HTLV-1 Transmission and HIV Pre-exposure Prophylaxis: A Scoping Review

Abstract

HIV pre-exposure prophylaxis (HIV-PrEP) is effective in reducing the likelihood of HIV acquisition in HIV-negative people at high risk of exposure. Guidelines recommend testing for sexually transmitted infections (STIs) before starting, and periodically on PrEP, including bacterial infections, HIV, hepatitis C virus, and, for those who are non-immune, hepatitis B virus. Diagnosed infections can be promptly treated to reduce onward transmission. HTLV-1 is not mentioned; however, it is predominantly sexually transmitted, causes adult T-cell leukaemia/lymphoma (ATL) or myelopathy in 10% of those infected, and is associated with an increased risk of death in those without any classically HTLV-associated condition. The 2021 WHO Technical Report on HTLV-1 called for the strengthening of global public health measures against its spread. In this scoping review, we, therefore, (1) discuss the epidemiological context of HIV-PrEP and HTLV-1 transmission; (2) present current knowledge of antiretrovirals in relation to HTLV-1 transmission prevention, including nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and integrase strand transfer inhibitors (INSTIs); and (3) identify knowledge gaps where data are urgently required to inform global public health measures to protect HIV-PrEP users from HTLV-1 acquisition. We suggest that systematic seroprevalence studies among PrEP-using groups, including men who have sex with men (MSM), people who inject drugs (PWIDs), and female sex workers (FSWs), are needed. Further data are required to evaluate antiretroviral efficacy in preventing HTLV-1 transmission from in vitro studies, animal models, and clinical cohorts. PrEP delivery programmes should consider prioritizing the long-acting injectable INSTI, cabotegravir, in HTLV-1 endemic settings.

Cell Culture Evaluation Suggests Widely Available HIV Drugs Will Make Effective HTLV-1 Prophylactics

“…The most transformative advance in PrEP is probably the advent of long-acting cabotegravir, which reduces the need for daily pill dosing to as few as six injections a year. There is little biological indication that current PrEP regimens would fail to protect persons at risk from contracting HTLV-1 49 . Ultimately, the target cells required for optimal drug function and the transmission via bodily fluids are shared between HIV and HTLV-1.…”

“…As such, in the absence of a vaccine, PrEP provides the only cost-effective option for stemming childhood infections and future caseloads of ATLL in lower-middle-income countries. If rolled out alongside campaigns to increase HTLV-1 awareness, it's likely clinically successful PrEP would drastically reduce sexual transmission rates, offering the first effective transmission barrier to condomless sex, through which 70% of new HTLV-1 cases occur 49,54 . Moreover, since sexual transmission is associated with myeloneuropathy prognosis, PrEP could prove an efficient measure in quelling HAM/TSP cases.…”

The slowdown of new infections by human retroviruses has reached a plateau in Spain

“…HTLV‐1 was mostly found among Latin American male, mostly men who had sex with men. At this time, it is unclear in what extent the use of antiretrovirals to treat or prevent HIV‐1 contagion as PrEP might protect from sexual transmission of HTLV‐1 infection 54 . In vitro data support that cabotegravir may halt HTLV‐1 transmission 55 and long‐acting formulations of this drug are increasingly being used by persons engaged in high‐risk sexual behaviors.…”

“…At this it is unclear in what extent the use of antiretrovirals to treat or prevent HIV-1 contagion as PrEP might protect from sexual transmission of HTLV-1 infection. 54 In vitro data support that cabotegravir may halt HTLV-1 transmission 55 and long-acting formulations of this drug are increasingly being used by persons engaged in high-risk sexual behaviors. It should be noted that the extent of PrEP use in this population is still low in Spain compared to other Western European countries.…”

Pre-Exposure Prophylaxis for viral infections other than HIV

“…These HTLV-1 serosurveys should be performed to recover any evidence in favor of a protective effect of antiretrovirals on HTLV-1 acquisition. This information would be particularly relevant in cabotegravir users, since this drug has shown potent antiretroviral activity in vitro against HTLV-1 [37,38].…”