PrEP: HIV Prevention Explained

This article is educational content based on current peer-reviewed guidelines, including the Southern African HIV Clinicians Society 2025 PrEP Guideline, the IAS-USA 2024 Recommendations, and the USPSTF 2023 Grade A recommendation on PrEP. It is not personalised medical advice. PrEP decisions depend on individual circumstances and should be made in consultation with a healthcare provider.

Ready to talk about PrEP? Book a consultation with Dr Chellan.

What PrEP is

PrEP stands for pre-exposure prophylaxis. It is antiretroviral medication taken by people who do not have HIV, to prevent HIV infection if they are exposed to the virus.

The principle is simple. If you have protective levels of antiretroviral medication in the tissues where HIV would try to establish infection, the lining of the rectum, the vagina, or the bloodstream, then when HIV enters the body the drug blocks it from replicating and gaining a foothold. The immune system clears what is left before a persistent infection can form.

PrEP is not a vaccine. It does not train the immune system to recognise HIV. It works only while you are taking it. Protection fades when the drug clears.

Oral PrEP was first approved for HIV prevention in 2012. South Africa introduced it in the public sector in 2016. By the end of 2024, over 1.78 million people had started oral PrEP across approximately 4,291 public-sector facilities in SA. That is one of the largest PrEP programmes in the world.

Who should consider PrEP

Both the SAHCS 2025 Guideline and the USPSTF 2023 Grade A recommendation are clear: PrEP should be offered to anyone who requests it, as well as to people likely to be exposed to HIV.

This is a deliberate shift from the earlier era, when eligibility was based on specific risk behaviours and risk calculators. That approach was abandoned because it created barriers for people who would benefit, failed to capture individual risk perception, stigmatised PrEP-seeking behaviour, and missed people at risk who did not fit narrow criteria.

The current framing: you know your own situation better than a risk calculator does. If you are thinking about PrEP, that is itself a valid reason to have the conversation.

People who commonly benefit from PrEP include:

• Sexually active people without consistent condom use
• People whose sexual partner has HIV and is not virally suppressed, or whose status is unknown
• People in a serodifferent relationship (one partner with HIV, the other without)
• Men who have sex with men, particularly with ongoing exposure
• People who have had a recent sexually transmitted infection
• People considering or recently completing post-exposure prophylaxis (PEP) with ongoing risk
• People who inject drugs and may share equipment
• Sex workers
• People who have been in situations of sexual assault where ongoing risk remains
• People planning to conceive with a partner who has HIV
• Anyone who feels they might be exposed to HIV and wants protection

You do not need to disclose specific behaviours to request PrEP. A conversation about PrEP is standard primary care.

How well PrEP works

PrEP efficacy depends almost entirely on taking the medication as prescribed. When it is taken consistently, it is highly effective.

Oral PrEP (tenofovir with emtricitabine):

• The iPrEx trial (2,499 men who have sex with men and transgender women) showed a 44% reduction in HIV on intent-to-treat analysis, and close to 100% effectiveness in participants with blood levels indicating daily use.
• The Partners PrEP trial (4,747 heterosexual serodifferent couples in Kenya and Uganda) showed a 75% reduction with TDF/FTC versus placebo.
• The IPERGAY trial (men who have sex with men using event-driven 2-1-1 dosing) showed an 86% reduction.
• Pooled analyses show HIV incidence of 0.13 per 100 person-years with high adherence, rising to 1.27 per 100 person-years with low adherence, a nearly tenfold difference driven entirely by consistency.

Long-acting cabotegravir (CAB-LA):

• HPTN 083 (4,566 cisgender men who have sex with men and transgender women): CAB-LA reduced HIV risk by 67% compared with daily oral PrEP.
• HPTN 084 (3,178 cisgender women in sub-Saharan Africa, including South Africa): CAB-LA reduced HIV risk by 89% compared with daily oral PrEP.

Lenacapavir (six-monthly injection):

• PURPOSE 1 (2,134 cisgender women in Southern and Eastern Africa, including SA): zero HIV infections in the lenacapavir group, 100% effective in the trial.
• PURPOSE 2 (2,183 cisgender men, transgender, and nonbinary participants): only two HIV infections in the lenacapavir group, a 96% reduction versus background incidence.

All approved PrEP methods work. The practical difference is that long-acting options remove the daily adherence challenge that limits real-world oral PrEP effectiveness.

Oral PrEP: the standard option

For most patients in South Africa in 2026, "PrEP" means oral PrEP. The other options are real, coming, and genuinely useful for specific patients, but oral PrEP is what most people actually take.

What it is. One tablet daily, containing tenofovir disoproxil fumarate (TDF) 300 mg plus emtricitabine (FTC) 200 mg. These are two of the same antiretroviral medications used to treat HIV, combined into a fixed-dose tablet.

Who can take it. Anyone weighing at least 30 kg, which includes most adolescents and all adults. Approved for men, women, transgender and gender-diverse people, people who inject drugs, and pregnant or lactating people.

Effectiveness. Between 90% and 99% when taken consistently as prescribed.

Time to protection.

• Rectal exposure (anal sex): within 24 hours when initiated with a double starter dose (two tablets on day 1, then one daily).
• Vaginal exposure and injection drug use: seven days of daily dosing.

Stopping safely.

• After the last rectal exposure: continue for two more doses.
• After the last vaginal exposure: continue daily for seven more days.
• Injection drug use: seven more days after the last shared exposure.

Contraindications.

• Known or suspected HIV infection (ART, not PrEP, is required).
• Allergy or hypersensitivity to tenofovir or emtricitabine.
• Weight under 30 kg.
• Reduced kidney function: eGFR below 50 mL/min in adults, or below 80 mL/min at 10 to 16 years of age.
• In pregnancy, a baseline serum creatinine above 85 μmol/L.

A note on hepatitis B. Tenofovir and emtricitabine are also active against hepatitis B. Stopping oral PrEP abruptly in someone with chronic hepatitis B can cause a hepatitis flare, and specialist input is needed if this applies to you.

Event-driven 2-1-1 dosing

For people assigned male at birth who are not on gender-affirming hormone therapy, oral PrEP can be taken around specific sexual encounters rather than daily. This is called 2-1-1 dosing, or event-driven PrEP.

How it works:

1. Two tablets, 2 to 24 hours before sex.
2. One tablet, 24 hours after the first dose.
3. One tablet, 24 hours after the second dose.
4. If more sex happens, continue one tablet daily, stopping two days after the last sexual activity.

Effectiveness: in the IPERGAY trial, 2-1-1 dosing gave an 86% reduction in HIV incidence.

Important limitations per SAHCS 2025:

• Only for penile or anal exposure. There is no evidence for vaginal or neovaginal sex.
• Not protective against HIV transmission through injection drug use.
• Only for people assigned male at birth who are not on feminising hormone therapy. Transgender women on hormones should use daily dosing.
• Requires being able to plan sex at least two hours in advance, unless the loading dose is already in the system.

For many patients, 2-1-1 dosing is a more acceptable option than daily tablets. Dr Chellan can discuss whether it is appropriate for your situation.

Long-acting options: DVR, CAB-LA, and lenacapavir

Three long-acting HIV prevention methods are now approved internationally. All three are available in principle in SA, with real-world access that varies by product.

Dapivirine vaginal ring (DVR)

A flexible silicone ring containing 25 mg of the antiretroviral dapivirine, inserted into the vagina and releasing a steady low dose over 28 days.

• For people assigned female at birth, 18 years and older.
• Effectiveness is moderate: around 31% overall risk reduction, with 63% risk reduction per sex act when the ring is in place and used consistently. Less effective than oral PrEP or CAB-LA. Best used alongside condoms.
• Left in place for 28 days. No need to remove during sex or menstruation. Replaced monthly.
• Very low systemic absorption, so systemic side effects are minimal.
• Only protects the vagina, not against HIV from anal sex or injection exposure. Not yet approved for use in pregnancy or lactation in SA, although safety data from DELIVER and other studies are reassuring and a SAHPRA decision is pending.
• SAHPRA-approved in 2022. Public-sector rollout limited to pilot sites. Some private-sector access in major centres.

Long-acting cabotegravir (CAB-LA)

A long-acting injectable integrase inhibitor, 600 mg given as an intramuscular gluteal injection.

• Two initiation injections one month apart, then a continuation injection every two months. A seven-day flexibility window is permitted before or after each due date.
• At least 90% effective when received on schedule, and possibly as high as 100% in trials. In HPTN 084 (cisgender women in sub-Saharan Africa), CAB-LA was 89% more effective than daily oral PrEP.
• Every two months versus every day. Eliminates daily adherence as a factor. Real-world effectiveness is higher than oral PrEP largely for that reason.

Considerations specific to CAB-LA:

• Long pharmacokinetic tail. After the last injection, cabotegravir is detectable for up to 12 months. If someone acquires HIV during the tail period, there is a risk of developing drug resistance that could affect future HIV treatment. Alternative PrEP (usually oral PrEP) is recommended for 12 months after stopping CAB-LA.
• Baseline HIV testing is critical, and where resources allow, HIV NAAT testing is considered at initiation to rule out acute HIV that might not yet show on rapid tests. Starting CAB-LA with undiagnosed HIV can lead to LEVI syndrome (long-acting early viral inhibition), where the drug partially suppresses viraemia, delays diagnosis, and can lead to integrase inhibitor resistance.
• HIV self-testing is not recommended for CAB-LA monitoring, unlike oral PrEP and DVR. Provider testing is required.
• Contraindicated in people weighing under 35 kg, with acute hepatitis or advanced liver disease, or on certain anti-epileptic or TB medications (carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampicin, rifapentine).
• Injection-site reactions are common (pain, redness, swelling), usually mild, and reduce with subsequent injections.

SAHPRA-approved in 2022. Public-sector scale-up is still limited. Private-sector access depends significantly on medical aid reimbursement. Generic licensing through the Medicines Patent Pool, for PrEP use, is expected from approximately 2027.

Lenacapavir

A first-in-class capsid inhibitor given as a subcutaneous injection every six months.

• In the PURPOSE 1 trial (cisgender women in Southern and Eastern Africa, including SA), zero HIV infections occurred among 2,134 women on lenacapavir. In PURPOSE 2 (men, transgender, and nonbinary participants), only two HIV infections occurred among 2,183 participants, a 96% reduction versus background rates.
• FDA-approved for PrEP in June 2025. The IAS-USA 2024 Recommendations support lenacapavir for all sexual routes of HIV exposure once regulatory pathways are established in a given country.
• SA regulatory approval and access pathway are still being established. Not yet widely available. Generic licensing for PrEP use is expected from approximately late 2027.

Lenacapavir is the most effective HIV prevention intervention ever studied in a randomised trial. Its potential impact in SA, particularly for adolescent girls, young women, and key populations, is substantial. Availability is likely to expand over the next two to three years. As of 2026, it is not yet a day-to-day clinical option in George.

Monitoring on PrEP

Before starting PrEP, a short set of baseline tests is done. These are designed to exclude current HIV infection, identify anything that changes which PrEP option is safest, and establish baseline health.

For oral PrEP:

• HIV test, which must be negative. Fourth-generation lab test preferred; a rapid point-of-care test is also valid.
• Hepatitis B surface antigen and antibody status, because tenofovir also treats hepatitis B.
• Serum creatinine and eGFR for kidney function.
• STI screening: syphilis serology, and gonorrhoea and chlamydia NAAT (three-site where appropriate).
• Pregnancy test for people of childbearing potential.
• Hepatitis C antibody if risk factors are present.
• Hepatitis A antibody to determine vaccination need.

For DVR: HIV test, and assessment for vaginal ulceration or severe discharge (which would delay use until resolved).

For CAB-LA:

• HIV test, fourth-generation and ideally HIV NAAT.
• Hepatitis B and C screening.
• Liver function tests (particularly if hepatitis B-positive).
• Review of concurrent medications for drug interactions.
• Assessment for gluteal implants or fillers (relative caution).

Per SAHCS 2025, testing availability should not be a barrier to starting PrEP. In most cases, oral PrEP can be started the same day as the consultation, with test results reviewed at the follow-up visit a month later.

Follow-up schedule.

For oral PrEP and DVR:

• One month after starting: check-in, side-effect review, repeat HIV test.
• Every three months after that: HIV test, STI symptom screen, pregnancy test where applicable.
• Every six to twelve months: kidney function check (for oral PrEP).
• STI testing (gonorrhoea, chlamydia, syphilis) every six months if asymptomatic, or immediately on symptoms.

For CAB-LA:

• One month after starting: second injection and HIV test.
• Every two months after that: injection and HIV test (plus NAAT where available).
• STI testing on the same schedule as oral PrEP.

Each visit includes HIV testing before the next dose, assessment for side effects and effective use, review of any interim issues or new medications, an STI symptom screen, pregnancy testing where relevant, and reinforcement that PrEP does not prevent STIs or pregnancy. It is also the time to check whether PrEP is still what you want, or whether switching methods would suit your circumstances better.

Side effects

Oral PrEP (TDF/FTC).

• Most side effects are mild and resolve in the first two to four weeks.
• Common: nausea, abdominal cramping, decreased appetite, mild diarrhoea, flatulence, headache, dizziness.
• Less common but monitored: small reductions in bone mineral density (about 1% at hip and spine over the first year, then stabilising), and mild reversible changes in kidney function.
• Rare: proximal renal tubulopathy or Fanconi syndrome, very uncommon and reversible on stopping.
• In chronic hepatitis B, abrupt cessation of oral PrEP can cause a hepatitis flare, and specialist discussion is required.

DVR. Usually mild and experienced by relatively few users. Occasional vaginal discomfort, discharge, urinary tract infections, or abdominal pain. Very low systemic absorption means systemic side effects are minimal.

CAB-LA. Injection-site reactions are the most common side effect (pain, redness, swelling, induration), usually mild to moderate and decreasing with subsequent injections. Headache, nausea, diarrhoea, and fatigue occur in a minority.

Lenacapavir. Injection-site reactions are likely more common than with oral PrEP. Discontinuation due to side effects was rare in the PURPOSE trials.

If side effects become difficult on any method, contact the practice. There are usually practical options to manage them, including adjusting when you take the tablet, managing symptoms with simple interventions, or occasionally switching methods.

PrEP in pregnancy and breastfeeding

This is a major shift in SA guidance in the 2020s. PrEP is now actively recommended for pregnant and lactating people at risk of HIV exposure, because pregnancy is a time of more than doubled HIV acquisition risk, and an HIV infection acquired during pregnancy carries a high risk of transmission to the infant.

Options in pregnancy and lactation, per SAHCS 2025:

• Oral PrEP (TDF/FTC) is safe and recommended. A recent systematic review identified 14 studies evaluating outcomes with oral PrEP in pregnancy; none showed differences in pregnancy or perinatal outcomes.
• CAB-LA can be used following risk-benefit counselling. Growing safety data from HPTN 084 extension studies show no increase in congenital abnormalities. Breast-milk exposure is expected to be minimal.
• DVR is not yet SAHPRA-approved for pregnancy in SA, although evidence suggests it is safe. A regulatory decision is pending.
• Lenacapavir safety data are still accumulating. Participants in PURPOSE 1 who became pregnant did well, but a formal pregnancy indication is not yet established.

Common side effects of oral PrEP (nausea, abdominal cramps, fatigue) can overlap with early pregnancy symptoms. This is worth knowing so it does not get confused.

For serodifferent couples planning pregnancy, PrEP for the HIV-negative partner combined with viral suppression in the HIV-positive partner (see Living with HIV, long-term management) allows safer conception. This is a specific consultation, and Dr Chellan can discuss the safest approach for your situation.

Starting, stopping, and switching

PrEP does not need to be a lifelong commitment. Current SAHCS 2025 framing is explicit: people can start, stop, and restart PrEP throughout life as their circumstances change.

Starting. Same-day initiation after baseline HIV testing and counselling is the standard where clinically appropriate. Protection develops over seven days, or 24 hours with a double starter dose for anal exposure.

Stopping safely.

• After the last rectal exposure on oral PrEP: continue for two more doses.
• After the last vaginal exposure on oral PrEP: continue daily for seven days.
• After the last CAB-LA injection: protection continues for about eight weeks and then wanes. If ongoing risk continues, bridge with oral PrEP for 12 months.
• DVR: protection ends when the ring is removed. Condoms or alternative PrEP are needed if risk continues.

Switching between methods. PrEP methods can be switched to fit changing lifestyle or preferences. The general principle is to cover the transition period where one method is wearing off and the new one is kicking in:

• Oral PrEP to CAB-LA: continue oral PrEP for seven days after the first CAB-LA injection.
• CAB-LA to oral PrEP: start oral PrEP eight weeks after the last CAB-LA injection; continue for up to 12 months (the cabotegravir tail).
• Oral PrEP to DVR: use oral PrEP for seven days after DVR insertion.
• DVR to oral PrEP: continue DVR or alternative prevention for seven days after starting oral PrEP.

Cycling CAB-LA on and off is not recommended, because the long tail makes repeated start-stop cycles risky for drug resistance if HIV is acquired during the waning period.

PEP and PrEP

PEP and PrEP are related but distinct.

• PEP (post-exposure prophylaxis) is a 28-day course of antiretrovirals taken *after* a possible HIV exposure, started within 72 hours. It is an emergency intervention. See our PEP article for detail.
• PrEP is ongoing antiretroviral medication taken *before* exposure by people at ongoing risk.

PEP to PrEP transition (SAHCS 2025). For people who have just completed PEP and have ongoing risk of HIV exposure, PrEP can be started immediately after the 28-day PEP course, once HIV-negative status has been confirmed. No gap is needed. The four to six week PEP follow-up visit is the right time to have this conversation.

PrEP to PEP. If someone on PrEP has been fully adherent, PEP is usually not required after a further exposure, because PrEP is already providing protection. If there are adherence concerns or missed doses, it may be safer to pause PrEP and start a full PEP course to ensure protection.

Dr Chellan can advise on which approach is appropriate for your specific situation.

Access in South Africa

Public sector. Oral PrEP is free at primary health clinics nationally. The public sector offered oral PrEP at approximately 4,291 facilities by December 2024, reaching around 96% of primary health facilities. It is delivered through the Nurse-Initiated and Managed Antiretroviral Therapy (NIMART) programme, in which nurses prescribe and manage PrEP. Services are integrated with STI screening, contraception, TB screening, and family planning. DVR and CAB-LA access in the public sector is currently limited to pilot sites.

Private sector, including NeoHealth. Oral PrEP is widely available through private GPs. It is typically covered by medical aid schemes as a preventive benefit, with specific coverage varying. DVR is increasingly available in private practice. CAB-LA access depends on medical aid reimbursement; generic versions are expected in coming years.

In George specifically. Dr Chellan offers oral PrEP initiation and ongoing management at NeoHealth (Suite 12, Prince Vintcent Square, Gloucester Avenue, George Central), with access to DVR and CAB-LA where clinically appropriate and medical aid permitting. Public clinics across the George metro offer oral PrEP free of charge.

No aspect of PrEP at NeoHealth involves your employer, family members on shared medical aid accounts, or anyone outside the clinical relationship. PrEP consultations are booked and billed as routine primary care.

Booking at NeoHealth

Whether you are considering PrEP for the first time, want to switch methods, or are transitioning from PEP to ongoing prevention, book a consultation with Dr Chellan at NeoHealth. Within our general practice, he offers full-spectrum HIV care, including prevention, drawing on the Diploma in HIV Management (CMSA).

For urgent PEP enquiries (a possible HIV exposure in the last 72 hours), please call the practice immediately.

Important: This article provides general information on HIV pre-exposure prophylaxis based on current peer-reviewed guidelines, including the SAHCS 2025 PrEP Guideline, the IAS-USA 2024 Recommendations, and the USPSTF 2023 Grade A recommendation. It is intended for educational purposes only. It is not personalised medical advice. Every situation is different. Please seek the advice of Dr Chellan or another qualified healthcare provider for any individual PrEP questions.

Sources and references

• Southern African HIV Clinicians Society. SAHCS PrEP guidelines. Southern African HIV Clinicians Society.
• IAS-USA 2024 Recommendations. Antiretroviral drugs for treatment and prevention of HIV in adults. IAS-USA Clinical Recommendations, 2024 update.
• USPSTF 2023. Preexposure prophylaxis to prevent the acquisition of HIV. US Preventive Services Task Force, Grade A recommendation.
• World Health Organization. Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring. WHO.
• NDoH Knowledge Hub. Standard Treatment Guidelines and Essential Medicines List. South African National Department of Health.
• HIV.gov. HIV treatment and prevention clinical guidelines. US DHHS HIVinfo.
• CDC. Pre-exposure prophylaxis for HIV. Centers for Disease Control and Prevention.
• iPrEx trial. Pre-exposure chemoprophylaxis for HIV prevention in men who have sex with men. Grant et al., NEJM 2010 (PubMed).
• HPTN 083. Cabotegravir for HIV prevention in cisgender men and transgender women. Landovitz et al., NEJM 2021 (PubMed).
• AVAC. PrEP resources and global advocacy. AVAC Global Advocacy for HIV Prevention.

Content on this page is based on these sources and current clinical practice at NeoHealth. It is general health information, not personalised medical advice. Book a consultation for individual assessment.