a high-prevalence setting is not known. We aimed to estimate the incremental cost-effectiveness of long-acting injectable cabotegravir compared with tenofovir disoproxil fumarate and emtricitabine in South Africa, using methods standard to government planning, and to determine the threshold price at which long-acting injectable cabotegravir is as cost-effective as tenofovir disoproxil fumarate and emtricitabine.
Methods
In this modelled economic evaluation and threshold analysis, we updated a deterministic model of the South African HIV epidemic with data from the HPTN 083 and HPTN 084 trials to evaluate the effect of tenofovir disoproxil fumarate and emtricitabine and long-acting injectable cabotegravir provision to heterosexual adolescents and young women and men aged 15–24 years, female sex workers, and men who have sex with men. We estimated the average intervention cost, in 2021 US$, using ingredients-based costing, and modelled the cost-effectiveness of two coverage scenarios (medium or high, assuming higher uptake of long-acting injectable cabotegravir than tenofovir disoproxil fumarate and emtricitabine throughout) and, for long-acting injectable cabotegravir, two duration subscenarios (minimum: same pre-exposure prophylaxis duration as for tenofovir disoproxil fumarate and emtricitabine; maximum: longer duration than tenofovir disoproxil fumarate and emtricitabine) over 2022–41.
Findings
Across long-acting injectable cabotegravir scenarios, 15–28% more new HIV infections were averted compared with the baseline scenario (current tenofovir disoproxil fumarate and emtricitabine roll-out). In scenarios with increased coverage with oral tenofovir disoproxil fumarate and emtricitabine, 4–8% more new HIV infections were averted compared with the baseline scenario. If long-acting injectable cabotegravir drug costs were equal to those of tenofovir disoproxil fumarate and emtricitabine for the same 2-month period, the incremental cost of long-acting injectable cabotegravir to the HIV programme was higher than that of tenofovir disoproxil fumarate and emtricitabine (5–10% vs 2–4%) due to higher assumed uptake of long-acting injectable cabotegravir. The cost per infection averted was $6053–6610 (tenofovir disoproxil fumarate and emtricitabine) and $4471–6785 (long-acting injectable cabotegravir). The cost per long-acting cabotegravir injection needed to be less than twice that of a 2-month supply of tenofovir disoproxil fumarate and emtricitabine to remain as cost-effective, with threshold prices ranging between $9·03 per injection (high coverage; maximum duration) and $14·47 per injection (medium coverage; minimum duration).
Interpretation
Long-acting injectable cabotegravir could potentially substantially change HIV prevention. However, for its implementation to be financially feasible across low-income and middle-income countries with high HIV incidence, long-acting injectable cabotegravir must be reasonably priced.
See more from MedicalBrief archives:
Start planning cabotegravir injection rollout, say SA experts
FDA approves monthly injectable Cabenuva to treat HIV
Long-acting ARV given as two monthly injectable PrEP protects against HIV
Cost and uncertainty over uptake bedevil Africa’s uptake of injectable PrEp