Antiretroviral Therapy and Alcohol Interactions: X-raying Testicular and Seminal Parameters Under the HAART Era

  • Oluwatosin O. Ogedengbe
  • Edwin C. S. Naidu
  • Onyemaechi O. Azu
Review Article


The prevalence of alcohol use among HIV-infected patients undergoing antiretroviral (ARV) treatments has raised several concerns related to key therapeutic indices. These include drug interactions, compliance, efficacy and toxicity with the possibility of accelerated disease progression. Interaction of ARVs with alcohol can result in therapeutic failures or place patients at significant risk for toxicities. Research findings in this particular area are, however, limited and sometimes conflicting. This review focuses on alcohol and ARV interactions affecting testicular and spermatogenic indices. Antiretroviral drugs are known to negatively impact testicular functions via altered mitochondrial DNA and oxidative stress mechanisms. Interaction with alcohol can significantly affect seminal fluid concentration of ARVs. Habitual consumption of alcohol causes testicular hypofunction with potential for lowered fertility. Concomitant use of ARVs appears to act synergistically to exacerbate this toxicity. Alcohol also induces cytochrome P450 (CYPs) microsomal enzymes, which in turn affect ARVs metabolized by these enzymes. In the presence of ARVs with strong inhibitory activity, increased bioavailability with toxicities predominates. In addition, alcohol and ARVs have pronounced effects on membrane-associated drug transporters. Alcohol alters the properties of the lipid bilayer by changing membrane permeability and protein distribution. Since drug transporters critical to pharmacokinetics are integral membrane proteins, alcohol tends to diminish the activity of both the efflux and influx transporters. While excessive alcohol precipitates accelerated hypogonadism, future research needs to be directed to quantifying these effects of alcohol and ARVs in human testicular tissue.



The College of Health Sciences, University of KwaZulu-Natal, is acknowledged for postgraduate support to the first author. This work is supported in part by the National Research Foundation of South Africa to the senior author (Unique Grant no. 94018). Our special thanks are due to Mr. Adeniji Femi Emmanuel for his generous assistance and support.

Compliance with Ethical Standards

Conflict of interest

None declared by all the authors.


No sources of funding were used to prepare this review.


  1. 1.
    UN Joint Programme on HIV/AIDS (UNAIDS), UNAIDS DATA-2017. Accessed 7 Sept 2017.
  2. 2.
    Williams BG, Gouws E, Somse P, Mmelesi M, Lwamba C, Chikoko T, et al. Epidemiological trends for HIV in southern Africa: implications for reaching the elimination targets. Curr HIV/AIDS Rep. 2015;12(2):196–206.PubMedCrossRefGoogle Scholar
  3. 3.
    Shisana O, Rehle T, Simbayi L, Zuma K, Jooste S, Zungu N, et al. South African national HIV prevalence, incidence and behaviour survey. 2012. Accessed 7 Sept 2017.  
  4. 4.
    Okoror TA, BeLue R, Zungu N, Adam AM, Airhihenbuwa CO. HIV positive women’s perceptions of stigma in health care settings in Western Cape, South Africa. Health Care Women Int. 2014;35(1):27–49.PubMedCrossRefGoogle Scholar
  5. 5.
    Eaton JW, Bacaër N, Bershteyn A, Cambiano V, Cori A, Dorrington RE, et al. Assessment of epidemic projections using recent HIV survey data in South Africa: a validation analysis of ten mathematical models of HIV epidemiology in the antiretroviral therapy era. Lancet Glob Health. 2015;3(10):e598–608.PubMedCrossRefGoogle Scholar
  6. 6.
    Pitpitan EV, Kalichman SC, Eaton LA, Sikkema KJ, Watt MH, Skinner D, et al. Men’s behavior predicts women’s risks for HIV/AIDS: multilevel analysis of alcohol-serving venues in South Africa. Prev Sci. 2016;17(4):472–82. doi: 10.1007/s11121-015-0629-9.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Probst C, Simbayi LC, Parry CD, Shuper PA, Rehm J. Alcohol use, socioeconomic status and risk of HIV infections. AIDS Behav. 2017;21(7):1926–37.PubMedCrossRefGoogle Scholar
  8. 8.
    Velloza J, Watt MH, Abler L, Skinner D, Kalichman SC, Dennis AC, et al. HIV-risk behaviors and social support among men and women attending alcohol-serving venues in South Africa: implications for HIV prevention. AIDS Behav. 2017;1–11.doi: 10.1007/s10461-017-1853-z.
  9. 9.
    Arenas-Pinto A, Milinkovic A, Peppa D, McKendry A, Maini M, Gilson R. Systemic inflammation and residual viraemia in HIV-positive adults on protease inhibitor monotherapy: a cross-sectional study. BMC Infect Dis. 2015;15(1):138.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Tabe FN, Yanou NN, Kamdje AHN, Ntso A-SA. Oxidative role of HIV/AIDS: antiretroviral drugs and medicinal plants with anti-HIV activity. JDMP. 2015;1(5):68–75.CrossRefGoogle Scholar
  11. 11.
    Nagiah S, Phulukdaree A, Chuturgoon A. Mitochondrial and oxidative stress response in HepG2 cells following acute and chronic exposure to antiretroviral drugs. J Cell Biochem. 2015;116(9):1939–46.Google Scholar
  12. 12.
    Onyebueke G, Fe O. Depression and suicide risk among HIV positive individuals attending an outpatient HIV/AIDS clinic of a Nigerian Tertiary Health Institution. J Psychiatry. 2015;18:182. doi: 10.4172/Psychiatry.1000182.
  13. 13.
    Palfai T, Cheng D, Coleman S, Bridden C, Krupitsky E, Samet J. The influence of depressive symptoms on alcohol use among HIV-infected Russian drinkers. Drug Alcohol Depend. 2014;134:85–91.PubMedCrossRefGoogle Scholar
  14. 14.
    Stewart SH, Zeitlin SB. Anxiety sensitivity and alcohol use motives. J Anxiety Disord. 1995;9(3):229–40.CrossRefGoogle Scholar
  15. 15.
    Crocq M-A. Alcohol, nicotine, caffeine, and mental disorders. Dialogues Clin Neurosci. 2003;5(2):175.PubMedPubMedCentralGoogle Scholar
  16. 16.
    WHO. World health statistics 2016 data visualizations dashboard: harmful use of alcohol. 2016. Accessed 07 Dec 2016.
  17. 17.
    Organization WH. Global Status Report on Alcohol and Health 2011. Geneva: World Health Organization; 2011 (Country Profiles: South Africa).Google Scholar
  18. 18.
    Peltzer K, Ramlagan S. Alcohol use trends in South Africa. J Soc Sci. 2009;18(1):1–12.Google Scholar
  19. 19.
    Ramsoomar L, Morojele NK. Trends in alcohol prevalence, age of initiation and association with alcohol-related harm among South African youth: implications for policy. SAMJ S Afr Med J. 2012;102(7):609–12.PubMedCrossRefGoogle Scholar
  20. 20.
    Bello B, Moultrie H, Somji A, Chersich MF, Watts C, Delany-Moretlwe S. Alcohol use and sexual risk behaviour among men and women in inner-city Johannesburg, South Africa. BMC Public Health. 2017;17(3):65.PubMedCentralGoogle Scholar
  21. 21.
    Garcia LP, Freitas LRS. Heavy drinking in Brazil: results from the 2013 National Health Survey. Epidemiologia e Serviços de Saúde. 2015;24(2):227–37.CrossRefGoogle Scholar
  22. 22.
    Organization WH, Unit WHOMoSA. Global status report on alcohol and health, 2014. Geneva: World Health Organization; 2014.Google Scholar
  23. 23.
    Jackson KM. Heavy episodic drinking: determining the predictive utility of five or more drinks. Psychol Addict Behav. 2008;22(1):68.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Schneider M, Chersich M, Temmerman M, Degomme O, Parry CD. The impact of alcohol on HIV prevention and treatment for South Africans in primary healthcare. Curationis. 2014;37(1):01–8.CrossRefGoogle Scholar
  25. 25.
    Evidence WHOMH, Team R. Alcohol use and sexual risk behaviour: a cross-cultural study in eight countries. Geneva: World Health Organization; 2005.Google Scholar
  26. 26.
    Young SV, Wood E, Dong H, Kerr T, Hayashi K. Daily alcohol use as an independent risk factor for HIV seroconversion among people who inject drugs. Addiction. 2016;111(8):1360–5.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Bassols AMS, Boni RD, Pechansky F. Alcohol, drugs, and risky sexual behavior are related to HIV infection in female adolescents. Revista Brasileira de Psiquiatria. 2010;32(4):361–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Simbayi L, Kalichman S, Jooste S, Cain D, Kaufman M. Alcohol use and sexual risks for HIV/AIDS in sub-Saharan Africa: systematic review of empirical findings. Prev Sci. 2007;8(2):141.Google Scholar
  29. 29.
    Kumar S, Rao P, Earla R, Kumar A. Drug–drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems. Expert Opin Drug Metab Toxicol. 2015;11(3):343–55.PubMedCrossRefGoogle Scholar
  30. 30.
    Hendershot CS, Stoner SA, Pantalone DW, Simoni JM. Alcohol use and antiretroviral adherence: review and meta-analysis. J Acquir Immune Defic Syndr. 2009;52(2):180.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Kalichman SC, Kalichman MO, Cherry C, Hoyt G, Washington C, Grebler T, et al. Intentional medication nonadherence because of interactive toxicity beliefs among HIV-positive active drug users. J Acquir Immune Defic Syndr. 2015;70(5):503–9.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Miguez MJ, Shor-Posner G, Morales G, Rodriguez A, Burbano X. HIV treatment in drug abusers: impact of alcohol use. Addict Biol. 2003;8(1):33–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Roux P, Carrieri MP, Villes V, Dellamonica P, Poizot-Martin I, Ravaux I, et al. The impact of methadone or buprenorphine treatment and ongoing injection on highly active antiretroviral therapy (HAART) adherence: evidence from the MANIF2000 cohort study. Addiction. 2008;103(11):1828–36.PubMedCrossRefGoogle Scholar
  34. 34.
    Soboka M, Tesfaye M, Feyissa GT, Hanlon C. Alcohol use disorders and associated factors among people living with HIV who are attending services in south west Ethiopia. BMC Res Notes. 2014;7(1):828.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Kekwaletswe CT, Morojele NK. Alcohol use, antiretroviral therapy adherence, and preferences regarding an alcohol-focused adherence intervention in patients with human immunodeficiency virus. Patient Prefer Adherence. 2014;8:401.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Pavili L, Daudin M, Moinard N, Walschaerts M, Cuzin L, Massip P, et al. Decrease of mitochondrial DNA level in sperm from patients infected with human immunodeficiency virus-1 linked to nucleoside analogue reverse transcriptase inhibitors. Fertil Steril. 2010;94(6):2151–6.PubMedCrossRefGoogle Scholar
  37. 37.
    White DJ, Mital D, Taylor S, St John JC. Sperm mitochondrial DNA deletions as a consequence of long term highly active antiretroviral therapy. AIDS. 2001;15(8):1061–2.PubMedCrossRefGoogle Scholar
  38. 38.
    Ahmad G, Moinard N, Jouanolou V, Daudin M, Gandia P, Bujan L. In vitro assessment of the adverse effects of antiretroviral drugs on the human male gamete. Toxicol In Vitro. 2011;25(2):485–91.PubMedCrossRefGoogle Scholar
  39. 39.
    Saleh RA, Agarwal A, Nada EA, El-Tonsy MH, Sharma RK, Meyer A, et al. Negative effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility. Fertil Steril. 2003;79:1597–605.PubMedCrossRefGoogle Scholar
  40. 40.
    Vicari E, Arancio A, Giuffrida V, D’Agata R, Calogero A. A case of reversible azoospermia following withdrawal from alcohol consumption. J Endocrinol Invest. 2002;25(5):473–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Ramlau-Hansen C, Toft G, Jensen MS, Strandberg-Larsen K, Hansen ML, Olsen J. Maternal alcohol consumption during pregnancy and semen quality in the male offspring: two decades of follow-up. Hum Reprod. 2010;25(9):2340–5.PubMedCrossRefGoogle Scholar
  42. 42.
    La Vignera S, Condorelli RA, Balercia G, Vicari E, Calogero AE. Does alcohol have any effect on male reproductive function? A review of literature. Asian J Androl. 2013;15(2):221.PubMedCrossRefGoogle Scholar
  43. 43.
    Rai T, Rai GS. Cigarette smoking and alcohol consumption are enemy of male fertility? A patho-radiological correlation study. Int J Res Med Sci. 2016;4(3):847–54.CrossRefGoogle Scholar
  44. 44.
    Cooper CL, Cameron DW. Effect of alcohol use and highly active antiretroviral therapy on plasma levels of hepatitis C virus (HCV) in patients coinfected with HIV and HCV. Clin Infect Dis. 2005;41(Supplement_1):S105–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Braithwaite RS, Bryant KJ. Influence of alcohol consumption on adherence to and toxicity of antiretroviral therapy and survival. Alcohol Res Health. 2010;33(3):280.PubMedPubMedCentralGoogle Scholar
  46. 46.
    McCance-Katz EF, Gruber VA, Beatty G, Lum PJ, Rainey PM. Interactions between alcohol and the antiretroviral medications ritonavir or efavirenz. J Addict Med. 2013;7(4):264.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Baum MK, Rafie C, Lai S, Sales S, Page JB, Campa A. Alcohol use accelerates HIV disease progression. AIDS Res Hum Retrovir. 2010;26(5):511–8.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Kumar S, Jin M, Ande A, Sinha N, Silverstein PS, Kumar A. Alcohol consumption effect on antiretroviral therapy and HIV-1 pathogenesis: role of cytochrome P450 isozymes. Expert Opin Drug Metab Toxicol. 2012;8(11):1363–75.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Minuesa G, Huber-Ruano I, Pastor-Anglada M, Koepsell H, Clotet B, Martinez-Picado J. Drug uptake transporters in antiretroviral therapy. Pharmacol Ther. 2011;132(3):268–79.PubMedCrossRefGoogle Scholar
  50. 50.
    Augustine LM, Markelewicz RJ, Boekelheide K, Cherrington NJ. Xenobiotic and endobiotic transporter mRNA expression in the blood-testis barrier. Drug Metab Dispos. 2005;33(1):182–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Ahn T, Yun C-H. Molecular mechanisms regulating the mitochondrial targeting of microsomal cytochrome P450 enzymes molecular mechanisms regulating the mitochondrial targeting of microsomal cytochrome P450 enzymes. Curr Drug Metab. 2010;11(10):830–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Adaramoye OA, Adesanoye O, Adewumi O, Akanni O. Studies on the toxicological effect of nevirapine, an antiretroviral drug, on the liver, kidney and testis of male Wistar rats. Hum Exp Toxicol. 2012;31(7):676–85.PubMedCrossRefGoogle Scholar
  53. 53.
    Schneider M, Neuman M, Chersich M, Parry C. Alcohol and antiretroviral therapy-A lethal cocktail. J AIDS Clin Res. 2012;2012:1–8. doi: 10.4172/2155-6113.S1-005.
  54. 54.
    Jin M, Arya P, Patel K, Singh B, Silverstein PS, Bhat HK, et al. Effect of alcohol on drug efflux protein and drug metabolic enzymes in U937 macrophages. Alcohol Clin Exp Res. 2011;35(1):132–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Walubo A. The role of cytochrome P450 in antiretroviral drug interactions. Expert Opin Drug Metab Toxicol. 2007;3(4):583–98.PubMedCrossRefGoogle Scholar
  56. 56.
    Kumar S, Earla R, Jin M, Mitra AK, Kumar A. Effect of ethanol on spectral binding, inhibition, and activity of CYP3A4 with an antiretroviral drug nelfinavir. Biochem Biophys Res Commun. 2010;402(1):163–7.PubMedCrossRefGoogle Scholar
  57. 57.
    Kumar S, Kumar A. Differential effects of ethanol on spectral binding and inhibition of cytochrome P450 3A4 with eight protease inhibitors antiretroviral drugs. Alcohol Clin Exp Res. 2011;35(12):2121–7.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Oputiri D, Elias A. Impact of co-administered lopinavir/ritonavir and sulfamethoxazole/trimethoprim on reproductive indices of male albino rats. Am J Pharmacol Sci. 2014;2(5):93–9.Google Scholar
  59. 59.
    Adaramoye OA, Akanni OO, Adewumi OM, Owumi SE. Lopinavir/ritonavir, an antiretroviral drug, lowers sperm quality and induces testicular oxidative damage in rats. Tokai J Exp Clin Med. 2015;40(2):51.PubMedGoogle Scholar
  60. 60.
    Cederbaum AI. Alcohol metabolism. Clin Liver Dis. 2012;16(4):667–85.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Stickel F, Seitz HK. Alcoholic steatohepatitis. Best Pract Res Clin Gastroenterol. 2010;24(5):683–93.PubMedCrossRefGoogle Scholar
  62. 62.
    Kim JY, Lee DY, Lee YJ, Park KJ, Kim KH, Kim JW, et al. Chronic alcohol consumption potentiates the development of diabetes through pancreatic β-cell dysfunction. World J Biol Chem. 2015;6(1):1.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Burton ME, Shaw LM, Schentag JJ, Evans WE, editors. Applied pharmacokinetics and pharmacodynamics: principles of therapeutic drug monitoring. Baltimore: Lippincott Williams & Wilkins; 2006.Google Scholar
  64. 64.
    Cottrell ML, Hadzic T, Kashuba AD. Clinical pharmacokinetic, pharmacodynamic and drug-interaction profile of the integrase inhibitor dolutegravir. Clin Pharmacokinet. 2013;52(11):981–94.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Pal D, Kwatra D, Minocha M, Paturi DK, Budda B, Mitra AK. Efflux transporters-and cytochrome P-450-mediated interactions between drugs of abuse and antiretrovirals. Life Sci. 2011;88(21):959–71.PubMedCrossRefGoogle Scholar
  66. 66.
    Vadlapatla RK, Patel M, Paturi DK, Pal D, Mitra AK. Clinically relevant drug–drug interactions between antiretrovirals and antifungals. Expert Opin Drug Metab Toxicol. 2014;10(4):561–80.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Cherry CL, Wesselingh SL. Nucleoside analogues and HIV: the combined cost to mitochondria. J Antimicrob Chemother. 2003;51(5):1091–3.PubMedCrossRefGoogle Scholar
  68. 68.
    Day BJ, Lewis W. Oxidative stress in NRTI-induced toxicity. Cardiovasc Toxicol. 2004;4(3):207–16.PubMedCrossRefGoogle Scholar
  69. 69.
    Liang Y, Li S, Chen L. The physiological role of drug transporters. Protein Cell. 2015;6(5):334–50.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Han H-K. Role of transporters in drug interactions. Arch Pharm Res. 2011;34(11):1865–77.PubMedCrossRefGoogle Scholar
  71. 71.
    Yin J, Wang J. Renal drug transporters and their significance in drug–drug interactions. Acta Pharm Sin B. 2016;6(5):363–73.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Kis O, Robillard K, Chan GN, Bendayan R. The complexities of antiretroviral drug–drug interactions: role of ABC and SLC transporters. Trends Pharmacol Sci. 2010;31(1):22–35.PubMedCrossRefGoogle Scholar
  73. 73.
    Davidson AL, Dassa E, Orelle C, Chen J. Structure, function, and evolution of bacterial ATP-binding cassette systems. Microbiol Mol Biol Rev. 2008;72(2):317–64.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Robillard KR, Hoque MT, Bendayan R. Expression of ATP-binding cassette membrane transporters in rodent and human sertoli cells: relevance to the permeability of antiretroviral therapy at the blood–testis barrier. J Pharmacol Exp Ther. 2012;340(1):96–108.PubMedCrossRefGoogle Scholar
  75. 75.
    Klein DM, Cherrington NJ. Organic and inorganic transporters of the testis: a review. Spermatogenesis. 2014;4(2):e979653.PubMedCrossRefGoogle Scholar
  76. 76.
    Klein DM, Evans KK, Hardwick RN, Dantzler WH, Wright SH, Cherrington NJ. Basolateral uptake of nucleosides by Sertoli cells is mediated primarily by equilibrative nucleoside transporter 1. J Pharmacol Exp Ther. 2013;346(1):121–9.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Huang Y, Hoque MT, Jenabian M-A, Vyboh K, Whyte S-K, Sheehan NL, et al. Antiretroviral drug transporters and metabolic enzymes in human testicular tissue: potential contribution to HIV-1 sanctuary site. J Antimicrob Chemother. 2016;71(7):1954–65. doi: 10.1093/jac/dkw046.
  78. 78.
    Su L, Mruk DD, Cheng CY. Drug transporters, the blood–testis barrier, and spermatogenesis. J Endocrinol. 2011;208(3):207–23.PubMedGoogle Scholar
  79. 79.
    Hoque MT, Kis O, De Rosa MF, Bendayan R. Raltegravir permeability across blood-tissue barriers and the potential role of drug efflux transporters. Antimicrob Agents Chemother. 2015;59(5):2572–82.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Storch CH, Theile D, Lindenmaier H, Haefeli WE, Weiss J. Comparison of the inhibitory activity of anti-HIV drugs on P-glycoprotein. Biochem Pharmacol. 2007;73(10):1573–81.PubMedCrossRefGoogle Scholar
  81. 81.
    Weiss J, Weis N, Ketabi-Kiyanvash N, Storch CH, Haefeli WE. Comparison of the induction of P-glycoprotein activity by nucleotide, nucleoside, and non-nucleoside reverse transcriptase inhibitors. Eur J Pharmacol. 2008;579(1):104–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Pyles RB, Moss JA, Baum MM. Vaginal mucosal HIV prep: fundamental insights and practical considerations. Front Clin Drug Res HIV. 2015;2:33–165.CrossRefGoogle Scholar
  83. 83.
    Srivalli KMR, Lakshmi P. Overview of P-glycoprotein inhibitors: a rational outlook. Braz J Pharm Sci. 2012;48(3):353–67.CrossRefGoogle Scholar
  84. 84.
    Ghosn J, Chaix M-L, Peytavin G, Rey E, Bresson J-L, Goujard C, et al. Penetration of enfuvirtide, tenofovir, efavirenz, and protease inhibitors in the genital tract of HIV-1-infected men. AIDS. 2004;18(14):1958–61.PubMedCrossRefGoogle Scholar
  85. 85.
    Taylor S, Pereira AS. Antiretroviral drug concentrations in semen of HIV-1 infected men. Sex Transm Infect. 2001;77(1):4–11.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Reddy YS, Gotzkowsky SK, Eron JJ, Kim JY, Fiske WD, Fiscus SA, et al. Pharmacokinetic and pharmacodynamic investigation of efavirenz in the semen and blood of human immunodeficiency virus type 1-infected men. J Infect Dis. 2002;186(9):1339–43.PubMedCrossRefGoogle Scholar
  87. 87.
    Antoniou T, Hasan S, Loutfy MR, Kovacs C, Brunetta J, Smith G, et al. Pharmacokinetics of maraviroc, raltegravir, darunavir, and etravirine in the semen of HIV-infected men. JAIDS J Acquir Immune Defic Syndr. 2013;62(2):e58–60.PubMedCrossRefGoogle Scholar
  88. 88.
    Taylor S, van Heeswijk RP, Hoetelmans RM, Workman J, Drake SM, White DJ, et al. Concentrations of nevirapine, lamivudine and stavudine in semen of HIV-1-infected men. AIDS. 2000;14(13):1979–84.PubMedCrossRefGoogle Scholar
  89. 89.
    Tiraboschi J, Niubo J, Ferrer E, Barrera-Castillo G, Rozas N, Maso-Serra M, et al. Etravirine concentrations in seminal plasma in HIV-infected patients. J Antimicrob Chemother. 2013;68(1):184–7.PubMedCrossRefGoogle Scholar
  90. 90.
    Pereira AS, Smeaton LM, Gerber JG, Acosta EP, Snyder S, Fiscus SA, et al. The pharmacokinetics of amprenavir, zidovudine, and lamivudine in the genital tracts of men infected with human immunodeficiency virus type 1 (AIDS clinical trials group study 850). J Infect Dis. 2002;186(2):198–204.PubMedCrossRefGoogle Scholar
  91. 91.
    Van Leeuwen E, ter Heine R, van der Veen F, Repping S, Beijnen JH, Prins JM. Penetration of atazanavir in seminal plasma of men infected with human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2007;51(1):335–7.PubMedCrossRefGoogle Scholar
  92. 92.
    Finch A, Pillans P. P-glycoprotein and its role in drug-drug interactions. Aust Prescr. 2014;37(4):137–9.CrossRefGoogle Scholar
  93. 93.
    Dumond JB, Reddy YS, Troiani L, Rodriguez JF, Bridges AS, Fiscus SA, et al. Differential extracellular and intracellular concentrations of zidovudine and lamivudine in semen and plasma of HIV-1-infected men. J Acquir Immune Defic Syndr. (1999). 2008;48(2):156.CrossRefGoogle Scholar
  94. 94.
    Pereira AS, Kashuba AD, Fiscus SA, Hall JE, Tidwell RR, Troiani L, et al. Nucleoside analogues achieve high concentrations in seminal plasma: relationship between drug concentration and virus burden. J Infect Dis. 1999;180(6):2039–43.PubMedCrossRefGoogle Scholar
  95. 95.
    Lowe SH, van Leeuwen E, Droste JA, van der Veen F, Reiss P, Lange JM, et al. Semen quality and drug concentrations in seminal plasma of patients using a didanosine or didanosine plus tenofovir containing antiretroviral regimen. Ther Drug Monit. 2007;29(5):566–70.PubMedCrossRefGoogle Scholar
  96. 96.
    Gurtovenko AA, Anwar J. Interaction of ethanol with biological membranes: the formation of non-bilayer structures within the membrane interior and their significance. J Phys Chem B. 2009;113(7):1983–92.PubMedCrossRefGoogle Scholar
  97. 97.
    Ingólfsson HI, Andersen OS. Alcohol’s effects on lipid bilayer properties. Biophys J. 2011;101(4):847–55. doi: 10.1016/j.bpj.2011.07.013.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Eckenhoff RG. Promiscuous ligands and attractive cavities. Mol Interv. 2001;1(5):258.PubMedGoogle Scholar
  99. 99.
    Patra M, Salonen E, Terama E, Vattulainen I, Faller R, Lee BW, et al. Under the influence of alcohol: the effect of ethanol and methanol on lipid bilayers. Biophys J. 2006;90(4):1121–35. doi: 10.1529/biophysj.105.062364.PubMedCrossRefGoogle Scholar
  100. 100.
    Dallas S, Miller DS, Bendayan R. Multidrug resistance-associated proteins: expression and function in the central nervous system. Pharmacol Rev. 2006;58(2):140–61.PubMedCrossRefGoogle Scholar
  101. 101.
    Nwogu JN, Ma Q, Babalola CP, Adedeji WA, Morse GD, Taiwo B. Pharmacokinetic, pharmacogenetic, and other factors influencing CNS penetration of antiretrovirals. AIDS Res Treat. 2016;2016:13. doi: 10.1155/2016/2587094.Google Scholar
  102. 102.
    Vasios G, Kosmidi A, Kalantzi O-I, Tsantili-Kakoulidou A, Kavantzas N, Theocharis S, et al. Simple physicochemical properties related with lipophilicity, polarity, molecular size and ionization status exert significant impact on the transfer of drugs and chemicals into human breast milk. Expert Opin Drug Metab Toxicol. 2016;12(11):1273–8.CrossRefGoogle Scholar
  103. 103.
    Kashuba ADM, Dyer JR, Kramer LM, Raasch RH, Eron JJ, Cohen MS. Antiretroviral-drug concentrations in semen: implications for sexual transmission of human immunodeficiency virus type 1. Antimicrob Agents Chemother. 1999;43(8):1817–26.PubMedPubMedCentralGoogle Scholar
  104. 104.
    Trezza CR, Kashuba AD. Pharmacokinetics of antiretrovirals in genital secretions and anatomic sites of HIV transmission: implications for HIV prevention. Clin Pharmacokinet. 2014;53(7):611–24.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Valerio C, Theocharidou E, Davenport A, Agarwal B. Human albumin solution for patients with cirrhosis and acute on chronic liver failure: beyond simple volume expansion. World J Hepatol. 2016;8(7):345–54. doi: 10.4254/wjh.v8.i7.345.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Mandrekar P, Bataller R, Tsukamoto H, Gao B. Alcoholic hepatitis: translational approaches to develop targeted therapies. Hepatology. 2016;4(64):1343–55.CrossRefGoogle Scholar
  107. 107.
    Ulldemolins M, Roberts JA, Rello J, Paterson DL, Lipman J. The effects of hypoalbuminaemia on optimizing antibacterial dosing in critically ill patients. Clin Pharmacokinet. 2011;50(2):99–110.PubMedCrossRefGoogle Scholar
  108. 108.
    Lewis J, Stine J. Review article: prescribing medications in patients with cirrhosis—a practical guide. Aliment Pharmacol Ther. 2013;37(12):1132–56.PubMedCrossRefGoogle Scholar
  109. 109.
    Johnson-Davis KL, Dasgupta A. Special issues in therapeutic drug monitoring in patients with uremia, liver disease, and in critically ill patients. In: Clarke William DA, editor. Clinical challenges in therapeutic drug monitoring: special populations, physiological conditions, and pharmacogenomics; 2016. Amsterdam, Netherlands: Elsevier. p. 245–60.  Google Scholar
  110. 110.
    Roberts JA, Pea F, Lipman J. The clinical relevance of plasma protein binding changes. Clin Pharmacokinet. 2013;52(1):1–8.PubMedCrossRefGoogle Scholar
  111. 111.
    Favorito LA, Hidalgo A Jr, Pazos HM, Costa WS, Sampaio FJ. Stereological and morphometric analysis of collagen and seminiferous tubules in testes of patients with cryptorchidism submitted or not to treatment with human chorionic gonadotrophin. Int Braz J Urol. 2005;31(6):562–8.PubMedCrossRefGoogle Scholar
  112. 112.
    Pudney J, Anderson D. Orchitis and human immunodeficiency virus type 1 infected cells in reproductive tissues from men with the acquired immune deficiency syndrome. Am J Pathol. 1991;139(1):149.PubMedPubMedCentralGoogle Scholar
  113. 113.
    Clark AM, Garland KK, Russell LD. Desert hedgehog (Dhh) gene is required in the mouse testis for formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules. Biol Reprod. 2000;63(6):1825–38.PubMedCrossRefGoogle Scholar
  114. 114.
    Azu O, Naidu E, Naidu J, Masia T, Nzemande N, Chuturgoon A, et al. Testicular histomorphologic and stereological alterations following short-term treatment with highly active antiretroviral drugs (HAART) in an experimental animal model. Andrology. 2014;2(5):772–9.PubMedCrossRefGoogle Scholar
  115. 115.
    Ogedengbe OO, Jegede AI, Onanuga IO, Offor U, Naidu EC, Peter AI, et al. Coconut oil extract mitigates testicular injury following adjuvant treatment with antiretroviral drugs. Toxicol Res. 2016;32(4):317.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Pathak A, Meena LP, Chakravarty J, Rai M, Sundar S. A pilot study to evaluate the effect of HAART on gonadal dysfunction in male HIV patients. Natl J Physiol Pharm Pharmacol. 2015;5(1):33–5. doi: 10.5455/njppp.2015.5.120720142.
  117. 117.
    Rahimipour M, Talebi AR, Anvari M, Sarcheshmeh AA, Omidi M. Effects of different doses of ethanol on sperm parameters, chromatin structure and apoptosis in adult mice. Eur J Obstet Gynecol Reprod Biol. 2013;170(2):423–8.PubMedCrossRefGoogle Scholar
  118. 118.
    Albadri CT. Alcohol consumption and its effect on testicular structure and on sperm count and motility in parent mice and their offspring. IMJM. 2013;12(1):43–8.Google Scholar
  119. 119.
    Agarwal A, Virk G, Ong C, du Plessis SS. Effect of oxidative stress on male reproduction. World J Mens Health. 2014;32(1):1–17.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Haider S, Hofmann N, Passia D. Morphological and enzyme histochemical observations on alcohol induced disturbances in testis of two patients. Andrologia. 1985;17(6):532–40.PubMedCrossRefGoogle Scholar
  121. 121.
    Alirezaei M, Kheradmand A, Heydari R, Tanideh N, Neamati S, Rashidipour M. Oleuropein protects against ethanol-induced oxidative stress and modulates sperm quality in the rat testis. Med J Nutr Metab. 2012;5(3):205–11.CrossRefGoogle Scholar
  122. 122.
    Liang Y, Yeligar SM, Brown LAS. Chronic-alcohol-abuse-induced oxidative stress in the development of acute respiratory distress syndrome. Sci World J. 2012;2012:740308. doi: 10.1100/2012/740308.
  123. 123.
    Mulligan K, Grunfeld C, Tai VW, Algren H, Pang M, Chernoff DN, et al. Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection. J Acquir Immune Defic Syndr. 2000;23(1):35–43.PubMedCrossRefGoogle Scholar
  124. 124.
    Gelato MC. Insulin and carbohydrate dysregulation. Clin Infect Dis. 2003;36(Supplement 2):S91–5.PubMedCrossRefGoogle Scholar
  125. 125.
    Brown TT, Li X, Cole SR, Kingsley LA, Palella FJ, Riddler SA, et al. Cumulative exposure to nucleoside analogue reverse transcriptase inhibitors is associated with insulin resistance markers in the Multicenter AIDS Cohort Study. AIDS. 2005;19(13):1375–83.PubMedCrossRefGoogle Scholar
  126. 126.
    Brown TT, Tassiopoulos K, Bosch RJ, Shikuma C, McComsey GA. Association between systemic inflammation and incident diabetes in HIV-infected patients after initiation of antiretroviral therapy. Diabetes Care. 2010;33(10):2244–9.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Razi M, Najafi G, Feyzi S, Karimi A, Shahmohamadloo S, Nejati V. Histological and histochemical effects of glyphosate on testicular tissue and function. Iran J Reprod Med. 2012;10(3):181.PubMedPubMedCentralGoogle Scholar
  128. 128.
    Alves M, Martins A, Rato L, Moreira P, Socorro S, Oliveira P. Molecular mechanisms beyond glucose transport in diabetes-related male infertility. BBA Mol Basis Dis. 2013;1832(5):626–35.CrossRefGoogle Scholar
  129. 129.
    Malekinejad H, Mirzakhani N, Razi M, Cheraghi H, Alizadeh A, Dardmeh F. Protective effects of melatonin and Glycyrrhiza glabra extract on ochratoxin A-induced damages on testes in mature rats. Hum Exp Toxicol. 2011;30(2):110–23.PubMedCrossRefGoogle Scholar
  130. 130.
    Bucci D, Rodriguez-Gil JE, Vallorani C, Spinaci M, Galeati G, Tamanini C. GLUTs and mammalian sperm metabolism. J Androl. 2011;32(4):348–55.PubMedCrossRefGoogle Scholar
  131. 131.
    Misro M, Ramya T. Fuel/energy sources of spermatozoa. In: Parekattil SJ, Agarwal A, editors. Male infertility. New York: Springer; 2012. p. 209–23.Google Scholar
  132. 132.
    Young L, Yu D, Bateman RM, Brock GB. Oxidative stress and antioxidant therapy: their impact in diabetes-associated erectile dysfunction. J Androl. 2004;25(5):830–6.PubMedCrossRefGoogle Scholar
  133. 133.
    La Vignera S, Calogero A, Condorelli R, Lanzafame F, Giammusso B, Vicari E. Andrological characterization of the patient with diabetes mellitus. Minerva Endocrinol. 2009;34(1):1–9.PubMedGoogle Scholar
  134. 134.
    Alves MG, Socorro S, Silva J, Barros A, Sousa M, Cavaco JE, et al. In vitro cultured human Sertoli cells secrete high amounts of acetate that is stimulated by 17β-estradiol and suppressed by insulin deprivation. BBA Mol Basis Dis. 2012;1823(8):1389–94.Google Scholar
  135. 135.
    Oliveira P, Alves M, Rato L, Laurentino S, Silva J, Sa R, et al. Effect of insulin deprivation on metabolism and metabolism-associated gene transcript levels of in vitro cultured human Sertoli cells. Biochim Biophys Acta. 2012;1820(2):84–9.PubMedCrossRefGoogle Scholar
  136. 136.
    Murata H, Hruz PW, Mueckler M. Indinavir inhibits the glucose transporter isoform Glut4 at physiologic concentrations. AIDS. 2002;16(6):859–63.PubMedCrossRefGoogle Scholar
  137. 137.
    Jover F, Cuadrado JM, Roig P, Rodríguez M, Andreu L, Merino J. Efavirenz-associated gynecomastia: report of five cases and review of the literature. Breast J. 2004;10(3):244–6.PubMedCrossRefGoogle Scholar
  138. 138.
    Araujo S, Bañón S, Machuca I, Moreno A, Pérez-Elías MJ, Casado JL. Prevalence of insulin resistance and risk of diabetes mellitus in HIV-infected patients receiving current antiretroviral drugs. Eur J Endocrinol. 2014;171(5):545–54.PubMedCrossRefGoogle Scholar
  139. 139.
    Aurpibul L, Puthanakit T, Taejaroenkul S, Sirisanthana T, Sirisanthana V. recovery from lipodystrophy in HIV-infected children after substitution of stavudine with zidovudine in a non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy. Pediatr Infect Dis J. 2012;31(4):384–8.PubMedCrossRefGoogle Scholar
  140. 140.
    da Cunha J, Maselli LMF, Stern ACB, Spada C, Bydlowski SP. Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: old and new drugs. World J Virol. 2015;4(2):56.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Johnson A. Testicular lipids. Testes. 1970;2:193–258.Google Scholar
  142. 142.
    Kastner P, Mark M, Leid M, Gansmuller A, Chin W, Grondona JM, et al. Abnormal spermatogenesis in RXR beta mutant mice. Genes Dev. 1996;10(1):80–92.PubMedCrossRefGoogle Scholar
  143. 143.
    Yildiz Y, Matern H, Thompson B, Allegood JC, Warren RL, Ramirez DM, et al. Mutation of β-glucosidase 2 causes glycolipid storage disease and impaired male fertility. J Clin Invest. 2006;116(11):2985.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Rengarajan S, Malini T, Sivakumar R, Govindarajulu P, Balasubramanian K. Effects of ethanol intoxication on LH receptors and glucose oxidation in Leydig cells of adult albino rats. Reprod Toxicol. 2003;17(6):641–8.PubMedCrossRefGoogle Scholar
  145. 145.
    Radhakrishnakartha H, Appu AP, Madambath I. Reversal of alcohol induced testicular hyperlipidemia by supplementation of ascorbic acid and its comparison with abstention in male guinea pigs. J Basic Clin Physiol. 2014;25(1):117–24.Google Scholar
  146. 146.
    Shayakhmetova GM, Bondarenko LB, Matvienko AV, Kovalenko VM. Chronic alcoholism-mediated metabolic disorders in albino rat testes. Interdiscip Toxicol. 2014;7(3):165–72.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Birkus G, Hitchcock MJ, Cihlar T. Assessment of mitochondrial toxicity in human cells treated with tenofovir: comparison with other nucleoside reverse transcriptase inhibitors. Antimicrob Agents Chemother. 2002;46(3):716–23.PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Lambert-Niclot S, Poirot C, Tubiana R, Houssaini A, Soulié C, Dominguez S, et al. Effect of antiretroviral drugs on the quality of semen. J Med Virol. 2011;83(8):1391–4.PubMedCrossRefGoogle Scholar
  149. 149.
    Dulioust E, Le Du A, Costagliola D, Guibert J, Kunstmann J-M, Heard I, et al. Semen alterations in HIV-1 infected men. Hum Reprod. 2002;17(8):2112–8.PubMedCrossRefGoogle Scholar
  150. 150.
    van Leeuwen E, Wit FW, Repping S, Schattenkerk JKME, Reiss P, van der Veen F, et al. Effects of antiretroviral therapy on semen quality. AIDS. 2008;22(5):637–42.PubMedCrossRefGoogle Scholar
  151. 151.
    Nicopoullos J, Almeida P, Vourliotis M, Gilling-Smith C. A decade of the sperm-washing programme: correlation between markers of HIV and seminal parameters. HIV Med. 2011;12(4):195–201.PubMedCrossRefGoogle Scholar
  152. 152.
    Bujan L, Sergerie M, Moinard N, Martinet S, Porte L, Massip P, et al. Decreased semen volume and spermatozoa motility in HIV-1-infected patients under antiretroviral treatment. J Androl. 2007;28(3):444–52.PubMedCrossRefGoogle Scholar
  153. 153.
    Lamb DJ. World Health Organization laboratory manual for the examination of human semen and sperm-cervical mucus interaction. J Androl. 2000;21(1):32.Google Scholar
  154. 154.
    Hamilton J, Cissen M, Brandes M, Smeenk J, De Bruin J, Kremer J, et al. Total motile sperm count: a better indicator for the severity of male factor infertility than the WHO sperm classification system. Hum Reprod. 2015;30(5):1110–21.PubMedCrossRefGoogle Scholar
  155. 155.
    Kaushik A, Saini R, Rana AC, Kaushik P. Geno-cytotoxicity study of antiretroviral drug used in HIV-therapy. J Innov Biol. 2014;2:63–7.Google Scholar
  156. 156.
    Chris-Ozoko LE, Charity AA, Ekundina VO. Histomorphological effect of zidovudine on the testes of adult male Wistar rats (Rattus norvegicus). J Basic Clin Reprod Sci. 2013;2(2):73–6.CrossRefGoogle Scholar
  157. 157.
    Neuman MG, Monteiro M, Rehm J. Drug interactions between psychoactive substances and antiretroviral therapy in individuals infected with human immunodeficiency and hepatitis viruses. Subst Use Misuse. 2006;41(10–12):1395–463.PubMedCrossRefGoogle Scholar
  158. 158.
    Martini AC, Molina RI, Estofán D, Senestrari D, de Cuneo MF, Ruiz RD. Effects of alcohol and cigarette consumption on human seminal quality. Fertil Steril. 2004;82(2):374–7.PubMedCrossRefGoogle Scholar
  159. 159.
    Muthusami K, Chinnaswamy P. Effect of chronic alcoholism on male fertility hormones and semen quality. Fertil Steril. 2005;84(4):919–24.PubMedCrossRefGoogle Scholar
  160. 160.
    Varshini J, Srinag B, Kalthur G, Krishnamurthy H, Kumar P, Rao SS, et al. Poor sperm quality and advancing age are associated with increased sperm DNA damage in infertile men. Andrologia. 2012;44(s1):642–9.PubMedCrossRefGoogle Scholar
  161. 161.
    Pajarinen J, Karhunen P. Spermatogenic arrest and ‘Sertoli cell-only’syndrome—common alcohol-induced disorders of the human testis. Int J Androl. 1994;17(6):292–9.PubMedCrossRefGoogle Scholar
  162. 162.
    Sermondade N, Elloumi H, Berthaut I, Mathieu E, Delarouzière V, Ravel C, et al. Progressive alcohol-induced sperm alterations leading to spermatogenic arrest, which was reversed after alcohol withdrawal. Reprod Biomed Online. 2010;20(3):324–7.PubMedCrossRefGoogle Scholar
  163. 163.
    Kumar P, Kumar N, Thakur DS, Patidar A. Male hypogonadism: symptoms and treatment. J Adv Pharm Technol Res. 2010;1(3):297.PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Wong N, Levy M, Stephenson I. Hypogonadism in the HIV-Infected Man. Curr Treat Options Infect Dis. 2017;9(1):104–16.PubMedPubMedCentralCrossRefGoogle Scholar
  165. 165.
    Zarotsky V, Huang M-Y, Carman W, Morgentaler A, Singhal PK, Coffin D, et al. Systematic literature review of the epidemiology of nongenetic forms of hypogonadism in adult males. J Horm. 2014;2014:190347. doi: 10.1155/2014/190347.
  166. 166.
    Lunenfeld B, Mskhalaya G, Zitzmann M, Arver S, Kalinchenko S, Tishova Y et al. Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men. The Aging Male. 2015;18(1):5–15.Google Scholar
  167. 167.
    Sexson E, Knezevich J. Male hypogonadism: a review of the disease and its treatment. US Pharm 2010;35(6):7–16.Google Scholar
  168. 168.
    McBride JA, Carson CC, Coward RM. Testosterone deficiency in the aging male. Ther Adv Urol. 2016;8(1):47–60. doi: 10.1177/1756287215612961.PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    Corradi PF, Corradi RB, Greene LW. Physiology of the hypothalamic pituitary gonadal axis in the male. Urol Clin N Am. 2016;43(2):151–62.CrossRefGoogle Scholar
  170. 170.
    Dohle G, Arver S, Bettocchi C, Jones T, Kliesch S, Punab M. Guidelines on male hypogonadism. European Association of Urology. 2015. Accessed July 2016.
  171. 171.
    Dohle GR, Arver S, Bettocchi C, Kliesch S, Punab M, de Ronde W. Guidelines on male hypogonadism. Arnhem: European Association of Urology; 2012. p. 1–28Google Scholar
  172. 172.
    Araujo AB, O’donnell AB, Brambilla DJ, Simpson WB, Longcope C, Matsumoto AM, et al. Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2004;89(12):5920–6.PubMedCrossRefGoogle Scholar
  173. 173.
    Rochira V, Zirilli L, Orlando G, Santi D, Brigante G, Diazzi C, et al. Premature decline of serum total testosterone in HIV-infected men in the HAART-era. PLoS One. 2011;6(12):e28512.PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    Dubé MP, Parker RA, Mulligan K, Tebas P, Robbins GK, Roubenoff R, et al. Effects of potent antiretroviral therapy on free testosterone levels and fat-free mass in men in a prospective, randomized trial: A5005s, a substudy of AIDS Clinical Trials Group Study 384. Clin Infect Dis. 2007;45(1):120–6.PubMedCrossRefGoogle Scholar
  175. 175.
    Lachâtre M, Pasquet A, Ajana F, Soudan B, Lion G, Bocket L, et al. HIV and hypogonadism: a new challenge for young-aged and middle-aged men on effective antiretroviral therapy. AIDS. 2017;31(3):451–3.PubMedGoogle Scholar
  176. 176.
    Gomes AC, Aragüés JM, Guerra S, Fernandes J, Mascarenhas MR. Hypogonadotropic hypogonadism in human immunodeficiency virus-infected men: uncommonly low testosterone levels. Endocrinol Diabetes Metab Case Rep. 2017;2017. doi: 10.1530/EDM-17-0104.
  177. 177.
    Pilatz A, Discher T, Lochnit G, Wolf J, Schuppe H-C, Schüttler CG, et al. Semen quality in HIV patients under stable antiretroviral therapy is impaired compared to WHO 2010 reference values and on sperm proteome level. AIDS. 2014;28(6):875–80.PubMedCrossRefGoogle Scholar
  178. 178.
    Moreno-Pérez O, Boix V, Merino E, Picó A, Reus S, Alfayate R, et al. Biological markers of fertility (inhibin-B) in HIV-infected men: influence of HIV infection and antiretroviral therapy. HIV Med. 2015;17(6):436–44Google Scholar
  179. 179.
    Weinbauer GF, Nieschlag E. The role of testosterone in spermatogenesis. In: Testosterone: action-deficiency-substitution, vol. 23. 4th ed. Cambridge: Cambridge University Press; 2012. p. 569.Google Scholar
  180. 180.
    Emanuele N, LaPaglia N, Steiner J, Kirsteins L, Emanuele M. Reversal of chronic ethanol-induced testosterone suppression in peripubertal male rats by opiate blockade. Alcohol Clin Exp Res. 1999;23(1):60–6.PubMedCrossRefGoogle Scholar
  181. 181.
    Khawcharoenporn T, Beverly ES. HIV infection and infertility. In: Genital infections and infertility. InTech. 2016. doi: 10.5772/62390
  182. 182.
    Du P, Liu A, Jiao Y, Liu C, Jiang T, Zhu W, et al. HIV RNA and proviral HIV DNA could be detected in semen although HIV RNA was undetectable in blood after 6 months of antiretroviral therapy. Microbiol Immunol. 2016;60(3):187–95.  Google Scholar
  183. 183.
    Jegede A, Offor U, Onanuga I, Naidu E, Azu O. Effect of co-administration of Hypoxis hemerocallidea extract and antiretroviral therapy (HAART) on the histomorphology and seminal parameters in Sprague Dawley rats. Andrologia. 2017;49(2):1–8. doi: 10.1111/and.12640.
  184. 184.
    Matusali G, Dereuddre-Bosquet N, Le Tortorec A, Moreau M, Satie A-P, Mahé D, et al. Detection of simian immunodeficiency virus in semen, urethra, and male reproductive organs during efficient highly active antiretroviral therapy. J Virol. 2015;89(11):5772–87.PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Oyeyipo I, Strijdom H, Skosana B, Everson F, Van der Horst G, du Plessis S, editors. Highly active antiretroviral therapy alters sperm parameters and testicular antioxidant status in lean and diet-induced obese male Wistar rats. In: Proceedings of the Physiological Society; 2015: The Physiological Society.Google Scholar
  186. 186.
    Valade E, Tréluyer J-M, Illamola SM, Bouazza N, Foissac F, Mendes MDS, et al. Emtricitabine seminal plasma and blood plasma population pharmacokinetics in HIV-infected men in the EVARIST ANRS-EP 49 study. Antimicrob Agents Chemother. 2015;59(11):6800–6.PubMedPubMedCentralCrossRefGoogle Scholar
  187. 187.
    Cristea C, Plaiasu V, Ochiana D, Neagu RD, Gherlan I, Mardarescu M. Sexual ambiguity associated with “in utero” antiretroviral exposure. Acta Endocrinol (Buc). 2011;7(4):551–60.CrossRefGoogle Scholar
  188. 188.
    Donde H. Role of ethanol as a cofactor in HAART induced hepatic steatosis and injury. Electronic Theses and Dissertations, University of Louisville; 2013.Google Scholar
  189. 189.
    Fabris P, Tositti G, Manfrin V, Giordani MT, Vaglia A, Cattelan AM, et al. Does alcohol intake affect highly active antiretroviral therapy (HAART) response in HIV-positive patients? JAIDS J Acquir Immune Defic Syndr. 2000;25(1):92–3.PubMedCrossRefGoogle Scholar
  190. 190.
    Hofny ERM, Ali MEM, Taha EA, Nafeh HM, Sayed DS, Abdel-Azeem HG, et al. Semen and hormonal parameters in men with chronic hepatitis C infection. Fertil Steril. 2011;95(8):2557–9.PubMedCrossRefGoogle Scholar
  191. 191.
    Li Y, Liu L, Wang B, Chen D, Wang J. Nonalcoholic fatty liver disease and alteration in semen quality and reproductive hormones. Eur J Gastroenterol Hepatol. 2015;27(9):1069–73.PubMedCrossRefGoogle Scholar
  192. 192.
    Dohle G, Smit M, Weber R. Androgens and male fertility. World J Urol. 2003;21(5):341–5.PubMedCrossRefGoogle Scholar
  193. 193.
    Míguez-Burbano MJ, Lewis JE, Fishman J, Asthana D, Malow RM. The influence of different types of alcoholic beverages on disrupting highly active antiretroviral treatment (HAART) outcome. Alcohol Alcohol. 2009;44(4):366–71.PubMedPubMedCentralCrossRefGoogle Scholar
  194. 194.
    McDowell JA, Chittick GE, Stevens CP, Edwards KD, Stein DS. Pharmacokinetic interaction of abacavir (1592U89) and ethanol in human immunodeficiency virus-infected adults. Antimicrob Agents Chemother. 2000;44(6):1686–90.PubMedPubMedCentralCrossRefGoogle Scholar
  195. 195.
    Whitfield RM, Bechtel LM, Starich GH. The impact of ethanol and Marinol/marijuana usage on HIV+/AIDS patients undergoing azidothymidine, azidothymidine/dideoxycytidine, or dideoxyinosine therapy. Alcohol Clin Exp Res. 1997;21(1):122–7.PubMedCrossRefGoogle Scholar
  196. 196.
    Association AD. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37(Supplement 1):S81–90.CrossRefGoogle Scholar
  197. 197.
    Samet JH, Cheng DM, Libman H, Nunes DP, Alperen JK, Saitz R. Alcohol consumption and HIV disease progression. J Acquir Immune Defic Syndr. 2007;46(2):194.PubMedPubMedCentralCrossRefGoogle Scholar
  198. 198.
    Ghebremichael M, Paintsil E, Ickovics JR, Vlahov D, Schuman P, Boland R, et al. Longitudinal association of alcohol use with HIV disease progression and psychological health of women with HIV. AIDS Care. 2009;21(7):834–41.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Discipline of Clinical Anatomy, Nelson R. Mandela School of MedicineUniversity of Kwazulu-NatalDurbanSouth Africa
  2. 2.Department of Anatomy, College of Medicine and Health SciencesAfe Babalola UniversityAdo EkitiNigeria
  3. 3.Department of AnatomySchool of Medicine, University of NamibiaWindhoekNamibia

Personalised recommendations