KDR polymorphism (1192G/A, 1719A/T) and modulation of ARV drug-induced hepatotoxicity.

Kinase insert Domain containing Receptor (KDR)/Vascular Endothelial Growth Factor Receptor (VEGFR-2) participate in endothelial dysfunction, which can lead to chronic liver disease. KDR reflects naturally against the toxicants from the damaged liver cells. Association of KDR polymorphism has been reported with many diseases including liver disease, but its role has not been described in ARV induced hepatotoxicity. Hence, we examined the exonic regions KDR (1192G/A, 1719A/T) polymorphism from 165 HIV-infected individuals (34/165 had ARV induced hepatotoxicity, 131/165 were with no hepatotoxicity) and 160 normal uninfected individuals by PCR-RFLP. In univariate analysis, KDR 1719 TT genotype presented at greater frequency from all HIV positive individuals in contrast with normal uninfected individuals (7.87% vs. 4.4%, OR = 1.72, P = 0.38). Individuals with KDR 1719 TT genotype had a risk for increasing hepatotoxicity and its severity (OR = 1.91, P = 0.38). Individuals with haplotype AT had risk for increasing hepatotoxicity and its severity (OR = 1.60, P = 0.50; OR = 2.35, P = 0.27). Whereas haplotype AA was associated with reduced risk of developing hepatotoxicity (OR = 0.40, P = 0.04). Individuals with KDR 1719 TT genotype were at greater risk of advancement of HIV disease (OR = 2.31, P = 0.23). Individuals with KDR 1719 TT genotype had more vulnerability for developing hepatotoxicity among alcohol users (OR = 2.57, P = 0.23). Individuals with KDR 1719 TT genotype were at higher risk of developing hepatotoxicity and its severity among nevirapine and alcohol consumers (OR = 2.47, P = 0.24; OR = 5.42, P = 0.42). In multivariate analysis, hepatotoxicity patients taking ART inclusive of nevirapine was associated with the severity of hepatotoxicity (OR = 4.82, P = 0.002). In conclusion, KDR 1719 TT genotype and haplotype AT may have a risk for development of hepatotoxicity and its severity. Haplotype AA may have influence to reduce the risk of developing hepatotoxicity.

TLR7 Polymorphism (rs179008 and rs179009) in HIV-Infected Individual Naïve to ART.

Toll-like receptors (TLRs) play an important role in the innate immune response to HIV infection. Single nucleotide polymorphism (SNP) in TLR7 (Gln11Leu) gene has been associated with a rapid decline of CD4T cell count. Hence, we assessed the TLR7 (rs179008, Gln11Leu (A/T) and rs179009, IVS2-151 (A/G)) polymorphism in 150 HIV-infected individuals naïve to ART and 158 healthy controls. The genotyping of TLR7 Gln11Leu (A/T) and IVS2-151 (A/G) polymorphisms was done using the PCR-RFLP method. In univariate analysis, none of the genotype and haplotype of TLR7 Gln11Leu (A/T) and IVS2-151 (A/G) polymorphism differed significantly between HIV-infected individuals and healthy controls. The occurrence of TLR7 rs179009AG genotype in the codominant model and rs179009 AG-GG genotype in the dominant model was significantly reduced in HIV-infected individuals as compared to healthy controls (18.0% vs. 29.1%, OR = 0.42, P = 0.016; 26.7% vs. 36.7%, OR = 0.52, P = 0.016). TLR7 rs179009AG genotype was significantly underrepresented in the intermediate HIV disease stage compared with healthy controls (OR = 0.03, P = 0.04). TLR7 rs179009AG genotype expressed higher in tobacco-consuming HIV-infected individuals compared with nonusers (OR = 1.71, P = 0.47). In conclusion, rs179009 AG-GG and AG genotypes were found reduced in HIV-infected individuals as compared to healthy controls; their higher prevalence in health individuals clearly support that they are associated with reduced risk of acquisition of HIV-1 infection.

Interleukin-10 polymorphisms and susceptibility to ARV associated hepatotoxicity.

Interleukin-10 (IL-10) is an anti-inflammatory cytokine associated with the inhibition of HIV replication. IL-10 polymorphisms were found to be linked to drug-induced hepatotoxicity. Hence we examined the prevalence of IL-10 (-819C/T,-1082A/G) polymorphisms in a total of 165 HIV patients which included 34 patients with hepatotoxicity, 131 without hepatotoxicity and 155 healthy controls by the PCR-RFLP method. In HIV patients with hepatotoxicity, the IL-10-819TT genotype increased the risk of ARV associated hepatotoxicity severity (OR = 1.61, P = 0.35). IL-10-819TT genotype was overrepresented in patients with hepatotoxicity as compared to healthy controls (26.5% vs. 13.5%, OR = 1.61, P = 0.46). IL-10 -819CT genotype was associated with advance HIV disease stage (OR = 0.49, P = 0.045). In HIV patients without hepatotoxicity, the IL-10-819TT genotype was more prevalent in patients consuming tobacco as compared to non-users (OR = 1.60, P = 0.41). In HIV patients without hepatotoxicity using both alcohol + efavirenz along with IL-10 -819CT genotype resulted in increased risk for the acquisition of ARV associated hepatotoxicity (OR = 4.00, P = 0.36). In multivariate logistic regression, taking nevirapine was associated with the risk hepatotoxicity severity (OR = 0.23, P = 0.005). In conclusion, an insignificant association between IL-10 polymorphisms and susceptibility to ARV associated hepatotoxicity.

Polymorphisms in miRNAs Gene (146a, 149, 196a) and Susceptibility to ARV-associated Hepatotoxicity.

BACKGROUND: Micro RNAs act as a regulatory layer for pharmacogenomics-related gene ex-pression. It could play a role in the efficacy and toxicity of the drug. The SNPs in miRNA genes are linked with different functional consequences. METHODS: Hence, we examined the miR (146a G/C, 149C/T, and 196aC/T) polymorphisms in 34 pa-tients with hepatotoxicity, 123 patients without hepatotoxicity, and 155 healthy controls using a PCR-RFLP method. RESULTS: In patients with hepatotoxicity, miR196aCT genotype and combined genotype GCT showed a risk for hepatotoxicity severity with borderline significance (OR=2.08, P=0.07; OR=2.88, P=0.06). While comparing between patients with hepatotoxicity and healthy controls, the combined genotypes CCC and GCT have shown a susceptibility to hepatotoxicity severity (OR=2.89, P=0.05; OR=2.60, P=0.09). The miR196TT genotype was associated with the individuals of advanced HIV disease stage (OR=3.68, P=0.04). In HIV patients who consumed alcohol and did not have hepatotoxicity, the miR 196aCT genotype showed susceptibility to acquisition of hepatotoxicity with borderline significance (OR=2.36, P=0.06). DISCUSSION: The miR149TT and 196aTT genotypes showed a risk of acquisition of hepatotoxicity to nevirapine usage among HIV patients without hepatotoxicity (OR=4.19, P=0.07; OR=1.97, P=0.84). In HIV patients with and without hepatotoxicity, the miR 196aCT genotype showed a risk of acquisition of hepatotoxicity and its severity to the combined use of alcohol and nevirapine, respectively (OR=14.18, P=0.08; OR=2.29, P=0.08). In multivariate logistic regression, taking nevirapine, 196aCT genotype had an independent risk factor for hepatotoxicity severity (OR=5.98, P=0.005; OR=2.38, P=0.05).Conclusion: In conclusion, miR196aC/T polymorphism and combined genotypes GCT and CCC may facilitate the risk for acquisition of hepatotoxicity and its severity.

Tissue Inhibitor of Metalloproteinase-2 Polymorphisms and Risk for HIV-Associated Neurocognitive Disorder.

The imbalance between MMPs and TIMPs is associated with the HIV dissemination tissue damage pathology neurodegenerative disorders, including HAND. Genetic variations in the TIMP gene may modulate the neurocognitive disorder in HIV patients. Hence, we evaluated the genetic variants of TIMP-2 (-418G/C, 303G/A) gene with the risk of HAND. Genotyping of TIMP-2 polymorphism was performed in 50 patients with HAND, 100 no HAND, and 154 healthy controls by PCR-RFLP. TIMP-2 -418GC and 303AA genotypes represented a predominant risk for HAND severity (OR = 1.55, P = 0.30; OR = 4.58, P = 0.24). The variant -418CC genotype, -418A allele, had exhibited a significant risk for the acquisition of HAND (OR = 12.55, P = 0.026; OR = 2.66, P = 0.004). TIMP-2 303GA, 303AA genotype, and 303A allele evinced a higher risk for HAND severity (OR = 1.82, P = 0.14; OR = 1.70, P = 0.63; and OR = 1.68, P = 0.12). In HIV patients, TIMP-2 -418CC genotype and -418C allele significantly occurred in comparison to healthy controls (OR = 10.10, P = 0.006; OR = 2.02, P = 0.009). In the intermediate and early HIV disease stage, TIMP-2 -418CC genotype was significantly increased compared with healthy controls (11.1% vs. 1.3%, OR = 14.63, P = 0.01; 16.9% vs. 1.3%, OR = 14.51, P = 0.002). In patients with HAND among tobacco and alcohol users, TIMP-2 -418CC genotype displayed a risk for HAND severity (OR = 3.96, P = 0.26; OR = 4.83, P = 0.19). On multivariate logistic regression, TIMP-2 303AA genotype, advanced stage, and gender had a risk for HAND severity (OR = 28.98, P = 0.02; OR = 2.35, P = 0.070; and OR = 2.36, P = 0.04). In conclusion, TIMP-2 -418G/C polymorphism independently, along with alcohol and tobacco, may have an impact on the acquisition of HAND and its severity. TIMP-2 303G/A polymorphism bare a risk for HAND severity.

Impact of cellular restriction gene (TRIM5α, BST-2) polymorphisms on the acquisition of HIV-1 and disease progression.

BACKGROUND: TRIM5α and BST-2 are cellular restriction factors affecting the HIV-1 infection and its progression. Genetic variability in these genes alters the expression pattern. Hence, we aimed to examine the impact of the TRIM5α (rs10838525, rs7127617 and rs904375) and BST2 (rs3217318 and rs71694748) polymorphisms on the acquisition of HIV-1 and its progression. METHODS: Genotyping of TRIM5α and BST-2 polymorphisms was performed in a total of 153 HIV-infected patients and 158 unrelated healthy individuals using a polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: No significant differences were found in the genotype frequencies of TRIM5α polymorphisms between HIV patients and healthy controls. BST-2 Δ19/i19 and i19/i19+ Δ19/i19 genotypes appeared more frequently in HIV patients compared to healthy controls (10.4% versus 7.0%, p = 0.20; 11.10% versus 7.6%, p = 0.16). The BST-2 i19 allele was associated with the acquisition of HIV-1 [odds ratio (OR) = 2.76, p = 0.030)]. TRIM5α haplotypes ATG and ACA elevated the risk, whereas haplotype ATA reduced the risk for the acquisition of HIV-1 (OR = 1.92, p = 0.026; OR = 4.88, p = 0.016; OR = 0.31, p = 0.014). BST-2 Δ19/i19 and i19/i19+ Δ19/i19 genotypes were more prevalent in patients with early HIV disease stage compared to healthy controls (15.9% versus 7.0%, p = 0.096; 15.9% versus 7.6%, p = 0.12). The prevalence of TRIM5α rs7127617 CC and BST-2 Δ19/i19 genotypes was observed to be higher in alcohol-using HIV patients compared to non-users (27.8% versus 20.0%, p = 0.35, 22.2% versus 10.0%, p = 0.24). CONCLUSIONS: TRIM5α haplotypes and the BST-2 i19 allele may significantly affect the modulation of HIV-1 acquisition and its progression. TRIM5α rs7127617 CC and BST-2 Δ19/i19 genotypes in alcohol-using HIV patients elevated the risk of HIV disease progression.

IL-1RN and IL-1ß Polymorphism and ARV-Associated Hepatotoxicity.

The severity of hepatic injury depends upon cytokines. Previous studies associated IL-1RN allele 2 with IL-1ß production. Hence, we examined the association of IL-1 RN and IL-1ß polymorphisms with ARV-associated hepatotoxicity. Genotyping of IL-1RN (VNTR), IL-1ß (-511C/T) polymorphisms was done in 162 HIV-infected patients, 34 with ARV hepatotoxicity, 128 without hepatotoxicity, and 152 healthy controls using PCR and PCR-RFLP method. The haplotypes 1T and 2C enhanced the risk for severe hepatotoxicity (OR = 1.41, P = 0.25; OR = 1.67, P = 0.31). IL-1ß-511TT genotype significantly represented among tobacco using HIV-infected individuals compared to nonusers (OR = 3.74, P = 0.05). IL-1ß-511TT genotype among alcohol users increased the risk for hepatotoxicity (OR = 1.80, P = 0.90). IL-1ß-511CT and -511TT genotypes overrepresented in alcohol using HIV-infected individuals (OR = 2.29, P = 0.27; OR = 2.64, P = 0.19). IL-RN 2/2 and 1/3 genotypes represented higher in nevirapine using hepatotoxicity patients (OR = 1.42, P = 0.64, OR = 8.79, P = 0.09). IL-1ß-511CT and -511 TT genotypes among nevirapine users enhanced the risk for severe hepatotoxicity (OR = 4.29, P = 0.20; OR = 1.95, P = 0.56). IL-1ß-511CT and -511TT genotypes were overrepresented in combined nevirapine and alcohol using HIV-infected individuals as compared to nevirapine users and alcohol nonusers (OR = 2.56, P = 0.26; OR = 2.84, P = 0.24). IL-1ß-511TT genotype with tobacco, alcohol, and nevirapine usage revealed a trend of risk for the development of ARV-associated hepatotoxicity and its severity.

TLR3 polymorphisms in HIV infected individuals naïve to ART.

BACKGROUND: TLR3 polymorphisms affect the risk of HIV infection and modify the disease course. Consequently, we analyzed the association of TLR3 polymorphism (rs5743312, rs3775296, and rs3775291) with susceptilbity to HIV-1 acquisition and disease progression. METHOD: This is a cross-sectional study. Genotyping of TLR3 polymorphisms were completed by the utilization of the PCR-RFLP technique in 153 HIV naive subjects and 158 healthy controls. RESULT: A haplotype is a physical grouping of genomic variants that tend to be inherited together. The TCC haplotype was increased in HIV infected individuals compared with healthy controls (0.05% versus 0.03%). TLR3 rs3775291CT genotype was associated to the early stage of HIV infection (OR=2.19, P=0.04), with a higher occurrence in advance stage of HIV infection when contrasted with healthy controls (41.2% versus 32.3%). TLR3 rs3775296 CA genotype was likely to be associated with intermediate stage of HIV infection (19.5% versus 31.6%, OR=0.42, P=0.06). TLR3 rs5743312TT genotype was used to be greater prevalence in advanced stage of HIV infection compared with healthy controls (2.9% versus 1.9%). TLR3 rs3775296CA genotype was less prevalent in HIV subjects devouring tobacco when contrasted with non-users (9.1% versus 34.9%, OR=0.25, P=0.09). TLR3 rs3775296AA and rs3775291CT and TT genotypes have been overrepresented in HIV subjects using alcohol when contrasted with non-users (5.6% versus 1.1%, OR=1.83, P=0.67; 50.0% versus 42.2%, OR=1.84, P=0.31; 5.6% versus 3.3%, OR=2.70, P=0.50). In multivariate examination, rs5743312TT genotype showed a greater risk for HIV infection (OR=1.86, P=0.50). CONCLUSION: TLR3 rs3775291 C/T polymorphism may assist the risk of disease progression in alcohol consumers. TLR3 rs3775291 CT genotype may enhance the disease progression whereas the TLR3 rs3775296 CA genotype may protect for disease progression.

Occurrence of Interleukin-2 (330 G/T) Promoter Polymorphism in ARV associated hepatotoxicity.

BACKGROUND: IL-2 cytokine is involved in HIV replication and is also known to cause hepatic injury. Polymorphisms in the IL-2 gene are associated with altered interleukin-2 production. METHODS: Hence, we assessed the prevalence of IL-2-303G/T polymorphism in 165 HIV patients (34 with and 131without hepatotoxicity) and 155 healthy controls using the PCR-RFLP method. RESULTS: In patients with hepatotoxicity, IL-2-303GT, -303GT+TT genotypes were less prevalent as compared to without hepatotoxicity and healthy controls (29.4% vs. 42.7%, 58.8% vs. 69.5%; 29.4% vs. 40.6%, 58.8% vs. 66.5%, respectively). In patients with hepatotoxicity using tobacco and alcohol, IL-2-303GT,-303TT genotypes were distributed higher as compared to non-users (42.9% vs. 25.9%, OR=8.52, 42.9% vs. 25.9%, OR=9.09, and 28.6% vs. 29.6%, OR=1.63, 42.9% vs. 25.9%, OR=2.93), while IL-2-303TT genotype occurred more often in HIV patients consuming alcohol (34.1% vs. 23.0%). Nevirapine users with hepatotoxicity overrepresented the IL-2-303GT,-303TT genotypes as compared to efavirenz (34.8% vs. 18.2%, OR=4.64, 34.8% vs. 18.2%, OR=3.88). Among nevirapine users, IL-2-303GT genotype was associated with susceptibility to the acquisition of hepatotoxicity with borderline significance (OR=4.24, P=0.06). HIV patients using nevirapine majorly represented the IL-2-303TT genotype (26.9% vs. 25.0%, OR=2.35) while HIV patients with nevirapine + alcohol usage presented the IL-2 -330TT genotype at a higher frequency (34.2%% vs. 23.5%, OR=1.51). In patients with hepatotoxicity using nevirapine + alcohol, the genotype IL-2 - 330TT was predominant (60.0% vs. 27.8%, OR=3.16). CONCLUSION: Thus, IL-2-303G/T polymorphism did not confer the susceptibility to ARV associated hepatotoxicity. However, IL-2-303G/T polymorphism with nevirapine usage may facilitate the risk for acquisition of ARV associated hepatotoxicity.

Effect of matrix metalloproteinase-21 (572C/T) polymorphism on HIV-associated neurocognitive disorder.

Remodeling of extracellular matrix (ECM) by matrix metalloproteinases (MMPs) is a presumed reason for the development of HIV-associated neurocognitive disorders (HAND). The coding region polymorphism in MMP-21 572C/T gene may have a potential functional effect on ECM remodeling. Hence, we aimed to examine the association of MMP-21 polymorphism with the modulation of HAND severity and its prevalence in HIV-infected and healthy individuals. Genotyping of MMP-21 572C/T polymorphism was performed by PCR-RFLP in total 150 HIV-infected individuals, 50 with HAND, 100 without HAND and 150 healthy controls. MMP-21 572TT genotype was predominantly higher in HAND patients compared with no HAND (OR = 1.63, p = 0.57). MMP-21 572T allele was associated with reduce risk for HAND severity (OR = 0.50, p = 0.04). Similarly, MMP-21 572TT genotype underrepresented in HIV-infected individuals compared to healthy controls (3.0% vs 6.7%, OR = 0.27, p = 0.08). MMP-21 572CT genotype and early HIV disease stage showed a higher risk for the advancement of HIV disease with marginal significance (OR = 1.89, p = 0.07). MMP-21 572CT genotype increased the risk for the modulation of HAND severity in tobacco users (OR = 1.98, p = 0.43). MMP-21 572CT genotype among tobacco and alcohol users showed elevated risk for the development of HAND in HIV-infected individuals (OR = 2.30, p = 0.15; OR = 1.86, p = 0.23). Similarly, MMP-21 572TT genotype enhanced the risk for the development of HAND in tobacco users (OR = 3.48, p = 0.40). In conclusion, the presence of coding region 572T allele may have protection for HAND severity. MMP-21 572C/T polymorphism and tobacco and alcohol usage may facilitate the development of HAND.

Prevalence of MMP-8 gene polymorphisms in HIV-infected individuals and its association with HIV-associated neurocognitive disorder.

Matrix metalloproteinases (MMPs) are well-known as mediators of neuroinflammation in HIV-associated neurocognitive disorder (HAND). Increased levels of MMP-8 have been observed in the HIV-infected patients. Thus, the aim of this study was to evaluate the association of MMP-8 gene polymorphisms with modulation of HAND severity and its prevalence in HIV-infected and healthy individuals. We enrolled a total of 150 HIV-infected individuals, 50 HAND patients, 100 HIV-infected and 150 healthy individuals. MMP-8 (-799C/T, +17C/G) polymorphisms were genotyped by PCR-RFLP. MMP-8 -799TT genotype and +17G allele showed the higher risk for modulation of HAND severity (OR=2.20, P=0.19; OR=1.97, P=0.23). MMP-8 -799TT genotype differed significantly in HIV-infected individuals compared to healthy controls (20.0% vs. 11.3%, OR=2.36, P=0.048). Haplotype TG increased the risk for modulation of HAND severity (OR=2.29, P=0.29). MMP-8 -799TT and +17CG genotypes were overrepresented in the intermediate HIV disease stage compared with healthy controls (25.9% vs. 11.3%, OR=4.34, P=0.021, 14.8% vs. 9.3%, OR=2.88, P=0.11). MMP-8 +17CG genotype enhanced the risk for modulation of HAND severity in tobacco using HAND patients (OR=5.01, P=0.17). MMP-8 -799TT genotype was more frequent in tobacco using HIV-infected individuals compared with nonusers (26.3% vs. 16.7%, OR=2.08, P=0.32). MMP-8 +17CG genotype increased the risk for modulation of HAND severity in alcohol using HAND patients (OR=4.99, P=0.18). In conclusion, MMP-8 polymorphisms independently and with alcohol and tobacco usage revealed a trend of higher risk for the modulation of HAND severity. MMP-8 -799TT genotype was associated with the advancement of HIV disease.

Promoter polymorphism MMP-1 (-1607 2G/1G) and MMP-3 (-1612 5A/6A) in development of HAND and modulation of pathogenesis of HAND.

The pathogenesis of HIV-associated neurocognitive disorder (HAND) is modulated by host genetic susceptibility factors such as Matrix metalloproteinases (MMPs). Promoter polymorphism of MMP-1 and MMP-3 may modify the expression of the gene. Hence, we evaluated the association of MMP-1-16072G/1G and MMP-3-1612 5A/6A polymorphisms with development of HAND and the modulation of pathogenesis of HAND. We enrolled a total of 180 individuals, 50 HIVinfected individuals with HAND, 130 without HAND, and 150 healthy controls. Polymorphism of MMP-1 and MMP-3 were genotyped by PCR-RFLP. MMP-1-1607 2G1G, -16071G/2G-1G/1G genotypes and -1607 1G allele were associated with the development of HAND (OR = 1.64, P = 0.05; OR = 1.45, P = 0.04; OR = 1.69, P = 0.05). MMP-1- 16071G1G, MMP-3-16125A5A genotypes increased the risk for the development of HAND (OR = 1.78, P = 0.25; OR = 2.39, P = 0.13). MMP-3-1612 5A5A, -1612 6A/5A-5A/5A genotypes and -1612 5A allele were associated with the reduced risk of HAND (OR = 0.40, P = 0.05; OR = 0.53, P = 0.04; OR = 0.40, P = 0.01). Haplotype 5A1G increased the risk of development of HAND (OR = 1.93, P = 0.05). As observed in advanced HIV disease stage, MMP-1-1607 1G1G genotype enhance the risk for advancement of HIV disease (OR = 1.69, P = 0.89). MMP-3-1612 6A5A genotype showed higher risk for development of HAND in alcohol users (0R = 1.65, P = 0.44). MMP-1 genotype may have an influence on development of HAND whereas MMP3-1612 5A5A genotype may reduce risk for pathogenesis of HAND.

CYP1A1m1 and CYP2C9*2 and *3 polymorphism and risk to develop ARV-associated hepatotoxicity and its severity.

Non-nucleoside reverse transcriptase inhibitors are metabolized in the liver by cytochrome P450 (CYP) isoenzymes. Variations in the genes encoding these enzymes may influence the activity of corresponding metabolizing enzymes. This study aimed at assessing association of CYP2C9*2 430C/T, CYP2C9*31075A/C, and CYP1A1m1 3801T/C polymorphism with risk to develop ARV Antiretroviral-associated hepatotoxicity and its severity. In this case-control study, genotyping of CYP2C9*2, CYP2C9*3, and CYP1A1m1 genes was done in 34 HIV-infected individuals with hepatotoxicity and 131 without hepatotoxicity, and 153 unrelated healthy individuals using PCR-RFLP. CYP1A1m13801CC genotype was likely to be associated with severe ARV-associated hepatotoxicity (OR = 1.78, p = 0.70). CYP1A1m13801CC genotype and combined genotype TC + CC were likely to be associated with development of ARV-associated hepatotoxicity (OR = 2.57, p = 0.08; OR = 1.42, p = 0.17). CYP1A1m1 3801CC genotype among advanced and intermediate HIV disease stage was likely to be associated with advancement of disease (OR = 2.56, p = 0.77; OR = 2.37, p = 0.45). CYP2C9*31075AC genotype among alcohol users was likely to be associated with development of ARV-associated hepatotoxicity (OR = 1.67, p = 0.38). CYP1A1m1 3801TC genotype and combined genotype TC + CC among nevirapine users were likely to be associated with severe ARV-associated hepatotoxicity (OR = 3.68, p = 0.27; OR = 4.91, p = 0.13). Among those who received nevirapine, presence of CYP1A1m1 3801TC genotype was likely to be associated with increased risk of development of ARV-associated hepatotoxicity (OR = 1.50, p = 0.78). CYP1A1m1 3801TC, 3801CC, and CYP2C9*3 1075AC genotypes among combined alcohol + nevirapine users increased the risk of development of ARV-associated hepatotoxicity (OR = 1.41, p = 0.53; OR = 1.49, p = 0.83; OR = 1.78, p = 0.35). In conclusion, individuals with CYP1A1m13801CC and 3801TC genotypes independently and in the presence of alcohol and nevirapine usage is likely to be associated with increased risk of development of ARV-associated hepatotoxicity, its severity, and advancement of disease. CYP2C9*31075AC genotype with combined alcohol and nevirapine usage indicated a risk for development of ARV-associated hepatotoxicity.