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| Lenacapavir and CAB-LA offer long-acting alternatives to daily oral PrEP for HIV prevention. |
For decades, HIV prevention has depended heavily on behavioural interventions, condoms and, more recently, medicines taken regularly as pre-exposure prophylaxis (PrEP).
PrEP changed HIV prevention by allowing an HIV-negative person to take antiretroviral medicine before exposure to substantially reduce the chance of acquiring HIV.
But daily tablets have an obvious limitation: they have to be taken consistently.
For some people, remembering a tablet every day is difficult. Others may worry about privacy, stigma, travelling with medication or having family members or partners discover their PrEP.
Long-acting HIV prevention is beginning to change that equation.
Two medicines are particularly important:
long-acting injectable cabotegravir (CAB-LA) and long-acting injectable lenacapavir (LEN).
CAB-LA can provide protection through injections approximately every two months, while lenacapavir can be administered only twice a year.
Both have demonstrated remarkable efficacy in large clinical trials, and the World Health Organization now recommends both as additional PrEP options within combination HIV prevention.
But they are different medicines, work differently and should not be confused.
Here is what you need to know.
First, What Is PrEP?
PrEP means pre-exposure prophylaxis.
It is HIV prevention medication used by people who do not have HIV but may have ongoing or future exposure to the virus.
PrEP is different from treatment for people already living with HIV.
It is also different from post-exposure prophylaxis (PEP), which is an emergency intervention started after a possible HIV exposure.
PrEP works by maintaining antiretroviral medicine in the body so that HIV has difficulty establishing a permanent infection if exposure occurs.
Daily oral PrEP has been highly effective when taken correctly.
The development of long-acting PrEP does not mean oral PrEP has stopped working.
Instead, it gives people something HIV prevention programmes have needed for a long time:
choice.
Some people may prefer tablets.
Others may prefer an injection every two months.
And some may find receiving an injection only twice a year far more convenient.
WHO considers expanding PrEP choice an important way of increasing uptake and effective use of HIV prevention.
Read the WHO guidance on available PrEP approaches.
What Is CAB-LA?
CAB-LA stands for long-acting cabotegravir.
Cabotegravir belongs to a class of HIV medicines called integrase strand-transfer inhibitors, or INSTIs.
HIV needs an enzyme called integrase to insert its genetic material into human cells as part of establishing infection.
Cabotegravir inhibits this process.
The long-acting formulation allows the medicine to remain active in the body for an extended period after injection.
For HIV prevention, CAB-LA is administered as a deep intramuscular injection, generally in the gluteal muscle.
After initiation, injections are usually given every eight weeks.
WHO recommended CAB-LA in 2022 as an additional HIV prevention option for people at substantial risk of acquiring HIV.
Read the WHO guideline on long-acting injectable cabotegravir.
How Effective Is CAB-LA?
The evidence behind CAB-LA came particularly from two major clinical trials:
HPTN 083 and HPTN 084.
HPTN 083
HPTN 083 compared long-acting cabotegravir with daily oral tenofovir disoproxil fumarate/emtricitabine, commonly abbreviated TDF/FTC.
The study included cisgender men who have sex with men and transgender women who have sex with men across several countries.
There were 13 HIV infections in the cabotegravir group compared with 39 in the TDF/FTC group during the primary analysis.
This corresponded to substantially lower HIV incidence among participants assigned to CAB-LA.
The results were published in the New England Journal of Medicine.
Read the HPTN 083 study in the New England Journal of Medicine.
HPTN 084
HPTN 084 examined CAB-LA among cisgender women, predominantly in sub-Saharan Africa.
It enrolled women in Botswana, Eswatini, Kenya, Malawi, South Africa, Uganda and Zimbabwe.
The study again demonstrated very strong protection.
During the primary analysis, four HIV infections occurred among women assigned CAB-LA compared with 34 among those assigned daily TDF/FTC.
The study therefore provided particularly important evidence that long-acting injectable PrEP can work extremely well for women in African settings.
Read the HPTN 084 study on PubMed.
Why Did CAB-LA Perform Better Than Daily Oral PrEP?
This needs careful interpretation.
The results do not mean oral PrEP is ineffective.
Daily oral PrEP is extremely effective when used consistently.
But medicines cannot provide their intended protection if they are not taken as required.
Long-acting injections reduce the number of times someone needs to remember to take HIV prevention medication.
Instead of remembering a tablet every day, a person receiving CAB-LA returns periodically for an injection.
This can reduce some adherence challenges.
It may also offer greater privacy for people who do not want to store HIV prevention tablets at home.
What Is Lenacapavir?
Lenacapavir, commonly shortened to LEN, represents another major development.
It is a long-acting antiretroviral medicine belonging to a different class from cabotegravir.
Lenacapavir is a capsid inhibitor.
The HIV capsid is a protein shell surrounding important viral genetic material and enzymes.
Lenacapavir interferes with the capsid at multiple stages of the HIV life cycle.
Its pharmacological properties allow it to remain active for an exceptionally long period.
For PrEP, long-acting lenacapavir is administered subcutaneously every 26 weeks, meaning approximately twice a year.
That is the feature that has attracted enormous global attention.
Instead of:
365 daily tablets a year
or approximately
six CAB-LA injection visits a year,
LEN can provide long-acting prevention through approximately:
two injection visits per year.
In July 2025, WHO recommended injectable lenacapavir as an additional HIV prevention option within combination HIV prevention programmes.
Read the WHO lenacapavir HIV prevention guideline.
How Effective Is Lenacapavir?
The pivotal evidence came from the PURPOSE programme, particularly PURPOSE 1 and PURPOSE 2.
The results were among the most impressive ever reported for biomedical HIV prevention.
PURPOSE 1: Lenacapavir Among Women in Africa
PURPOSE 1 enrolled adolescent girls and young women in South Africa and Uganda.
Participants received either twice-yearly lenacapavir or daily oral PrEP regimens.
Among 2,134 initially HIV-negative participants receiving lenacapavir, there were zero HIV infections during the primary analysis.
That represented 100% observed efficacy against HIV acquisition during the analysed period.
The result was striking because young women in parts of sub-Saharan Africa continue to experience disproportionate HIV risk.
The study was published in the New England Journal of Medicine.
Read the PURPOSE 1 trial in the New England Journal of Medicine.
It is important to understand what "100% efficacy" means here.
It means no HIV infections were observed among participants receiving LEN during that study analysis.
It does not mean scientists should promise that no person using lenacapavir correctly will ever acquire HIV under every real-world circumstance.
Clinical-trial findings must always be interpreted within their study conditions and follow-up.
PURPOSE 2: Evidence Across Additional Populations
PURPOSE 2 expanded the evidence to cisgender men, transgender women, transgender men and gender-nonbinary people.
Among 3,265 participants included in the modified intention-to-treat analysis, there were two HIV infections in the lenacapavir group and nine among participants assigned daily F/TDF.
HIV incidence with LEN was significantly lower than both estimated background HIV incidence and incidence in the oral F/TDF comparison group.
Read the PURPOSE 2 results in the New England Journal of Medicine.
Together, PURPOSE 1 and PURPOSE 2 provided evidence across diverse populations and geographical settings.
LEN vs CAB-LA: What Is the Difference?
The easiest way to understand the two options is side by side.
| Feature | Lenacapavir (LEN) | Cabotegravir (CAB-LA) |
|---|---|---|
| Purpose discussed here | HIV PrEP | HIV PrEP |
| Drug class | Capsid inhibitor | Integrase inhibitor |
| Administration | Subcutaneous injection | Intramuscular injection |
| Maintenance interval | About every 26 weeks | About every 8 weeks |
| Approximate frequency | Twice yearly | About six times yearly after initiation |
| Major prevention trials | PURPOSE 1 & 2 | HPTN 083 & 084 |
| WHO recommendation | 2025 | 2022 |
| Daily tablet required long-term | No | No |
| Prevents other STIs | No | No |
| Prevents pregnancy | No | No |
Both are long-acting PrEP.
They simply achieve long-duration HIV prevention using different medicines and dosing schedules.
Is LEN Better Than CAB-LA?
It is tempting to look at the dosing schedule and immediately declare LEN the winner.
That would be premature.
LEN's twice-yearly schedule is undeniably attractive.
For someone who struggles with frequent clinic attendance, reducing prevention visits associated with injections could be extremely valuable.
But choosing PrEP is not simply about selecting the medicine with the longest interval.
Other considerations include:
availability,
national guidelines,
eligibility,
clinical history,
drug interactions,
testing requirements,
individual preference,
tolerability,
programme capacity,
cost,
and continuity of access.
CAB-LA also has several years of implementation experience and extensive evidence across populations.
The bigger achievement is therefore not necessarily that one medicine replaces another.
It is that HIV prevention is moving toward multiple effective options.
Why Long-Acting PrEP Could Matter So Much in Africa
Long-acting PrEP has particular relevance for sub-Saharan Africa.
The region continues to carry a disproportionate share of the global HIV burden.
And effective prevention is not only about whether a medicine works biologically.
People have to be able and willing to use it consistently.
Daily PrEP may present challenges including:
forgetting tablets,
fear that someone will discover the medication,
HIV-related stigma,
travel,
work schedules,
pill fatigue,
difficulty attending services,
and changes in perceived HIV risk.
Long-acting PrEP does not magically eliminate all these problems.
But it changes the burden of adherence.
Someone using twice-yearly LEN does not need to make a prevention decision every morning.
Someone using CAB-LA does not need to remember a daily pill.
That could make PrEP easier to integrate into people's lives.
Why This Matters for Adolescent Girls and Young Women
The African evidence is particularly important for adolescent girls and young women.
Young women in parts of eastern and southern Africa continue to experience HIV vulnerability shaped by overlapping biological, economic and social factors.
These can include unequal sexual relationships, gender-based violence, limited negotiating power around condom use and relationships with older partners.
PURPOSE 1 therefore matters for more than demonstrating that a new medicine works.
It shows that an HIV prevention method requiring only twice-yearly administration can achieve exceptionally high protection in a population for whom sustained use of prevention has historically been challenging.
What Could LEN and CAB-LA Mean for Nigeria?
Nigeria has one of the world's largest populations of people living with HIV in absolute numbers, despite having a lower national prevalence than several countries in eastern and southern Africa.
PrEP is already part of Nigeria's combination HIV prevention response.
Long-acting options could eventually broaden prevention choices for populations who may benefit from PrEP, including people with partners living with HIV who are not known to be virally suppressed, some key populations, people with recurrent sexual exposure to HIV and others assessed as having ongoing prevention needs.
But a WHO recommendation does not automatically mean that every clinic in Nigeria immediately has the medicine available.
Introducing a new biomedical intervention requires more than regulatory approval.
Programmes have to consider:
national policy,
regulatory authorization,
procurement,
price,
supply chains,
provider training,
HIV testing,
pharmacovigilance,
demand creation,
community acceptance,
data systems,
drug-resistance surveillance,
and sustainable financing.
For Nigeria and other African countries, the key question is therefore shifting from:
"Does long-acting PrEP work?"
to:
"How can people who would benefit actually get it safely, affordably and consistently?"
HIV Testing Remains Essential
Long-acting PrEP should only be used by someone who does not have HIV.
This makes HIV testing critically important before initiation and during continued use.
Why?
Because PrEP medicines are designed for prevention, not as complete treatment regimens for established HIV infection.
If someone unknowingly acquires HIV and continues receiving a PrEP medicine alone, the virus may be exposed to inadequate treatment.
That creates an opportunity for drug resistance.
WHO's 2025 guidance therefore addressed HIV testing specifically for people initiating or continuing long-acting injectable PrEP.
Importantly, WHO supports the use of HIV rapid diagnostic tests within these programmes rather than making access dependent on complex laboratory testing in every setting.
Read WHO's guidance on HIV testing for long-acting injectable PrEP.
The Long Pharmacological 'Tail'
Long-acting medicines introduce another important issue.
After someone stops injections, the medicine does not disappear from the body immediately.
Drug concentrations gradually decline over time.
This period is sometimes called the pharmacokinetic tail.
Eventually, drug levels may become too low to provide reliable HIV prevention while still being high enough to expose HIV to the drug if infection occurs.
This creates theoretical and observed concerns about resistance.
People discontinuing long-acting PrEP therefore need appropriate counselling and may need another effective PrEP option during periods of continuing HIV exposure.
This is one reason long-acting PrEP should be delivered as a programme of care rather than treated as simply "get an injection and forget about HIV."
Drug Resistance Matters
Resistance deserves particular attention with both medicines.
CAB-LA is an integrase inhibitor.
If HIV infection develops while cabotegravir concentrations are present, resistance mutations affecting integrase inhibitors can sometimes emerge.
HPTN 083 documented delayed detection of some HIV infections and integrase resistance among some participants who acquired HIV after CAB-LA exposure.
Lenacapavir resistance is also an important implementation consideration because it belongs to the relatively new capsid-inhibitor class.
WHO's LEN guideline specifically considers resistance and recommends surveillance as long-acting PrEP is scaled up.
This doesn't make either drug unsafe or ineffective.
It explains why regular HIV testing and appropriate follow-up remain essential even when injections are required only occasionally.
What Are the Side Effects?
Both medicines can cause side effects.
CAB-LA
Injection-site reactions are common with CAB-LA.
These may include:
pain,
swelling,
redness,
or discomfort at the injection site.
In HPTN 083, injection-site reactions were frequently reported, although discontinuation because of these reactions was uncommon.
Lenacapavir
Injection-site reactions also occur with LEN.
In PURPOSE 1, injection-site reactions were more common among people receiving LEN than among participants receiving placebo injections, although very few discontinued LEN because of them.
PURPOSE 2 similarly found that discontinuation because of injection-site reactions was uncommon.
People considering either option should discuss expected side effects and relevant medical conditions with a qualified healthcare provider.
Do LEN and CAB-LA Prevent Other Sexually Transmitted Infections?
No.
This is extremely important.
PrEP protects against HIV.
It does not prevent:
gonorrhoea,
syphilis,
chlamydia,
hepatitis C,
human papillomavirus,
or most other sexually transmitted infections.
Long-acting PrEP also does not prevent pregnancy.
Condoms therefore continue to have value even for someone using highly effective PrEP.
Sexual-health services should ideally integrate PrEP with STI screening, condoms, contraception where desired, hepatitis services and other relevant prevention interventions.
Does PrEP Still Matter if a Partner With HIV Is Undetectable?
This requires an important distinction.
A person living with HIV who takes effective antiretroviral therapy and maintains an undetectable viral load does not sexually transmit HIV.
This is the principle known as U=U: Undetectable = Untransmittable.
AnjKreb explains the evidence and implications in:
Viral Suppression and U=U: What an Undetectable HIV Viral Load Means.
PrEP may still be chosen depending on individual circumstances, other partners, uncertainty about viral suppression or personal preference.
But people should not be told that a consistently virally suppressed partner poses ongoing sexual HIV transmission risk.
U=U is one of the most important achievements of modern HIV treatment.
PrEP Is Prevention. ART Is Treatment.
Another common source of confusion is the relationship between PrEP and antiretroviral treatment.
LEN and CAB-LA in this article are being discussed as HIV prevention options for people without HIV.
People who have HIV require a complete antiretroviral treatment regimen.
AnjKreb explains modern HIV treatment in:
Antiretroviral Treatment for HIV: How ART Works and What Patients Should Expect.
There is an important complication in terminology.
Lenacapavir also has a role in HIV treatment in specific circumstances, but it is used as part of an appropriate combination regimen rather than alone.
Similarly, cabotegravir can be used with long-acting rilpivirine as a treatment option for selected people living with HIV.
Those treatment uses should not be confused with LEN or CAB-LA used as PrEP.
Long-Acting PrEP Does Not Replace Other HIV Prevention
No single intervention will end HIV transmission everywhere.
Long-acting PrEP should sit within combination HIV prevention.
Depending on someone's circumstances, that may include:
HIV testing,
condoms,
oral or injectable PrEP,
PEP following qualifying recent exposure,
ART for people living with HIV,
viral suppression and U=U,
STI prevention and treatment,
harm-reduction services,
prevention of mother-to-child transmission,
and interventions addressing sexual and gender-based violence.
The point of LEN and CAB-LA is not to make these interventions obsolete.
It is to add powerful new choices.
What Could Stop Long-Acting PrEP From Reaching the People Who Need It?
Scientific success does not automatically become public-health success.
The history of global health contains many effective medicines that remained inaccessible to the people who needed them most.
Long-acting PrEP faces several implementation challenges.
Cost
Countries and donors need prices that allow large-scale programmes to be sustained.
A medicine that works extraordinarily well but is unaffordable to health systems will have limited population impact.
Supply
Reliable manufacturing and procurement are necessary.
Missing a scheduled injection because a clinic has no stock undermines the advantages of a long-acting product.
Clinic capacity
Health workers need training in counselling, testing, injection administration, side-effect management and follow-up.
Demand and awareness
People cannot choose a prevention method they don't know exists.
Communities need accurate information that avoids both exaggerated promises and unnecessary fear.
Stigma
Long-acting products may reduce the visibility associated with storing PrEP tablets, but receiving injections through HIV services can still carry stigma.
Equity
Urban populations and people attending well-funded programmes should not be the only beneficiaries.
A successful African rollout has to consider rural communities, adolescents, key populations and people who face barriers to conventional health services.
Could Long-Acting PrEP Change the HIV Epidemic?
Potentially, yes.
But the answer depends on implementation.
The efficacy demonstrated in clinical trials is extraordinary.
The next challenge is effective coverage.
A medicine cannot prevent HIV while sitting in a warehouse.
It cannot protect someone who cannot afford it.
It cannot overcome an HIV testing system that turns people away.
And it cannot solve stigma by itself.
The real public-health impact of LEN and CAB-LA will depend on whether countries can convert biomedical innovation into accessible prevention.
That means the next phase of the story belongs not only to pharmaceutical science.
It belongs to health systems.
Frequently Asked Questions
Is lenacapavir a vaccine?
No.
Lenacapavir is an antiretroviral medicine used for long-acting HIV prevention. It does not train the immune system in the way a vaccine does.
Is CAB-LA an HIV vaccine?
No.
CAB-LA is also antiretroviral PrEP, not a vaccine.
How often is lenacapavir given for PrEP?
Long-acting LEN for PrEP is administered approximately every 26 weeks, or twice yearly.
How often is CAB-LA given?
Following initiation, CAB-LA maintenance injections are generally administered every eight weeks.
Can someone with HIV use LEN or CAB-LA as PrEP?
No.
PrEP is for people who do not have HIV.
People diagnosed with HIV require a complete HIV treatment regimen selected by qualified healthcare professionals.
Which is better, LEN or CAB-LA?
Both are highly effective long-acting HIV prevention options.
LEN has the major convenience advantage of twice-yearly dosing, while CAB-LA has been recommended by WHO since 2022 and has accumulated more implementation experience.
The best option depends on availability, eligibility, preference and clinical circumstances.
Can I stop using condoms after starting injectable PrEP?
PrEP provides highly effective protection against HIV when used correctly, but it does not prevent most other sexually transmitted infections or pregnancy.
Condom decisions therefore involve more than HIV prevention alone.
Do I still need HIV tests if my injection lasts for months?
Yes.
HIV testing remains an essential part of safely initiating and continuing long-acting PrEP.
Is long-acting PrEP currently available everywhere in Africa?
No.
Availability varies substantially between countries and programmes. WHO recommendation is an important step, but national regulatory decisions, guidelines, procurement, pricing and programme rollout determine actual access.
The Bottom Line
HIV prevention is entering a different era.
Daily oral PrEP proved that antiretroviral medicines could prevent HIV acquisition extremely effectively when taken consistently.
CAB-LA reduced the burden of daily adherence by offering long-acting injections approximately every two months.
Lenacapavir has pushed that idea even further:
one injection cycle approximately every six months.
The clinical evidence is exceptionally strong.
PURPOSE 1 observed no HIV infections among 2,134 participants receiving twice-yearly lenacapavir during its primary analysis.
PURPOSE 2 demonstrated very low HIV incidence across additional populations.
HPTN 083 and HPTN 084 demonstrated that CAB-LA was superior to daily oral TDF/FTC in the populations studied.
But perhaps the biggest development is not simply the performance of one drug.
It is choice.
HIV prevention can increasingly be adapted to people's lives rather than expecting every person to adapt to one prevention method.
For Nigeria and the rest of Africa, the scientific question is increasingly being answered.
The next question is harder:
Can health systems make these breakthroughs accessible to the people who need them most?
That is where the next chapter of long-acting HIV prevention will be written.
References and Further Reading
World Health Organization. Guidelines on lenacapavir for HIV prevention and testing strategies for long-acting injectable PrEP.
https://www.who.int/publications/i/item/9789240111608
World Health Organization. Guidelines on long-acting injectable cabotegravir for HIV prevention.
https://www.who.int/publications/i/item/9789240054097
Bekker LG, et al. Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women. New England Journal of Medicine.
https://www.nejm.org/doi/full/10.1056/NEJMoa2407001
Kelley CF, et al. Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons. New England Journal of Medicine.
https://www.nejm.org/doi/10.1056/NEJMoa2411858
Landovitz RJ, et al. Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women. New England Journal of Medicine.
https://www.nejm.org/doi/full/10.1056/NEJMoa2101016
Delany-Moretlwe S, et al. Cabotegravir for the Prevention of HIV-1 in Women: Results from HPTN 084. The Lancet.
https://pubmed.ncbi.nlm.nih.gov/35378077/
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