Pre-Exposure Prophylaxis

Introduction

HIV places a substantial burden on South African communities and the healthcare system. Reducing new infections requires two complementary strategies: diagnosing and treating people living with HIV until they achieve an undetectable viral load, which prevents sexual transmission, and helping HIV-negative people avoid acquiring the virus. Although highly effective HIV treatment is widely recognised, prevention remains underused. Effective PrEP options are now available in both oral and injectable forms. The best option is the one a person chooses and will use consistently—not simply the one a clinician recommends. This article provides practical guidance to support confident PrEP prescribing.

HIV and PrEP in South Africa: Key Statistics

There are 7,6m people living with HIV in SA.
150 000 new cases in 2023. This equates to 410 new cases per day.
45 000 deaths due to AIDS.
The incidence among adults in SA is 17,8%.
- Amongst sex workers – 62%.
- Amongst transgenders – 58%.
- Amongst gay men – 48%.
2,1M SA have made use of PrEP to date.
PrEP can reduce the transmission of HIV by 99% during sexual intercourse and by 74% in injection drug users.
Since 2010 AIDS deaths have decreased by 66% and new infections by 58%

Available HIV-Prevention Strategies

Undetected VL = Untransmissible.
Condoms.
Supply of needles and syringes for drug addicts.
Post Exposure prophylaxis. (PEP)
Oral PrEP.
Long-Acting PrEP.

PrEP should be integrated into routine care across disciplines, including internal medicine, antenatal and postnatal care, youth services, family planning, and sexual and reproductive health clinics.

Who Should Consider PrEP?

Anyone who feels at risk of contracting HIV.
Discordant couples even if viral load (VL) is undetected.
Anyone who has had unprotected vaginal or anal sex in the last six months.
Anyone who has needed PEP on more than one occasion in the last six months.
Anyone who has had treatment for a sexual transmitted disease in the last six months.
Anyone wanting to become pregnant if her partner is HIV positive even if VL is undetected.
Pregnant ladies who are at risk as the chance of contracting HIV during the third trimester and post-partum is twice the normal transmission rate.
Drug users sharing needles.

PrEP Options

Oral PrEP: Tenofovir and emtricitabine (TDF/FTC) are taken once daily.

For people older than 12yrs and more than 30kg.
Accumulates in the genital tract at the site of infection.
Can start and stop as they deem necessary depending on the risk.
44-90% effective.
Safe in pregnancy and breastfeeding.
Follow up every 3 months for HIV test or do home HIV test and visit every 6 months.
Do eGFR if older than 30yrs or any other metabolic risks and review after 3 months and then yearly. It must be more than 50ml/min.
If pregnant do creatinine and not eGFR. Must be less than 80mmol/l.

Dapivirine Vaginal Ring

A NNRT inhibitor.
Placed in the vagina.
Replaced every 28 days.
Low effectivity – 27- 31% (So why use if such a low success rate.)
If 18yrs and over.
For people who have vaginal sex.
Not on state code.
Takes 24hrs to be effective.
Do not remove during menses.
Not approved by the CDC in America.

Long-acting Injectable PrEP

Cabotegravir (CAB-LA)

Integrase strand transfer inhibitor. It thus prevents the virus from integrating the DNA building blocks of the virus into the human DNA.
66% effective and thus more effective than oral PrEP.
For use in younger females, transgenders, MSM and couples.
Stat dose followed by a second injection one month later and then every two months.
Must weigh more than 35kg.
It can be used in pregnancy and breastfeeding.
Do LFT before starting.
Not on state code.

Lencap (Len)

Capsid inhibitor. It binds to the viral protein shell or capsid which surrounds the viral genetic material and disrupts multiple stages such as viral import and particle assembly. *
It is 100% effective, but 96% effective in MSM and transgenders.
The injection is given every six months.
It is on state code and will be rolled out in SA from May 2026 over a 3-year period.
First year in 360 clinics, 24 districts and 6 provinces. It is sponsored by a grant.
Second year – 650-1010 clinics covering 29% of all clinics. Will make use of generic meds and financed by the government.
Third year to all 2464 clinics with 100% cover with generic meds financed by the government.
Two 1,5ml injections given s/c 10cm from umbilicus 10cm apart + 2x 300mg tabs on D1 and D2.
Effective after D3.

Prep options in Developement

Monthly oral PrEP.
Dual prevention pill – Combined PrEP (TDF/FTC) and contraception (Ethinylestradiol and Levonorgestrel).
Dual prevention vaginal ring – Tenofovir / Levonorgestrel.
3 monthly Dapivirine Ring.

HIV Testing before Starting PrEP

PrEP must not be started in a person with HIV, because an incomplete antiretroviral regimen can promote drug resistance. A negative test is reassuring, but clinicians must also consider possible infection during the window period.

Always take into consideration when the last unprotected sexual intercourse was to identify the risk of possible infection. If less than 72hrs postpone and rather use PEP.
Always enquire about signs and symptoms of acute HIV infection.
- Fever.
- Rash.
- Swollen glands.
- Oral thrush.
For oral PrEP and the Dapivirine ring – Self testing is sufficient. If negative start. If positive, follow the 3-test strategy.
Test for HIV after 1 month and then every 3 months.
For CAB-LA it is a different story. Due to the potency of CAB-LA to suppress viral replication and delaying the formation of antibodies to the HIV virus it may cause the rapid tests to test negative despite being infected.
This can result in integrase inhibitor resistance and resistance to the backbone of HIV treatment, Dolutegravir which is also an integrase inhibitor, and this should be avoided at all costs.

The Protocol is thus as follows

Always access the risk of HIV infection by asking about the possibility of being infected in the recent past. Especially last 72hrs.
Are there any symptoms or signs of acute HIV infection?
If so, rather delay the initiation of CAB-LA.
Test, using the 3 Test strategy, using either the 3rd or 4th generation tests to test for HIV.

i. If negative one can commence PrEP.
ii. If positive test with a second test and if positive do a third test and if positive they are infected and should be treated and not receive PrEP. (3-test)
iii. If tests positive and second test negative, the result is discordant and one should do an ELISA, VL or NAAT.
iv. If positive and second test also positive but third negative it is again a discordant result and should be managed with ELIZA, VL or NAAT.

While on CAB-LA test every 2 months when receiving the injection and using 4th generation tests.

Follow-up After Starting PrEP

At Every Visit

Do HIV test with every visit.
Do STD screen.
Check if Hep B Screen was done.
Do pregnancy test.

Oral PrEP

One month to check if any problems with PrEP.
3months and supply 3 test kits to check HIV status monthly.
Do eGFR.
6 months with 6 test kits.

CAB-LA

Stat one month.
2 months and every 2months.

Lenacapavir

Do LFT.
One month.
6 months injection at any site and test.

Eight-step Follow-up Checklist

Ask how the person is managing on PrEP.
Confirm HIV status using the recommended testing algorithm.
Provide counselling on PrEP choice and general HIV prevention.
Confirm that the person is satisfied with the chosen method or discuss switching.
Complete the required safety monitoring.
Offer integrated sexual and reproductive healthcare, such as antenatal care, family planning, or school health services.
Provide the selected PrEP method.
Schedule the next follow-up visit.

Time to Protection and Switching Between PrEP Methods

Type of PrEP	Effective after
Oral PrEP	7 days
DVR	24 hrs
CAB-LA	7 days
LEN	3 days

People may choose to change from one PrEP method to another. The lead-in periods below show when protection is expected after starting or switching methods.

Present drug	Switch to	When protected
Oral PrEP	Dapivirine Ring	24hrs for vaginal sex. 7 days for other forms.
Oral	CAB-LA	7days
Oral	LEN	3 days
CAB-LA	Any other form	Immediately if within 8 weeks of last injection. After 8 weeks as for each individual drug.
Lenacapavir	Any other drug	If within 26 weeks after last injection it is immediate. After 28 weeks as for each individual drug.

Managing Missed Doses

Medication	Missed dose	What to do	When safe
Oral Pr-EP	1 dose	Take ASAP and continue	Safe
	2 doses	Restart	7 days
DVR	<24hrs	Restart	24hrs
CAB-LA	<4 weeks	Continue	Safe
	>4 weeks	Restart 1,2 and 2 monthly	7 days
LEN	<28 weeks	Continue	Safe
	>28 weeks	Restart 2×1,5ml injections on D1, 2x 300mg tabs D1 and D2.	Third day

Transitioning Between PrEP and PEP

When PrEP doses have been missed and a potential HIV exposure occurred within the past 72 hours, prescribe a 28-day course of PEP according to the applicable protocol.
After completing PEP, a person who remains at risk may transition directly to an appropriate PrEP method.

Before starting PEP do the following:

HIV test rapid and 4th generation Eliza.
STD – RPR, Hep B and C, NG and Chlamydia.
Pregnancy test
Creatinine.

Follow up at 6 weeks with HIV test, Pregnancy test and Hep C.
Follow up at 12 weeks with HIV test, Pregnancy test and Hep B.

Transition to PrEP immediately after 28 days of PEP.

Oral PrEP – immediately safe. Do creatinine.
DVR – after 24hrs.
CAB-LA – after 7 days and do AST and ALT.
Lenacapavir – on D3.

PrEP During Pregnancy and Breastfeeding

The chance of contracting HIV is higher in pregnancy and in the post-partum period:

Early pregnancy – twice the risk.
Late pregnancy – 3 x the risk.
Post-Partum – 4 x the risk.
Average for the period early pregnancy to post-partum is 2,8x the risk.

In South Africa:

180 000 cases acquired HIV during pregnancy.
16 000 were not offered PrEP.
14 000 did not use their ARV’s.
7 400 were on treatment but not suppressed.

Drug	Safe in Pregnancy and Breastfeeding	Precautions
Oral PrEP	Yes	Creatinine <80
DVR	No	Not safe in pregnancy but during post-partum and breastfeeding it is safe.
Lenacapavir	Yes	LFT- AST and ALT.
CAB-LA	Yes

Side effects of oral PrEP and pregnancy, with nausea and vomiting overlap. Thus, best taken at night and not with iron supplements.

Summary

Comprehensive HIV care includes more than treating people who have already been diagnosed. It also requires routine testing, counselling on safer sex, treatment to an undetectable viral load, and effective prevention for people at ongoing risk. A growing range of oral, vaginal, and long-acting PrEP options allows care to be tailored to individual needs. Clinicians should ensure that people know these choices are available and support them in selecting a method they are willing and able to use consistently.

Resources

SA HIV Society PrEP Course.
South African HIV Clinicians Society Guideline on PrEP to prevent HIV.
Pippa Macdonald, Gonasagrie Nair, Camilla Wattrus, Saiqa Mullick, Melanie Pleaner, Elzette Rousseau, Hasina Subedar, Dvora Joseph-Davey, Johan Hugo, Sinead Delany-Moretlwe, Linda-Gail Bekker.
Received: 18 Feb. 2025; Accepted: 19 Feb. 2025; Published: 11 Apr. 2025.
Pubmed – National library of medicine.*