HIV/AIDS

Antiretroviral therapy

Treatment or therapy is classified by the MOA of the drugs

Over 30 agents fall into these six classes.

Agents are usually used from 2 or 3 of these classes to ensure a powerful attack on HIV, thereby increasing efficacy of treatment and reducing the development of resistance.

• nucleoside reverse transcriptase inhibitors

• non-nucleoside reverse transcriptase inhibitors

• integrase inhibitors

• protease inhibitors

• entry inhibitors

• fusion inhibitors

Very important that HIV is detected as early as possible and treatment is started as early as possible to delay AIDS related infections, reduce morbidity and mortality, reduce onward transmission to the person’s partner.

START study demonstrated a 75 % risk reduction of AIDS and serious non AIDS related health outcomes amongst participants who began HRT when CD4 T Cell counts were greater than 500, compared with those who did not start or those whose CD4 count was too low, or developed AIDS

Some tests before starting treatment

Viral load and CD4 cell count

Baseline resistance testing - genotypic resistance testing of reverse transcriptase and protease enzymes in people who have not had ART before. Baseline integrase resistance is carried out is come instances e.g. if some mutations to the other drug classes are detected.

HIV Type 1 or Type 2 - drugs from NNRTI class are not effective against HIV 2, majority of infection is HIV1. For HIV2 regimens such as integrase inhibitor or protease inhibitor are recommended.

Hepatitis B co-infection/TB co-infection - if they have HEPB then the regimen must include 2 drugs which are effective against both infections. If they have TB then they will most likely be on rifampicin which is an enzyme inducer - has lots of interactions with HIV medications.

HLA-B *5701 typing - if they test positive for this then they will have hypersensitivity reaction to one of the drugs called abacavir so the drug needs to be avoided.

Renal and hepatic function - some drugs are toxic and require dosage adjustment.

Co-morbidities and CVS risk - some drugs have CV side effects so those options will need to be excluded.

Drug interactions

Monitoring during treatment - see if the viral load is reducing until it is undetectable, CD4 should gradually increase within normal levels of 500 to 1500 cells. If CD4 count is really low, prophylactic treatment would be offered to prevent other infections from occurring, e.g. cotrimoxazole to prevent pneumonia, until CD4 rises to above 200. If undetectable viral load then that means they can’t pass on the HIV to other individuals through sex.

However this is not a cure, the HIV is still present and missing doses will lead to viral load increasing again.

What to start with

BHIVA guidelines 2022

Adults, HIV1

Most people start HIV treatment on two drugs from the Nucleoside/nucleotide reverse transcriptase inhibitors (NRTI backbone)

Combined with either one integrase inhibitor or one non-nucleoside reverse transcriptase inhibitor or one protease inhibitor

Triple therapy'

Undetectable viral load.

Tenofovir is one of the most widely used medications for HIV and combination therapy. Two forms available which are both very effective.

Tenofovir DX is a salt while Tenofovir AF is alafenamide. Generally safe and well-tolerated, but may cause kidney problems and bone loss in some

both are pro-drugs. af is broken down inside the cells, is absorbed more quickly and produces higher levels of active drug which is tenofovir diphosphate in the cells - therefore it can be given in smaller doses, leading to lower drug levels in the blood and less exposure for the kidneys - less renal problems, and problems with bones

Response to treatment and treatment failure

Achieve viral suppression with undetectable viral load (<50 copies/ml)

Within 12 - 24 week of treatment (treatment naive)

Sustained improvement in CD4 cell response

Failure

• lack of adherence, drug resistance - something you have to take regularly for the rest of your life.

• Drug drug interactions, persistent side effects

• virological failure - VL not suppressed/rebound - resistant test and ART switch (1st time failures)

• Immunological failure - CD4 cells counts may not improve - difficult to treat, ART switch, disease progression.

Examples of special considerations

Pregnancy - toxicity/teratogenicity/treating mother/preventing transmission

Breast feeding - advice - give baby formula rather than milk, transmission through breast milk risk is low if HIV viral load is undetectable. Mother and child would be offered extra checks as well.

Hepatitis B co-infection, TB co-infection - HIV + HEPB patients should use combination antiretroviral therapy containing tenofovir plus wither lamivudine or emtricitabine - 2 drugs that are active against both these condition

Children - different natural progress, special treatment

Post exposure prophylaxis - combination of drugs that can stop the virus taking hold. Used if person is at risk of HIV transmission and must be taken within 72 hours and ideally should be taken within 24 hours post exposure

Pre - exposure prophylaxis - reduce chances of getting the virus, for example for someone whose partner is HIV positive. Its available as a tablet and needs to be taken before they have sex and are exposed to HIV

NRTI’s

• act on viral reverse transcriptase enzymes

• tenofovir

• emtricibitane

• abacavir

  • caution if HIV load>100000copies/ml

  • and if high risk CVD

  • Life threatening hypersensitivity reactions

  • increased risk if HLA-B *5701 allele present - pre treatment screening

  • lamivudine

  • other

  • life threatening lactic acidosis reported

  • use with caution in chronic hepatis B or C

  • greater risk of hepatic side effects

  • lipodystrophy syndrome

  • osteonecrosis

  • see BNF

Protease inhibitors

Bind to viral protease enzyme blocking cleavage of viral amino acids chain to constituent proteins

Ritonavir in low dose boosts activity (inhibits metabolism of other PI’s)

Metabolised by cytochrome p450

drug interactions

Lipodystrophy and metabolic effects

Osteonecrosis

Boosted protease inhibitors

Low dose ritonavir boosts the activity of other PI, giving higher levels and better potency and less likely for the devleopment of resistance.

• Atazanavir/ritonavir

• lopinavir/ritonavir

• darunavir/ritonavir

• fosemprevanir/ritonavir

Low dose ritonavir

• no intrinsic antiviral activity

• boosts activity of other PI

• Higher levels

• better potency

• more flexible dosing

• less likely to develop resistance.

Lipodystrophy syndrome

• Fat distribution to different parts of the body, and can get distressing side effects

• older drugs - less likely with newer medicines

• more likely to occur with combinations of drugs from NRTI’s and protease inhibitor classes

• metabolic affects - fat redistribution, insulin resistance, dyslipidaemia

• CVD risk factors before starting treatment

• lifestyle changes to reduce CVS risk

• monitor plasma lipids and blood glucose before and during therapy

• dyslipidaemia - esp. with pls

• Insulin resistance and hyperglycaemia - pls and some NRTI’s

Other problems with ART

Immune reconstitution inflammatory syndrome (IRIS)

• first few weeks/months

• immune system improves

• recovers too quickly - overworks

• Overwhelming inflammatory reaction

• against previously residual opportunistic organisms

• symptoms get much worse

• or may resolve on its own

Osteonecrosis

• advanced HIV

• long term therapy

Counselling

• people living with HIV are given the opportunity to contribute to decisions about their treatment

• provision of treatment - support resources

• adherence is crucial - tailor regime to suit daily lifestyle

• reducing transmission to partners, U = U

• Prevent development of viral resistance

• advice on side effects - short and long term

• drug interactions

• lifestyle/psychological counselling/stigma