Infectious Disease Alert Updates
By Carol A. Kemper, MD, FACP
Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center
How Much Should Injectable Cabotegravir for PrEP Cost?
SOURCE: Neilan AM, Landovitz RJ, Le M, et al. Cost-effectiveness of long-acting injectable HIV preexposure prophylaxis in the United States. Ann Intern Med 2022;175:479-489.
It’s an interesting question — how much should a drug cost or, more to the point, how much is society willing to pay for a drug? In this case, what value does society attach to the use of injectable cabotegravir (CAB-LA), a long-acting injectable integrase inhibitor, for the prevention of human immunodeficiency virus (HIV) infection? I always thought it was of interest that the original varicella vaccine ultimately was approved for use in children because it saved women from having to leave their jobs for childcare — a society economic argument — not a purely medical decision.
CAB-LA has proven to be effective in reducing the risk of HIV infection when used for pre-exposure prophylaxis (PrEP), and it received U.S. Food and Drug Administration approval for this purpose in December 2021. Yet, insurance companies are balking at the cost, and its availability has been limited. In a recent HIV prevention trial (HTPN 083), CAB-LA was compared with daily tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for PrEP in a large group of men and transgender women who have sex with men.1
Once the three-year study was unblinded, a 66% reduction in HIV incidence was observed in the CAB-LA arm vs. the TDF-FTC arm. However, delays in the recognition of HIV infection were observed in the CAB-LA arm, raising concerns about the risk of emerging drug resistance to the long-acting injectable. In contrast, while daily TDF-FTC is associated with a greater risk of non-compliance, and the resulting suboptimal drug concentrations lead to breakthrough infections, they seldom lead to drug-resistant infection.
Projecting over a 10-year period, the authors compared the cost benefits of CAB-LA with TDF-FTC, as well as branded tenofovir alafenamide fumarate-emtricitabine (TAF-FTC), in terms of overall effectiveness at preventing HIV infection, compliance with the regimen, retention with treatment, cost, and the risk of adverse long-term bone and renal side effects on TDF-FTC. Annual drug costs for generic TDF-FTC were estimated at $360, compared with $16,800 for branded TAF-FTC. To estimate the maximal benefit of CAB-LA, only those individuals at very high risk for HIV infection were included in the calculations (estimated at 5.32 infections per 100 person years), and that no resistance occurred while receiving the long-acting agent. In this very high-risk group, the incidence of HIV infection during CAB-LA vs. standard treatment was estimated at 0.26 vs. 1.33 per 100 person years, respectively.
In this very high-risk group (estimated at ~500,000 people in the United States), the number of primary HIV infections over a 10-year period was highest for no PrEP (n = 178,000), lower for generic TDF-FTC and branded TAF-FTC (n = 122,000), and lowest for CAB-LA (107,000). The cost for no PrEP was estimated at $33.5 billion vs. $30.7 billion for the two tenofovir regimens, representing a modest overall cost-savings for the tenofovir regimens. Compared with the cost of the tenofovir regimens, and assuming a threshold of $50,000 to $300,000 per Quality Adjusted Life Year (QALY), the maximum cost of CAB-LA would range from $3,000 to $6,600. If the minimal price for generic TDF-FTC was $360 per year, then the resulting maximum price premium for CAB-LA would be $1,900 (or $2,260 per year). If the effectiveness of CAB-LA were further improved, then the maximal price premium would increase to $4,000 per year (or $4,360 per year).
On the other hand, should the cost for branded TAF-FTC be $16,800 per year, and increase the willingness-to-pay threshold per QALY to $300,000, then the maximum price premium of CAB-LA over TAF-FTC would be $5,200 (total cost $22,000 per year). If the risk of HIV infection is lowered from very high risk to just high risk, then the calculated maximal price premium for CAB-LA compared with generic TDF-FTC would be less, at $2,100 (or $2,460 per year).
Although CAB-LA offers a modest benefit in the reduction of HIV in persons at risk and offers superior compliance, its high cost is difficult to justify, even in those at the highest risk for HIV infection. The superior effectiveness of the injectable agent is entirely due to its long-acting nature, obviating the need for a daily pill. If only compliance with the oral PrEP regimens were to improve, the modest gains of the injectable agent likely would be canceled.
- Marzinke MA, Grinsztejn B, Fogel JM, et al. Characterization of human immunodeficiency virus (HIV) infection in cisgender men and transgender women who have sex with men receiving injectable cabotegravir for HIV prevention: HPTN 083. J Infect Dis 2021;224:1581-1592.
Asymptomatic COVID Infection in Healthcare Workers
SOURCE: North CM, Barczak A, Goldstein RG, et al. Determining the incidence of asymptomatic SARS-CoV-2 among early recipients of COVID-19 vaccines (DISCOVER-COVID-19): A prospective cohort study of healthcare workers before, during and after vaccination. Clin Infect Dis 2022;74:1275-1278.
During the vaccine roll-out at the Mass General Brigham Hospital in Boston from December 2020 to April 2021, a subset of employees participated in a weekly assessment of COVID infection before, during, and for up to eight weeks following vaccination. A total of 2,247 employees were given weekly home kits for nasal swabs and an online survey of symptoms. Anyone testing positive was isolated for 14 days, and the research team came to their home every other day for nasal swabs for SARS-CoV-2 polymerase chain reaction (PCR), viral culture, and viral sequencing. The median age of the group was 37 years, the majority were female (78%), and nearly half (47%) provided direct medical care for patients with COVID infection. By the end of the study period, > 99% were fully vaccinated; the majority received the Moderna vaccine (64%) vs. Pfizer (36%). A total of 13,359 swabs were collected.
Nineteen employees tested positive for SARS-CoV-2 PCR (0.8%). Six of these occurred in the pre-vaccination period, 10 during the vaccination period, and three were fully vaccinated. Of these, 5/6 pre-vaccine infections were symptomatic, 6/10 in the intermediate period were symptomatic, and 1/3 fully vaccinated persons was symptomatic.
Cycle thresholds were available for 17 of 19 positive tests (89%), and generally were lower (i.e., higher viral loads) in those with symptomatic vs. asymptomatic infection. Seven participants, who were either partly or fully vaccinated, had fully analyzable data after the virologic substudy began, including three with symptomatic infection and four with asymptomatic infection. Detectable virus by PCR was observed out to day 10 and to day 11 in two of the symptomatic participants, who had culturable virus out to day 4 and to day 7. Both had B.1.17/Alpha variant. The third participant with symptomatic infection had an undetectable viral load and a negative culture within two days of their positive test. All four with asymptomatic infection had undetectable viral loads by day 2 following their positive test, and none had culturable virus.
This suggests that vaccinated healthcare workers with asymptomatic COVID-19 infection shed little to no virus and only for a short duration (≤ 2 days at most). The higher cycle thresholds and the inability to culture virus from these individuals indicate these transient low-grade infections may not represent contagious infection. On the other hand, some of these positive results could have been falsely positive.
A limitation to this study might be that asymptomatic infections were only detected at weekly intervals with the weekly surveillance home kits and may not fairly represent the onset of those infections. Weekly surveillance also could have underestimated the incidence of asymptomatic infection in this group of healthcare workers.
How Much Should Injectable Cabotegravir for PrEP Cost? Asymptomatic COVID Infection in Healthcare Workers
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