Michael Gwarisa
Zimbabwe has set the stage for the rollout of Lenacapavir, a long acting injectable HIV prevention medicine that is expected to significantly strengthen the country’s HIV response. The injectable drug, which is administered only twice a year, is being introduced as part of Zimbabwe’s expanded HIV prevention strategy targeting people at high risk of new infections.
According to the Ministry of Health and Child Care, an estimated 46,000 people will be prioritised during the initial phase of the rollout. These individuals have been identified in districts experiencing persistently high or rising HIV incidence rates.
The national rollout is scheduled to begin on February 19, 2026, following the official launch in Harare at Epworth Polyclinic. Implementation will initially focus on major urban centres including Bulawayo, Gweru, Masvingo, Mutare and Chitungwiza, before expanding to other districts such as Karoi, Mazowe, Tsholotsho, Kwekwe, Shamva and Gwanda. To support the programme, approximately 400 healthcare workers have already been trained to administer PrEP and manage recipients, including monitoring and responding to any adverse events.
Addressing Longstanding Questions Around HIV Prevention
For years, questions surrounding biomedical HIV prevention tools have largely focused on two issues: how effective they are at preventing new infections and whether they cause side effects that could affect long term use. Zimbabwe currently offers several PrEP options, including oral PrEP, the dapivirine vaginal ring and long acting injectable cabotegravir, commonly known as CAB LA.
Lenacapavir enters this landscape with significant scientific backing. Clinical trials of lenacapavir, branded as YEZTUGO, were conducted across diverse populations and compared HIV infection rates in two key ways. Researchers measured outcomes against background HIV incidence rates and against rates among participants receiving TDF based oral PrEP.
Across these studies, lenacapavir demonstrated exceptional effectiveness in preventing HIV infection.
What the Clinical Evidence Shows
Dr Byron Chingombe, a consultant involved in Zimbabwe’s PrEP programme, told clinicians during a recent technical meeting that lenacapavir had undergone rigorous testing and emerged as a highly effective HIV prevention tool.
The results were striking. Among women, the HIV infection rate was 100 percent lower than the background HIV incidence and 100 percent lower than among those receiving TDF based oral PrEP. Among men, transgender women, transgender men and gender nonbinary persons, the HIV infection rate was 96 percent lower than background HIV incidence and 89 percent lower than among those receiving oral PrEP.
Large scale efficacy trials further reinforced these findings. In the PURPOSE 1 trial, which enrolled adolescent girls and young women aged 16 to 25 years in South Africa and Uganda, there were zero incident HIV infections among participants who received lenacapavir, translating to 100 percent efficacy.
The PURPOSE 2 trial enrolled cisgender men, transgender women, transgender men and gender nonbinary people aged 16 years and older who have sex with male partners across seven countries. This study recorded only two HIV infections in the lenacapavir group, representing a 96 percent reduction compared to background HIV incidence.
In addition to its high effectiveness, lenacapavir demonstrated strong tolerability. Only about one percent of participants discontinued treatment due to injection site reactions across trials. Adherence and continuation rates were also high, an important consideration for real world HIV prevention programmes.
How Lenacapavir Is Started and Maintained
Starting lenacapavir involves a structured initiation regimen that combines oral tablets and injections. According to Dr Chingombe, this initiation phase is essential to ensure the drug reaches adequate levels in the body quickly.
On Day 0, a healthcare provider administers two lenacapavir injections at separate injection sites. On the same day, the client takes two oral lenacapavir tablets and is given two additional tablets to take at home the following day. On Day 1, the client takes the remaining two tablets orally, completing the initiation regimen.
Once this initiation phase is completed, ongoing protection is maintained through follow up injections administered every six months, or every 26 weeks. A scheduling window of plus or minus 14 days is allowed for each follow up injection, offering flexibility while maintaining protection.
How Lenacapavir Works in the Body
Lenacapavir belongs to a new class of HIV medicines known as capsid inhibitors and is the first drug of its kind to be used for HIV prevention. The capsid is the protein shell that encases the virus’s genetic material.
Lenacapavir disrupts the HIV lifecycle at multiple stages. It over stabilises the incoming viral capsid, making it brittle and prone to premature rupture. This causes the virus’s genetic material to be released before it can enter the cell nucleus. The drug also interferes with the formation of new capsids during viral assembly, resulting in defective viral particles that are unable to infect other cells.
This multi level mechanism helps explain the drug’s high effectiveness and durability.
Side Effects of Lenacapavir
As with any medication, lenacapavir can cause side effects, and healthcare workers are encouraged to monitor and report any adverse reactions. Most side effects observed during clinical trials were mild to moderate in severity.
During the PURPOSE 1 and PURPOSE 2 trials, injection site reactions were the most commonly reported adverse events among participants receiving YEZTUGO and those receiving TRUVADA as a comparator.
In PURPOSE 1, injection site reactions occurred in 69 percent of participants receiving YEZTUGO, compared with 34 percent among those receiving TRUVADA. Other reported reactions included headache, nausea, dizziness, vomiting and diarrhoea, with rates generally similar or lower in the YEZTUGO group compared to TRUVADA.
In PURPOSE 2, injection site reactions were reported in 83 percent of participants receiving YEZTUGO and 69 percent of those receiving TRUVADA. Rates of other adverse reactions were lower overall. Headache was reported in two percent of participants in both groups, nausea in two percent of the YEZTUGO group versus four percent of the TRUVADA group, dizziness and vomiting in less than one percent versus one percent, and diarrhoea in two percent of participants in both groups.
These figures reflect all adverse events attributed to the study drug or, in the case of injection site reactions, the injection procedure itself. Participants in the TRUVADA group received placebo subcutaneous injections.
A Major Step Forward for HIV Prevention
As Zimbabwe prepares to roll out lenacapavir nationally, the evidence points to a highly effective, safe and user friendly HIV prevention option that could reshape how PrEP is delivered. With twice yearly dosing, strong adherence and exceptional efficacy, lenacapavir has the potential to reduce new infections, particularly among populations that face challenges with daily or monthly prevention methods.
