Senior Consultant, Infectious Diseases, Fortis Memorial Research Institute, Gurgaon
Part 4 of 9 in Tuberculosis & HIV - An Insight
Pre-Exposure Prophylaxis for HIV: Who Qualifies and How Well It Works
September 6, 2026
A young couple is getting married. One partner is HIV-positive and on antiretroviral therapy; the other is negative. Their question is a common one: can we have a normal married life, and is there something the negative partner can take to stay that way? Pre-exposure prophylaxis, PrEP, is the direct answer, and how well it works depends almost entirely on how it's used.
Who PrEP Is For
PrEP is prescribed to HIV-negative adults at higher risk of acquiring HIV: men who have sex with men, heterosexual women and men with a positive or unknown-status partner, and people who inject drugs. In a discordant couple, where one partner is positive and virally suppressed on treatment, the principle of U=U, undetectable equals untransmissible, already provides strong protection, and PrEP for the negative partner adds a second layer during the period before that suppression is achieved and confirmed.
How Well It Actually Works
Efficacy ranges from 75 to 99 percent, and the deciding factor is adherence, not the drug itself. Above 90 percent adherence, PrEP cuts the risk of acquiring HIV by roughly 73 percent on self-reported use and up to 92 percent with near-perfect adherence. Daily oral PrEP also takes different lengths of time to reach protective drug levels depending on the route of exposure: about a week for anal sex, roughly three weeks for vaginal sex, and 21 days for people whose exposure is through injecting drug use, so PrEP is not something that protects from the first dose regardless of how it is being used.
Daily Pills, Two-Drug Regimens, and On-Demand Dosing
The two approved daily regimens combine emtricitabine with either tenofovir disoproxil fumarate or tenofovir alafenamide. They perform similarly, with the same side-effect trade-off seen in HIV treatment itself: the TDF-based option carries kidney and bone risk, while the TAF-based option is associated with lipid changes and weight gain instead. For people with infrequent exposure, fewer than two occasions a week, an on-demand regimen built around four pills timed to the specific exposure is also available, though it should not be treated as more than 90 percent effective on every occasion the way daily dosing is, since starting it very early and very frequently around isolated exposures raises the risk of drug resistance. Condoms remain the recommended anchor alongside on-demand dosing, not a replacement for it.
A Twice-Yearly Injection on the Horizon
Lenacapavir, a capsid inhibitor that blocks HIV replication at two separate points in its life cycle, was tested as a PrEP option in a phase three trial published last year in the New England Journal of Medicine, enrolling more than 5,000 sexually active adolescent girls and young women in South Africa and Uganda who were not already using PrEP. A twice-yearly subcutaneous injection reduced HIV incidence by close to 100 percent overall, with a subset analysis at 93 percent, against oral PrEP comparator arms, with injection-site pain as essentially the only side effect reported. A single injection maintains protective drug levels for around 26 weeks.
This guide is based on a live Jivo Masterclass: Dr. Neha Rastogi Panda taught doctors across Africa on March 30, 2025.
FROM THE LIVE Q&A
Dr. Rabio
At what stage can we diagnose opportunistic infections, and how do we diagnose them?
Dr. Neha Rastogi Panda
Opportunistic infections can be diagnosed at any stage; the WHO staging system, grade one through four, is built around exactly this, using the infection profile and CD4 level together. Oral thrush, for instance, usually appears at stage two, while reactive generalised lymphadenopathy sits at stage one. Sometimes the opportunistic infection is itself the first clue to an undiagnosed HIV infection, tuberculosis being the clearest example: finding it usually puts the patient at WHO stage three, and a very low viral load and CD4 count below 200 to 250 lets you further risk-stratify from there. Diagnosis runs on three legs: the clinical symptoms and signs, which organ is involved, and targeted sampling, such as testing sputum by GeneXpert for suspected pulmonary tuberculosis, or testing CSF, or serum cryptococcal antigen when CSF isn't accessible, for cryptococcal meningitis.
Book a Consultation with Dr. Neha Rastogi Panda
Book on WhatsAppOr message us on WhatsApp: +91 98182 98669
Frequently Asked Questions
What are the early signs of HIV?▼
The early signs, known as acute HIV syndrome, look like a flu. Most patients who are symptomatic present with intermittent fever for two to three months, fatigue or weakness, weight loss, loss of appetite, cough, cold, sore throat, more frequent minor illnesses than usual, and loose motions or diarrhoea. This symptom complex over the first month or two is what we call acute HIV syndrome.
Why don't we use the urine LAM test and stool test for all patients?▼
The urine lipoarabinomannan (LAM) test is reserved for tuberculosis diagnosis, and it has only been validated for patients with a CD4 count below 100. Below that threshold, a high tuberculosis bacterial burden allows the antigen to wash out into the urine; above it, the test loses sensitivity and specificity, so extrapolating it to every patient isn't supported. On stool testing for other opportunistic infections, a high viral load before treatment changes the normal gut flora, so a stool sample will often show excess normal flora and candida, which makes interpreting it for treatment decisions difficult specifically in HIV patients.
Are there any antiretrovirals that can have prolonged action for up to three or six months?▼
Yes. Cabotegravir, a longer-acting integrase inhibitor, combined with rilpivirine from the non-nucleoside reverse transcriptase inhibitor family, was studied in the TANGO trial and showed viral suppression sustained for close to three months from a single dose. Their half-life runs to about 24 to 26 weeks, so the combination is given as one intramuscular or subcutaneous injection every three months for patients who are already stable on oral therapy, as maintenance rather than as a starting regimen.
At what stage can we diagnose opportunistic infections, and how do we diagnose them?▼
Opportunistic infections can be diagnosed at any stage; the WHO staging system, grade one through four, is built around exactly this, using the infection profile and CD4 level together. Oral thrush, for instance, usually appears at stage two, while reactive generalised lymphadenopathy sits at stage one. Sometimes the opportunistic infection is itself the first clue to an undiagnosed HIV infection, tuberculosis being the clearest example: finding it usually puts the patient at WHO stage three, and a very low viral load and CD4 count below 200 to 250 lets you further risk-stratify from there. Diagnosis runs on three legs: the clinical symptoms and signs, which organ is involved, and targeted sampling, such as testing sputum by GeneXpert for suspected pulmonary tuberculosis, or testing CSF, or serum cryptococcal antigen when CSF isn't accessible, for cryptococcal meningitis.
In This Series: Tuberculosis & HIV - An Insight
- 1.Tuberculosis and HIV
- 2.How HIV Is Diagnosed: Getting the Testing Window Right
- 3.Starting Antiretroviral Therapy: Building the Regimen Around the Patient
- 4.Pre-Exposure Prophylaxis for HIV: Who Qualifies and How Well It Works
- 5.Post-Exposure Prophylaxis: Acting Within 72 Hours of a Possible HIV Exposure
- 6.Tuberculosis and HIV Co-Infection: Why the Two Diseases Compound Each Other
- 7.Preventing Mother-to-Child Transmission of HIV
- 8.When HIV Therapy Appears to Fail: Telling Adherence Problems From Real Failure
- 9.Long-Acting HIV Therapy and the Path Toward a Cure