Tables and Figures

Table 1: Most frequent non-immune mediated adverse reactions reported to currently utilized antiretroviral drug

Drug

Gastrointestinal

Neurological

Renal (biochemical)

Renal (obstructive)

Metabolic

Musculoskeletal

Hepatic

Respiratory

Cutaneous (non-rash)

Nucleoside reverse transcriptase inhibitors (NRTI)

Abacavir

+

-

+

-

++^

-

-

-

-

Lamivudine

+

+ °

-

-

+^

-

+

-

-

Emtricitabine

++

-

-

-

+^

-

-

+ (cough)

+ (skin discolouration)

Tenofovir disoproxil fumurate (TDF)

+

+ °

*

-

+^

++‡

-

-

-

Tenofovir alafenamide fumurate (TAF)

+

+ °

-

-

+^

-

-

-

-

Non-nucleotide reverse transcriptase inhibitors (NNRTI)

Nevirapine

+

+

-

-

-

-

++

-

-

Efavirenz

-

+++

-

-

+ (lipids, lipodystrophy)

-

+

-

-

Etravirine

-

-

-

-

-

-

-

-

-

Rilpivirine

-

+

-

-

+/-

-

+/-

-

-

Protease inhibitor

Atazanavir

+

+

-

+/-

+ *‡

+†

++

-

-

Darunavir

++

+

-

-

+ (TG) *‡

+†

-

-

-

Integrase inhibitor

Raltegravir

+

+

-

-

-

+ (rhabdomyolysis)

-

-

-

Dolutegravir

+

+

-

-

-

-

-

-

-

Bictegravir

+

+

-

-

-

-

-

-

-

Eltegravir

+

+

-

-

-

-

-

-

-

Only drugs currently recommended by ASHM and initial and continuing regimens are included in the analysis – Tenofovir, emtricitabine, lamivudine, efavirenz, dolutegravir, bictegravir, elvitegravir, raltegravir, darunavir, atazanavir, rilpivirine.

Abbreviations – OP, osteoporosis; TG, hypertrigylceridemia

+ Mild or infrequent reports; ++ Moderate or not uncommon reports; +++ Severe or frequent

^ hyperlactatemia/lactic acidosis

† fat redistribution

‡ Increased risk of osteoporosis

*Diabetes/hyperglycemia

°Headache only

Table 2: Pharmacogenomic predictors of drug hypersensitivity reactions in people with HIV infection

Drug

Phenotype

HLA

Population

PPV

NNP

NNT

Nevirapine

SJS/TEN

HLA-C*04:01

? CYP2B6 983 T-C

African (Malawian)

Mozambique

ND

Rash

HLA-B*35:05

HLA-Cw4

Thai, African, Asian, European

White, Black, Asian Han, Chinese

16%

97%

ND

DRESS

HLA-B*14/Cw8

HLA-Cw*8 or

HLA -B*35

HLA -B*35:05

HLA -B*35:01

CYP2B6 516 G-T+C*04

CYP2B6 (rs2054675, rs3786547, rs3745274)

Italian

Japanese

Asian

Asian (Thai)

European/Australian

White, Black, Asian

White, Black, Asian

ND

Delayed rash (non-specific)

B*35:05; RS1576*G CCHR1 status (GWAS)

Thai

Hepatitis

HLA-DRB1*01:01 (CD% > 25) and DRB1*01:02

Australian, European, South African

18%

96%

Abacavir

Hypersensitivity syndrome

HLA-B*57:01

European, African

55%

100%

13

Dapsone

Rash, hepatitis

HLA-B*13:01

Chinese

7.8%

99.8%

84

Efavirenz

Delayed rash (non-specific)

DRB1*01

French

ND

Raltegravir

DRESS

HLA-B*53:01

African/Hispanic

ND

Sulfamethoxazole

SJS/TEN

HLA-B*38

European

ND

INR = international normalised ratio.

* Indications for assessment by a liver transplant centre include Child–Pugh score ≥ B7, MELD score ≥ 13 or one of the following clinical events: refractory ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, recurrent or chronic hepatic encephalopathy, small hepatocellular carcinoma or severe malnutrition.