HIV 2022: An update

HIV 2022:

An update

Watch the replay here: https://event.webinarjam.com/ go/replay/400/ox64xu33synh28a0

Dr K.D. Mahomed

(HIV Clinician) MBChB (Natal), DCH, DA, DIP HIV (SA)

This enlightening and important webinar was presented by HIV clinician Dr Kay Mahomed, of Netcare Garden City. This webinar hosted by Medical Chronicle and sponsored by Johnson&Johnson. The following article is based on Dr Mahomed’s presentation.

ANTIRETROVIRAL TREATMENT

(ART) is used for the treatment and prevention of HIV. In terms of the treatment of HIV, this is done with the aim of maximal suppression of viral replication (undetectable viral load [VL]), and the restoration of immune function (CD4 cell count). ART is life long and 100% adherence is essential. New drugs have lesser side effect and toxicity profile, and there is a good selection of drugs to fit into a patient’s profile, offering fixed-dose combination and daily dosing. For the prevention of HIV there is post-exposure prophylaxis (PEP) and preexposure prophylaxis (PrEP).

ANTIRETROVIRALS (ARVs)

Therapy includes: • Nucleoside reverse transcriptase inhibitors (NRTI) • Non-nucleoside reverse transcriptase inhibitors (NNRTI) • Protease inhibitors (PI) • Integrase inhibitors • Fusion inhibitors • Entry inhibitors.

THERAPEUTIC STRATEGIES

Always use three agents: • 2 NRTIs +1 NNRTI • 2NRTIs+1PI+low dose RTV • 2 NRTIs + 1 Integrase Inhibitor • 2 NRTIs + 1 Integrase Inhibitor + 1 PI + low dose RTV • 1 NNRTIs + 1 Integrase Inhibitor + 1 PI + low dose RTV. Triple therapy has a pronounced and prolonged Impact on VL. You can do a one-drug switch for side effects. You need to do a regimen change if there is no viral suppression.

NRTIs include: • Stavudine (d4T). Use Tenofovir (TDF) 3/12 if renal failure/ anaemia • Didanosine – no longer used • TDF. Tenofovir alafenamide (TAF) 25mg daily, has less renal and bone density side effects) • Zidovudine (AZT), if TDF contraindicated, no anaemia/ bone marrow failure • Abacavir (ABC).

If TDF contraindicated, watch VL: • Lamivudine (3TC) • Emtricitabine (FTC). These are the backbone of highly active antiretroviral therapy (HAART) drugs with high and low barriers to resistance. NRTIs inhibit viral reverse transcriptase enzyme, by incorporating into the newly developed chain of viral DNA competitively as building blocks. NNRTIs • Nevirapine (NVP) – no longer used • Efavirenz (EFV) (be aware of breast abnormalities, hepatoxic and

CNS symptoms) • Rilpivirine. Use cautiously in TB, monitor

VL and be aware of ulcers.

These are part of the ‘first line’ of HAART cross-resistance ‘low genetic barrier’ to resistance (resistance develops rapidly). NNRTIs inhibit the viral reverse transcriptase enzyme: • Etravirine • Doravirine.

INTEGRASE INHIBITORS

Raltegravir (RTG): • Fewer CNS adverse events than EFV • Drops VL quicker • Lower lipid levels • PEP • Has a low barrier to resistance. Dolutegravir (DTG): • 50mg once daily • Double dose with RIF/EFV • Emtricitabine (FTC) with ABC/3TC requires human leukocyte antigen (HLA) testing • Take care with antacids • Increases metformin levels • Shift workers • DTG has a high barrier to resistance.

NEW REGIMEN OPTIONS Regimen 1: Strengths

TEE: Previously used extensively. Can be used with TB

TER: Fewer neurological side effects. Once daily dosing. Excellent for shift workers. No interaction with hormonal contraception. No teratogenicity. Keeping options open.

TLD: Rapid viral suppression high genetic barrier to resistance. Does not need initiation. Once daily dosing (AM). Excellent for shift workers. No food restriction. Can be used with TB (double dose DTG). No interaction with hormonal contraception). Use in PEP.

Regimen 1: Caution

TEE: Neuro-psychiatric s/e (pyschosis, bad dreams, insomnia, fatigue, drowsiness, dizziness and/or memory loss). Hepatoxic Gynaecomastia. Drug rash. Cannot use in shift workers. TER: VL < 100,000Cannot be used with TB Ulcer drugs TLD: Weight gain Insomnia and agitation. Diabetes (increases metformin levels).

Regimen 2: Strengths

LPV/r: Can be used with RIF-based TB tx but must be double-dosed. ATV/R: Co-combination of ATV 300 + Norvir100. Single tablet taken once a day, convenient dosing (previously 2/3 tablets) Better tolerated, adherence advantage. Low GIT side effects Better metabolic profile Dyslipidaemia significantly reduced two tablets once a day (Truvada/ Tarito, Dumiva/ Tarito). Can be taken at any time of the day. Cost and convenience.

DRV/r: High genetic barrier to resistance. Low GIT side effects. Can be used second and third line. No jaundice. Stanford scoring.

Regimen 2: Caution

LPV/r: Pill size B.D dosing. Greater GIT side effects (diarrhoea, nausea, vomiting, abdominal pain, bloating). Worse metabolic profile. No dyslipidaemia. ATV/r: Unconjugated hyper-bilirubinaemia, resulting in visible jaundice in a minority of patients. This does not indicate hepatic toxicity and is not a reason to discontinue the drug unless it is a worry to the patient for cosmetic reasons (reversible upon discontinuation). Cannot be used with RIF-based TB tx. DRV/r: Cost 400 / 100, 800 / 100, 600 / 100 B.D Cannot use with RIF-based TB treatment.

PREVENTION

PEP is used in cases of: • Exposure • Effective within 72 hours • Rapid • TLD can be given for one month and then retest.

PrEP is for: • HIV-negative patients who want to remain

HIV negative • Rapid, creatinine, HepB, Elisa tests done, then can be put onto emtricitabine/

tenofovir • Can cycle on and off.

TAKE NOTE

1. Creatinine monitoring is important in all patients we see. This is because TDF has an effect on the kidneys.

2. VL monitoring is crucial. If the VL is undetectable, you are ensuring that the partner continues to remain negative, and babies are born HIV free.

3. TB is endemic in SA. Need to symptom screen for TB all the time. Ask patients about symptoms every time you see them – loss of appetite, loss of weight, night sweats, cough.

4. You can prevent TB in patients by giving them Isoniazid preventive therapy (IPT).

5. Be aware of the phenomenon of immune reconstitution inflammatory syndrome, especially in patients with a low CD4 count on TB treatment. They can get a lot worse before they get better.

6. In patients with low CD4 counts, we give them sulphamethoxazole, trimethoprim.

Don’t give this with ARVs. Start ARVs for a week or two and then start Purbac.

Monitor renal function and when CD4s have picked up, drop Purbac.

7. When switching patients from one regimen to another, you need to know what you are doing. Make sure that the viral loads are undetectable. If the VLs are detectable, adherence is the most important thing. If you still can’t get the

VL down, you need to switch regimens.

8. Understand virological failure and do the right thing.

9. Keep in mind that lots of patients have hepatitis B. If you are taking patients off

TDF, do a Hep B surface antigen test. If patients are positive, we need to keep the TDF.

10. In terms of pregnancy, all women on

ARVs need to be virally undetectable.

For new patients who are HIV negative, we need to retest every three months, as 12% of women can seroconvert towards the end of pregnancy.