HIV Prevention: PrEP, PEP and Mother-to-Child Transmission

HIV prevention now rests on three tools. Pre-exposure prophylaxis (PrEP) protects HIV-negative people at high risk and, taken with good adherence, reduces infection risk by 75% to 99%. Post-exposure prophylaxis (PEP) should start as soon as possible after an exposure, and within 72 hours, for 28 days. Antiretroviral therapy in pregnancy, with infant nevirapine prophylaxis, makes mother-to-child transmission largely preventable.

Dr. Neha Rastogi, Senior Consultant Infectious Diseases, Fortis Memorial Research Institute, Gurgaon, India, framed prevention in her masterclass as a matter of timing: "it's not only about reacting, it is also sometimes about action in the right way and at the right time." She framed the subject around the situations that bring people to a clinic: a woman about to marry a man with HIV, young people who want protection around an anticipated encounter, a resident with a needlestick injury and a mother who learns her status in the first trimester. This article follows those situations in turn. Diagnosis and the testing window, which underpin every decision here, are covered in the complete guide to tuberculosis and HIV.

HIV prevention in a serodiscordant couple

A serodiscordant couple is one in which one partner has HIV and the other does not. Dr. Rastogi Panda's case was an HIV-negative young woman about to marry an HIV-positive man who was already on antiretroviral therapy. She came with her own concerns and asked whether she was eligible for PrEP.

She is. PrEP means that a person in close sexual contact with someone who has HIV takes antiretroviral medicine in advance to reduce the risk of acquiring the infection. It is prescribed for HIV-negative adults at higher risk of acquiring HIV. Her partner's own treatment matters just as much: once his viral load is undetectable, he does not transmit HIV through sex, the principle known as U=U (undetectable equals untransmittable).

Who should be offered PrEP?

PrEP is for HIV-negative people at substantial risk of acquiring HIV from known or unknown partners. Dr. Rastogi Panda identified four groups who present to the clinic:

• Men who have sex with men
• Heterosexual women
• Heterosexual men
• People who inject drugs

The HIV-negative partner in a serodiscordant couple, as in her case, sits squarely within this population.

How effective is PrEP?

PrEP is highly effective, and its effectiveness depends almost entirely on adherence. Dr. Rastogi Panda put the reduction in risk at between 75% and 99%, depending on how consistently it is taken and in what circumstances. When adherence exceeds 90%, the reduction in HIV acquisition is substantial. Adherence, not the drug, is the deciding variable.

How long does PrEP take to work?

Daily oral PrEP does not protect from the first pill: protective drug levels take about 7 days to build up for receptive anal sex and about 21 days for receptive vaginal sex and injecting drug use. Dr. Rastogi Panda gave the intervals:

In practice, protective levels are reached within one to three weeks of starting daily PrEP, depending on the route of exposure.

On-demand PrEP: the 2-1-1 schedule

On-demand, or event-driven, PrEP is an option for people who have sex infrequently, fewer than two times a week, or who can anticipate a sexual encounter. Dr. Rastogi Panda described the patients it suits: young people who expect to meet a new partner. A person who arrives after an unplanned encounter has already been exposed and needs post-exposure prophylaxis, not PrEP. The schedule uses four pills taken at three time points: two pills 2 to 24 hours before sex, one pill 24 hours after the first dose and one pill 48 hours after the first dose. WHO recommends this schedule for men who have sex with men; it is not recommended for women.

She attached a clear caution. Repeated use does not guarantee more than 90% efficacy every time. Because the drugs act for a short period, very frequent, last-minute use raises the risk of drug resistance. Guidelines identify taking PrEP while already infected, without knowing it, as the main route to PrEP-related resistance, which is why HIV testing before and during PrEP is standard. Condoms remain the standard protective measure, and on-demand PrEP is best seen as an additional option for the patient who asks for it.

PrEP drugs: TDF or TAF with emtricitabine

Two oral combinations are approved for PrEP:

• Tenofovir disoproxil fumarate with emtricitabine (TDF/FTC)
• Tenofovir alafenamide with emtricitabine (TAF/FTC)

Their efficacy is broadly matched, and they differ in side effects. TDF can reduce bone density and affect kidney function. TAF carries far less of that kidney and bone toxicity, but it causes some lipid disturbance and can contribute to weight gain and a higher body mass index. In the United States, TAF/FTC is licensed for PrEP only for people at risk through sex other than receptive vaginal sex; for people at risk through receptive vaginal sex, TDF/FTC remains the oral option.

Twice-yearly lenacapavir injection for HIV prevention

The most important recent advance in prevention is lenacapavir, which Dr. Rastogi Panda called a path-breaking discovery. Lenacapavir is a capsid inhibitor: it disrupts the protein shell that encloses the virus's genetic material, acting at both the early and late stages of HIV replication. In a long-acting formulation injected under the skin, it is released slowly and maintains protective drug levels for about 26 weeks, so a single injection covers six months.

The evidence comes from a phase 3 trial published in the New England Journal of Medicine in 2024. It enrolled more than 5,000 sexually active adolescent girls and young women in South Africa and Uganda who were not using PrEP, and compared twice-yearly lenacapavir with daily oral PrEP. No HIV infections occurred among the women who received lenacapavir. The main side effect was injection-site pain, which Dr. Rastogi Panda described as mild and easily managed with simple painkillers.

The implication, in Dr. Rastogi Panda's words, is that with two injections a year a person can lead a full life with their partner, physically and mentally, though monitoring remains essential.

Post-exposure prophylaxis (PEP) after a needlestick injury

PEP is the emergency course of antiretroviral drugs taken after a possible exposure to HIV. Dr. Rastogi Panda's case is one many doctors have lived through. A young resident was taking blood from a patient on antiretroviral therapy for six years, admitted to the ward with Pneumocystis pneumonia (PCP), and sustained a needlestick injury. The resident's immediate fears were whether infection had occurred, what it would mean and what to do next.

Which exposures carry the highest risk?

The most common route of HIV transmission is not the highest-risk route. Sexual intercourse accounts for most infections, but the risk per exposure is highest with transfusion of infected blood or blood products, above 90%. Without treatment, transmission from mother to child occurs in about 15% to 45% of pregnancies, while the risk after a needlestick injury from an HIV-positive source is about 0.3% and after a single sexual exposure generally below 1.5%. Dr. Rastogi Panda described the gap between "most common" and "highest risk" as a widespread misconception.

The fluids considered high risk are:

• Blood
• Semen
• Vaginal secretions
• Breast milk
• Cerebrospinal fluid and certain other body fluids

The 72-hour window

PEP should start as soon as possible and within 72 hours of exposure, because the virus has an incubation and replication period that the drugs must interrupt. Dr. Rastogi Panda noted that in the rarest of circumstances, when people present late, her team has offered PEP up to day five. International guidelines from WHO and the US CDC do not recommend starting PEP more than 72 hours after an exposure.

Why PEP should never wait for an HIV test result

People often ask whether they should wait for an HIV test result before starting PEP. They should not. A test taken on the day of the exposure reflects only infection acquired at least two to four weeks earlier, the minimum time for HIV to become detectable, so it says nothing about the exposure that has just happened. Testing for that exposure must wait two to four weeks. The decision to start PEP rests on the nature of the exposure and the status of the source patient. If the source is known to be HIV positive, PEP should be started without hesitation.

The PEP regimen

PEP uses the same three-drug structure as standard antiretroviral therapy:

1. A tenofovir backbone, either TDF or TAF
2. Emtricitabine
3. An integrase inhibitor, most commonly dolutegravir in Asian and African settings

The course lasts 28 days from the start, after which the person returns for antibody testing.

Preventing mother-to-child transmission of HIV

Mother-to-child transmission of HIV is prevented by antiretroviral therapy in pregnancy, nevirapine prophylaxis for the infant, careful feeding decisions and virus-based testing of the baby. The language itself has changed. The older term, prevention of parent-to-child transmission (PPTCT), has given way to the elimination of mother-to-child transmission (EMTCT). The shift from prevention to elimination reflects how effective the tools have become. Dr. Rastogi Panda's case, which sits at the overlap with obstetrics and gynaecology, was a woman who learns from first-trimester screening that she has HIV, and the four questions that follow: which regimen, whether the baby needs prophylaxis at birth, whether she can breastfeed, and how to follow the baby up.

Antiretroviral therapy in pregnancy

A pregnant woman with HIV presents in one of two ways: diagnosed at the start of pregnancy and not yet on treatment, or already on ART when she conceives. In both cases the regimen is essentially the same standard therapy. A mother who takes effective ART throughout pregnancy and achieves good viral suppression greatly reduces the risk of transmission to the baby, and she can continue the same drugs.

Infant prophylaxis

An exposed infant should receive nevirapine syrup as prophylaxis, for six weeks as standard. Higher-risk infants, such as those whose mothers have a high or unknown viral load, receive extended prophylaxis for up to 12 weeks.

Can a mother with HIV breastfeed?

In Dr. Rastogi Panda's practice, a mother whose viral load is suppressed can breastfeed; if her viral load is above 1,000 copies, replacement feeding is preferred. There is no single consensus on breastfeeding, and she reasons from first principles: breast milk is one of the high-risk fluids. WHO advises that where national programmes promote breastfeeding, mothers living with HIV breastfeed while taking ART with support for adherence.

Testing the infant

Antibody tests are unreliable in young infants, because a baby carries the mother's antibodies for months after birth. Infant diagnosis therefore relies on detecting the virus itself:

• From 6 weeks to 6 months of age: a dried blood spot is tested by HIV PCR at six weeks, followed by repeat testing.
• After 6 months of age: the three antibody tests used in adult diagnosis are performed, and a reactive result is confirmed by HIV PCR.

Effective maternal therapy, infant prophylaxis and careful feeding decisions together make transmission from mother to child rare.

HIV prevention and treatment are one strategy

Each of these tools draws on the same drugs and the same principles as treatment. Suppressing the viral load in a person with HIV protects their partner; antiretroviral drugs taken before or after an exposure protect a person without HIV; and therapy in pregnancy protects the child. How those regimens are chosen, how failure is recognised and how tuberculosis complicates the picture are set out in HIV treatment: ART regimens, failure and TB co-infection. The questions doctors raised during the session are answered in the Live Discussion.