HIV and AIDS — Viva

Long Case Viva Defence

Candidate's opening statement (model answer)

"Mr James Wiremu is a 38-year-old man presenting with a new diagnosis of HIV infection with a CD4 count of 140 cells per microlitre and a viral load of 180,000 copies per millilitre. He was diagnosed with pulmonary tuberculosis three weeks ago and is on rifampicin-based quadruple therapy. He is chronically infected with hepatitis B (HBsAg positive, HBeAg negative, HBV DNA 2 million IU per millilitre). His creatinine is 190 micromol per litre with an eGFR of 35, attributed to HIV-associated nephropathy. He has a history of depression and intermittent methamphetamine injection. ^[1]

His main problems are:

1. Advanced HIV with a CD4 of 140 — requiring immediate ART under the Treat All policy, with careful sequencing against active TB.
2. Active pulmonary tuberculosis on rifampicin-based therapy — the dominant timing and drug-interaction challenge.
3. Chronic hepatitis B co-infection with high viral load — his ART must include dual anti-HBV agents.
4. Moderate renal impairment (eGFR 35) — requiring TAF instead of TDF and avoidance of nephrotoxins.
5. Psychosocial complexity — depression and injection drug use, both of which threaten adherence. ^[1]

My management plan is: first, a baseline resistance test and confirmatory workup; second, start ART within 2 weeks of TB therapy initiation using tenofovir alafenamide plus lamivudine plus dolutegravir 50 mg twice daily (dose-doubled for the rifampicin interaction), reverting to once-daily dolutegravir after rifampicin completes; third, co-trimoxazole prophylaxis for PCP and toxoplasmosis at CD4 140; fourth, renal function monitoring and avoidance of nephrotoxins; fifth, integrated mental health and addiction support; and sixth, the U equals U counselling framework for him and his partner. The target is an undetectable viral load within 12 to 24 weeks, CD4 recovery above 200 for prophylaxis discontinuation, and sustained lifelong adherence." ^[1]

Examiner probing questions and model answers

Q1: "Why dolutegravir and not efavirenz for this patient?" ^[1]

"Dolutegravir is superior to efavirenz for several reasons that are all relevant to this patient. First, the SINGLE trial demonstrated dolutegravir plus abacavir-lamivudine was superior to efavirenz-tenofovir-FTC at week 48, with 88 per cent versus 81 per cent viral suppression, driven primarily by fewer discontinuations for adverse events ^[6]. Second, dolutegravir has a high genetic barrier to resistance — no treatment-emergent resistance mutations were observed in the SINGLE trial — which is critical for a patient with adherence challenges from injection drug use. Third, efavirenz has significant neuropsychiatric side effects including depression, vivid dreams, anxiety and suicidality, which would compound his pre-existing depression. Fourth, the initial concern about dolutegravir and neural tube defects from the Tsepamo study ^[9] has been resolved by expanded surveillance — WHO now recommends dolutegravir-based regimens for all adults and adolescents including women of childbearing potential. Efavirenz remains a viable alternative in resource-limited settings and is rifampicin-compatible without dose adjustment, but dolutegravir with dose-doubling is the better choice for this patient."

Q2: "How do you manage the interaction between dolutegravir and rifampicin?" ^[1]

"Rifampicin is a potent inducer of hepatic CYP3A4 and UGT1A1 enzymes, which reduces dolutegravir plasma concentrations by approximately 50 per cent. If I prescribed standard-dose dolutegravir (50 mg once daily) alongside rifampicin, the reduced drug exposure would risk subtherapeutic levels, virological failure, and the emergence of INSTI resistance. The established compensatory strategy, endorsed by WHO and DHHS guidelines, is to double the dolutegravir dose to 50 mg twice daily for the entire duration of rifampicin co-administration. Once the rifampicin course is completed — typically after the 6-month continuation phase of TB therapy — the dolutegravir dose reverts to 50 mg once daily. I would monitor the viral load at 2 to 8 weeks after ART initiation to confirm the early response, and continue twice-daily dolutegravir until rifampicin is stopped." ^[1]

Q3: "When would you start ART relative to his TB treatment, and what is the evidence?" ^[1]

"The ART-TB timing question is governed by two competing risks: the benefit of early immune recovery versus the risk of TB-associated IRIS. The pivotal evidence comes from three trials. The SAPiT trial, conducted in South Africa, showed that starting ART during TB treatment (within 4 weeks for patients with CD4 below 50, within 8 weeks for higher CD4) reduced mortality and AIDS progression compared with starting ART only after TB treatment was complete. The CAMELIA trial, conducted in Cambodia, confirmed that very early ART (within 2 weeks of TB therapy) reduced mortality in patients with CD4 below 200. The timing was further refined by the ACTG A5221 (STRIDE) trial. ^[1]

For this patient with CD4 140, I would start ART within 2 weeks of TB therapy initiation. The benefit of early immune recovery outweighs the IRIS risk at this CD4 level. I would counsel him explicitly about TB-IRIS — paradoxical fever, worsening lymphadenopathy, worsening infiltrates or effusions occurring within the first 4 to 8 weeks of ART — and reassure him that this is an inflammatory response to recovering immunity, not treatment failure or drug resistance. ART is continued through IRIS. Severe IRIS, particularly with respiratory compromise, is managed with corticosteroids: prednisolone 1.5 mg per kg per day for 2 weeks, then tapering over 4 weeks, based on the randomised trial by Meintjes et al." ^[1]

Q4: "What about the hepatitis B co-infection — what are the specific risks?" ^[1]

"Chronic hepatitis B co-infection affects approximately 5 to 10 per cent of people living with HIV and accelerates liver fibrosis, cirrhosis and hepatocellular carcinoma. The critical management principle is that his ART regimen must include two agents active against both HIV and HBV — in this case tenofovir (TAF) and lamivudine — because single-agent anti-HBV therapy in the context of HIV drives HBV resistance, and stopping anti-HBV coverage without an alternative agent can precipitate severe HBV flares, hepatic decompensation and death. I would never stop or change his tenofovir or lamivudine without ensuring continued anti-HBV coverage. ^[1]

I would monitor his HBV DNA, liver function tests and HBV serology every 3 to 6 months, looking for HBV DNA suppression (the goal is undetectable HBV DNA), HBeAg seroconversion if he is HBeAg positive (he is HBeAg negative), and HBsAg loss (rare but the ultimate goal). He requires hepatocellular carcinoma surveillance with liver ultrasound and serum AFP every 6 months, given his HBV co-infection. If his HBV DNA does not suppress on tenofovir plus lamivudine, I would involve hepatology and consider adding entecavir (which has anti-HBV but not anti-HIV activity). I would also ensure he is vaccinated against hepatitis A if seronegative." ^[1]

Q5: "He asks whether he will transmit HIV to his partner. How do you answer?" ^[1]

"I would answer with the evidence-based and empowering message of U equals U: once his viral load is undetectable on ART (below 50 copies per millilitre), the risk of sexual transmission of HIV is effectively zero. This is established by the PARTNER study (serodifferent couples, predominantly heterosexual and some MSM) ^[2] and PARTNER2 (exclusively gay male serodifferent couples) ^[3], which together recorded zero phylogenetically linked HIV transmissions across over 126,000 acts of condomless sex among couples where the HIV-positive partner was on suppressive ART. This evidence, combined with the HPTN 052 trial showing a 96 per cent reduction in transmission with early ART ^[1], established the consensus endorsed by WHO, CDC, BHIVA and ASHM: Undetectable equals Untransmittable.

I would explain that achieving and maintaining an undetectable viral load requires sustained ART adherence, and that it typically takes 12 to 24 weeks to reach undetectable from a starting viral load of 180,000. Until his viral load is confirmed undetectable, I would advise consistent condom use. For his partner, I would offer HIV testing (if she has not been tested), and if she is HIV-negative and at ongoing risk, I would discuss PrEP — daily oral tenofovir plus emtricitabine, which the iPrEx trial showed reduces HIV acquisition by 44 per cent overall and over 90 per cent in those with detectable drug levels ^[4]. U equals U is both a clinical and a psychosocial message — it removes stigma, supports adherence, and is the foundation of treatment as prevention."

Q6: "What is the role of isoniazid preventive therapy in HIV?" ^[1]

"Isoniazid preventive therapy (IPT) reduces the risk of TB disease in people living with HIV by treating latent TB infection before it progresses. The TEMPRANO trial, conducted in Cote d'Ivoire, demonstrated that 6 months of IPT reduced the risk of severe illness or death from HIV by 44 per cent in the context of early ART ^[5]. For this patient, IPT is not applicable because he already has active TB — IPT is for latent infection only, and giving IPT to a patient with active TB risks monotherapy resistance. However, IPT is a critical intervention for his HIV-positive contacts and for future TB prevention once his active TB is treated. In TB-endemic regions including parts of the ANZ tropical region and the Asia-Pacific, IPT after excluding active TB (with symptom screening and chest X-ray) is recommended by WHO alongside ART. The duration is typically 6 months of isoniazid, or shorter rifamycin-based regimens (3 months of rifapentine plus isoniazid) in some settings."

Q7: "What is the significance of the Tsepamo study and how has it changed practice?" ^[1]

"The Tsepamo study in Botswana initially raised concern in 2018 that dolutegravir at conception was associated with neural tube defects, with a preliminary prevalence of 0.94 per cent ^[9]. This caused global guideline caution and led many countries to avoid dolutegravir in women of childbearing potential. However, with expanded surveillance and more data, the estimated prevalence fell to 0.10 to 0.30 per cent — a small or non-significant excess over the background rate. By 2022, updated Tsepamo data found no statistically significant association between dolutegravir and neural tube defects. WHO now recommends dolutegravir-based regimens for all adults and adolescents, including women of childbearing potential, because the substantial benefits (high efficacy, high barrier to resistance, fewer interactions than efavirenz) far outweigh the now-reassuring safety signal. Good practice remains to counsel women of childbearing potential about the data and to offer alternative regimens if they prefer, but dolutegravir is no longer avoided in this group."