Clinical chemistry laboratory analysis constitutes a key step in patient assessment for initiating and monitoring response to anti-retroviral treatment . The reliability and accuracy of clinical chemistry analytes, however, is confounded by complex interaction between injection drug use and anti-retroviral drugs. Therefore, this cross-sectional clinical laboratory study determined the clinical chemistry markers in HIV infected and uninfected injection heroin users from coastal Kenya.
Absolute albumin levels and albumin to total protein ratio reductions observed in the HIV-1 infected injection drug users are indications of derangements in protein metabolism. The decreases in the albumin levels can be attributed to low dietary intake of proteins that is linked to low synthesis of albumin , a feature of malnutrition that is frequently observed among injection drug users presenting with and without HIV infection . It is also possible that suppression of albumin results from inhibition of hepatic synthesis at abusive doses of heroin . In addition, opioid-induced hepatotoxicities and inflammatory-mediated hepatic damage cause reduced hepatic synthetic functions [15, 21]. Thus, findings presented here suggest that injection heroin use among HIV-infected individuals promote increased reductions in the albumin levels and marked alterations in the albumin to total protein ratio.
The inverse associations of HIV viral load and albumin to total protein and albumin to globulin indices in the anti-retroviral-naive injection heroin users signify disease progression but during treatment the albumin to globulin ratio is inverted indicating reductions in the viral loads and immune reconstitution. This premise is, in part, consistent with clinical studies in HIV infected patients commencing highly active anti-retroviral therapy showing that hypoalbuminaemia is associated with morbidity and mortality [22, 23]. Therefore, reduced albumin and low albumin to total protein ratio are important laboratory measures in injection heroin users that can be utilized as important surrogates for screening and for initiating and monitoring of anti-retroviral treatment in HIV infected injection heroin users.
In contrast to previous studies, a higher globulin level was found in the HIV infected injection heroin users naive for anti-retroviral treatment . This finding suggests that hyperglobulinaemia is an important laboratory marker of HIV infected patients injecting illicit drugs. Hyperglobulinaemia characterizes B cell dysfunction during primary HIV infections and persisting into chronic infections . The lower median albumin to globulin values in the presence of higher proportions of ratios ≤1.0, and the correlations of HIV viral loads with globulin in the anti-retroviral treatment-naive individuals, further corroborate increased derangements in B cell functions in both HIV infected and uninfected injection heroin users. The findings of the current study also parallel studies showing elevated globulin and the albumin to globulin ratio in Australian drug addicts . In addition, elevations in total IgM and IgG, specific anti-morphine IgM, and cross-reactive IgM auto-antibodies were recorded in HIV infected and uninfected opioid users [25–27]. Hence, it appears heroin-induced antibodies promote inflammation leading to liver damage in injection users. Elevated globulin with concomitant lower albumin to globulin ratio may thus be a useful biomarker for clinical laboratory assessment of HIV infected and uninfected injection heroin users.
Reduced absolute ALT levels found in the HIV sero-negative injection heroin users, indicate reduced hepatic functionality. However, the higher AST to ALT ratio and proportions of AST to ALT ratio ≥2.0 in the HIV sero-negative and infected injection heroin users naive or on anti-retroviral treatment, suggest synergistic heroin and anti-retroviral drug-induced hepatic inflammation. These results are similar to observations showing that the AST to ALT ratio is a better measure of liver enzyme activity . In addition, the results are, in part, supported by the elevated AST, AST to ALT ratios, and higher proportions of ALT observed in patients on anti-retroviral treatment [10–12]. Since a large number of the injection heroin users in the present study were concomitantly consuming alcohol and khat, it is possible that these non-injection substances synergistically promote the alterations in the ALT levels [10, 29]. Importantly, the inverse correlations of absolute ALT levels and the CD4+ T cell counts in the HIV sero-negative injection heroin users, suggests that the CD4+ T cell count can also be utilized as a surrogate marker of liver function in the management of HIV negative heroin users.
The greater magnitude APRI median values and proportions ≥0.5 in the HIV infected injection heroin users on anti-retroviral treatment, suggests, that APRI is a better screening indicator of heroin and anti-retroviral treatment in this population. This observation is, in part, parallel to the time-dependent increases and prognostic value of APRI among HIV and hepatitis C co-infected patients undergoing anti-retroviral treatment , and studies in injection drug users showing the utility of APRI in predicting hepatic fibrosis . It is, therefore, likely that increased hepatotoxicity in HIV patients on anti-retroviral treatment results from the synergistic effect of anti-retroviral drugs, heroin and poly-substance consumption. Hence, APRI and proportions of APRI ≥0.5 are important measures for evaluating the degree of hepatoxicity in HIV infected injection heroin users undergoing anti-retroviral treatment.
Elevations of the C-reactive protein in all the study groups of injection heroin users is similar to previous studies showing elevated C-reactive protein in Australian drug addicts , and higher C-reactive protein levels in buprenorphine injection users in Singapore . Higher levels and proportions of individuals of this acute phase protein in both HIV infected and uninfected injection heroin users in the present study are indicative of increased liver synthesis following consumption of the illicit drugs, infection and cytokine release . In addition, the increases indicate heightened liver damage through illicit drug- and anti-retroviral treatment-mediated necrosis, apoptosis, and immune mechanisms. Of significance are analyses showing positive correlations between the C-reactive protein levels and the CD4+ T cell count in injection heroin users on anti-retroviral treatment. This result may reflect development of immune reconstitution inflammatory syndrome (IRIS) in the injection heroin users on anti-retroviral treatment resulting from poor adherence and illicit drug use. Consistent with this hypothesis, previous studies illustrated a link between IRIS and low adherence to anti-retroviral therapy, alcohol use, and low suppression of viral load among South African adults initiating anti-retroviral therapy . Implications of this observation include utilization of the C-reactive protein in assessing immune reconstitution following initiation of anti-retroviral treatment in injection heroin users.
Our results clearly show high rates of poly-drug use among injection heroin users in Mombasa. It is highly likely that the complex interactions of opioids and/or active compounds in bhang (Δ9-tetrahydrocannabinol), cigarettes (nicotine), rohypnol (benzodiazepines), alcohol, khat (cathinone), and anti-retroviral drugs promote the occurrence of drug dependence and adverse events. With regards to clinical chemistry profiles, such complex interactions induce hepatic metabolic derangements leading to toxicity and altered profiles of clinical chemistry markers. Consistent with these propositions, previous studies among drug users showed that interactions between opioids and benzodiazepines or alcohol increase occurrence of adverse events, overdose and death , as nicotine increase rates of opioid consumption . In addition, drugs of abuse (alcohol, opioids, benzodiazepines, marijuana, and nicotine) reduce the efficacy of anti-retroviral drugs leading to toxicity, treatment failure and high viral loads . Taken together, poly-drug use appears to promote toxicity leading to altered clinical chemistry profiles in both HIV-1 infected and uninfected injection drug users.
While a prospective design would have been important in examining the utility of clinical chemistry markers, in response to drug rehabilitation and HIV treatment, this cross-sectional study provides the first baseline information for screening of injection drug users for initiating and monitoring anti-retroviral treatments in Kenya. Although recruitment into this study was based on self-reported injection heroin use, it is possible that the study participants were also using other opioids, hence the need to carry out toxicological analyses to provide additional insights into the complex interactions between injection drugs and anti-retroviral treatment. These collectively can be linked to clinical laboratory markers and patient prognosis in a prospective approach.