Generic placeholder image

Current HIV Research

Author(s): Rustin D. Crutchley*, David M. Jacobs, Joseph Gathe, Carl Mayberry, Nataliya Bulayeva, Kevin P. Rosenblatt and Kevin W. Garey

DOI: 10.2174/1570162X18666200827115615

DownloadDownload PDF Flyer Cite As
Vitamin D Assessment Over 48 Weeks in Treatment-Naive HIV Individuals Starting Lopinavir/Ritonavir Monotherapy

Page: [61 - 72] Pages: 12

  • * (Excluding Mailing and Handling)

Abstract

Background: Vitamin D deficiency is common in HIV population and has been associated with increased comorbidity risk and poor immunologic status.

Objective: To evaluate the effect of protease inhibitor lopinavir/ritonavir monotherapy on changes in serum 25-hydroxyvitamin D [25(OH)D] over 48 weeks.

Methods: Thirty-four treatment-naïve HIV individuals initiating lopinavir/ritonavir monotherapy and receiving clinical care from private practice in Houston, Texas, were included. Serum 25-hydroxyvitamin D levels from stored plasma samples collected from IMANI-2 pilot study at both baseline and 48 weeks were analyzed using LC-MS assays. Mean 25(OH)D at baseline and 48 weeks were compared using paired t-tests. Linear regression analysis was used to evaluate factors associated with changes in 25(OH)D. Logistic regression analyses were used to determine the effect of vitamin D status and covariates on CD4 cell count recovery.

Results: Mean 25(OH)D was significantly higher at 48 weeks (26.3 ng/mL (SD + 14.9); p=0.0003) compared to baseline (19.8 ng/mL (SD +12.1), with fewer individuals having vitamin D deficiency (41.2%) and severe deficiency (11.8%). Both body mass index and baseline CD4 cell count were significant independent covariates associated with 25(OH)D changes over 48 weeks. Baseline vitamin D status did not affect CD4 cell count recovery. However, in a 24-week multivariate analysis, current tobacco use was significantly associated with a decreased odds of CD4 cell count recovery (AOR 0.106, 95% CI 0.018-0.606; p=0.012).

Conclusion: Individuals treated with lopinavir/ritonavir monotherapy had significantly higher 25(OH)D after 48 weeks. Current tobacco users had significantly diminished CD4 cell count recovery after starting treatment, warranting further clinical investigation.

Keywords: Vitamin D, lopinavir/ritonavir monotherapy, HIV, tobacco, CD4, body mass index.

Graphical Abstract

[1]
Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357(3): 266-81.
[http://dx.doi.org/10.1056/NEJMra070553 ] [PMID: 17634462]
[2]
Alshahrani F, Aljohani N. Vitamin D: deficiency, sufficiency and toxicity. Nutrients 2013; 5(9): 3605-16.
[http://dx.doi.org/10.3390/nu5093605 ] [PMID: 24067388]
[3]
Anderson PH, Vitamin D, Vitamin D. Activity and metabolism in bone. Curr Osteoporos Rep 2017; 15(5): 443-9.
[http://dx.doi.org/10.1007/s11914-017-0394-8 ] [PMID: 28808890]
[4]
Bouillon R, Marcocci C, Carmeliet G, et al. Skeletal and extraskeletal actions of vitamin D: Current evidence and outstanding Questions. Endocr Rev 2019; 40(4): 1109-51.
[http://dx.doi.org/10.1210/er.2018-00126 ] [PMID: 30321335]
[5]
Dankers W, Colin EM, van Hamburg JP, Lubberts E. Vitamin D in autoimmunity: Molecular mechanisms and therapeutic potential. Front Immunol 2017; 7: 697.
[http://dx.doi.org/10.3389/fimmu.2016.00697 ] [PMID: 28163705]
[6]
DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 2004; 80(Suppl. 6): 1689S-96S.
[http://dx.doi.org/10.1093/ajcn/80.6.1689S ] [PMID: 15585789]
[7]
Melamed ML, Michos ED, Post W, Astor B. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med 2008; 168(15): 1629-37.
[http://dx.doi.org/10.1001/archinte.168.15.1629 ] [PMID: 18695076]
[8]
Nemere I, Farach-Carson MC. Membrane receptors for steroid hormones: a case for specific cell surface binding sites for vitamin D metabolites and estrogens. Biochem Biophys Res Commun 1998; 248(3): 443-9.
[http://dx.doi.org/10.1006/bbrc.1998.8492 ] [PMID: 9703943]
[9]
Norman AW. Receptors for 1alpha,25(OH)2D3: past, present, and future. J Bone Miner Res 1998; 13(9): 1360-9.
[http://dx.doi.org/10.1359/jbmr.1998.13.9.1360 ] [PMID: 9738507]
[10]
Zittermann A. Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr 2003; 89(5): 552-72.
[http://dx.doi.org/10.1079/BJN2003837 ] [PMID: 12720576]
[11]
Nieto G, Barber Y, Rubio MC, Rubio M, Fibla J. Association between AIDS disease progression rates and the Fok-I polymorphism of the VDR gene in a cohort of HIV-1 seropositive patients. J Steroid Biochem Mol Biol 2004; 89-90(1-5): 199-207.
[http://dx.doi.org/10.1016/j.jsbmb.2004.03.086 ] [PMID: 15225772]
[12]
Jiménez-Sousa MA, Martínez I, Medrano LM, Fernández-Rodríguez A, Resino S. Vitamin D in human immunodeficiency virus infection: influence on immunity and disease. Front Immunol 2018; 9: 458.
[http://dx.doi.org/10.3389/fimmu.2018.00458 ] [PMID: 29593721]
[13]
Dimitrov V, White JH. Species-specific regulation of innate immunity by vitamin D signaling. J Steroid Biochem Mol Biol 2016; 164: 246-53.
[http://dx.doi.org/10.1016/j.jsbmb.2015.09.016 ] [PMID: 26369615]
[14]
Veldman CM, Cantorna MT, DeLuca HF. Expression of 1,25-dihydroxyvitamin D(3) receptor in the immune system. Arch Biochem Biophys 2000; 374(2): 334-8.
[http://dx.doi.org/10.1006/abbi.1999.1605 ] [PMID: 10666315]
[15]
Wang Y, Zhu J, DeLuca HF. Where is the vitamin D receptor? Arch Biochem Biophys 2012; 523(1): 123-33.
[http://dx.doi.org/10.1016/j.abb.2012.04.001 ] [PMID: 22503810]
[16]
Akimbekov NS, Ortoski RA, Razzaque MS. Effects of sunlight exposure and vitamin D supplementation on HIV patients. J Steroid Biochem Mol Biol 2020. [Epub ahead of print].
[http://dx.doi.org/10.1016/j.jsbmb.2020.105664 ] [PMID: 32229174]
[17]
Mehta S, Giovannucci E, Mugusi FM, et al. Vitamin D status of HIV-infected women and its association with HIV disease progression, anemia, and mortality. PLoS One 2010; 5(1): e8770.
[http://dx.doi.org/10.1371/journal.pone.0008770 ] [PMID: 20098738]
[18]
Sudfeld CR, Wang M, Aboud S, Giovannucci EL, Mugusi FM, Fawzi WW. Vitamin D and HIV progression among Tanzanian adults initiating antiretroviral therapy. PLoS One 2012; 7(6): e40036.
[http://dx.doi.org/10.1371/journal.pone.0040036 ] [PMID: 22768212]
[19]
Viard JP, Souberbielle JC, Kirk O, et al. EuroSIDA Study Group. Vitamin D and clinical disease progression in HIV infection: results from the EuroSIDA study. AIDS 2011; 25(10): 1305-15.
[http://dx.doi.org/10.1097/QAD.0b013e328347f6f7 ] [PMID: 21522006]
[20]
Adeyemi OM, Agniel D, French AL, et al. Vitamin D deficiency in HIV-infected and HIV-uninfected women in the United States. J Acquir Immune Defic Syndr 2011; 57(3): 197-204.
[http://dx.doi.org/10.1097/QAI.0b013e31821ae418 ] [PMID: 21471818]
[21]
Kim JH, Gandhi V, Psevdos G Jr, Espinoza F, Park J, Sharp V. Evaluation of vitamin D levels among HIV-infected patients in New York City. AIDS Res Hum Retroviruses 2012; 28(3): 235-41.
[http://dx.doi.org/10.1089/aid.2011.0040 ] [PMID: 21644847]
[22]
Havers F, Smeaton L, Gupte N, et al. ACTG PEARLS; NWCS 319 Study Teams. 25-Hydroxyvitamin D insufficiency and deficiency is associated with HIV disease progression and virological failure post-antiretroviral therapy initiation in diverse multinational settings. J Infect Dis 2014; 210(2): 244-53.
[http://dx.doi.org/10.1093/infdis/jiu259 ] [PMID: 24799602]
[23]
Sudfeld CR, Giovannucci EL, Isanaka S, et al. Vitamin D status and incidence of pulmonary tuberculosis, opportunistic infections, and wasting among HIV-infected Tanzanian adults initiating antiretroviral therapy. J Infect Dis 2013; 207(3): 378-85.
[http://dx.doi.org/10.1093/infdis/jis693 ] [PMID: 23162137]
[24]
Keflie TS, Nölle N, Lambert C, Nohr D, Biesalski HK. Vitamin D deficiencies among tuberculosis patients in Africa: A systematic review. Nutrition 2015; 31(10): 1204-12.
[http://dx.doi.org/10.1016/j.nut.2015.05.003 ] [PMID: 26333888]
[25]
Sudfeld CR, Mugusi F, Aboud S, Nagu TJ, Wang M, Fawzi WW. Efficacy of vitamin D3 supplementation in reducing incidence of pulmonary tuberculosis and mortality among HIV-infected Tanzanian adults initiating antiretroviral therapy: study protocol for a randomized controlled trial. Trials 2017; 18(1): 66.
[http://dx.doi.org/10.1186/s13063-017-1819-5 ] [PMID: 28183335]
[26]
Bearden A, Abad C, Gangnon R, Sosman JM, Binkley N, Safdar N. Cross-sectional study of vitamin D levels, immunologic and virologic outcomes in HIV-infected adults. J Clin Endocrinol Metab 2013; 98(4): 1726-33.
[http://dx.doi.org/10.1210/jc.2012-4031 ] [PMID: 23457406]
[27]
Haug C, Müller F, Aukrust P, Frøland SS. Subnormal serum concentration of 1,25-vitamin D in human immunodeficiency virus infection: correlation with degree of immune deficiency and survival. J Infect Dis 1994; 169(4): 889-93.
[http://dx.doi.org/10.1093/infdis/169.4.889 ] [PMID: 7907645]
[28]
Haug CJ, Aukrust P, Haug E, Mørkrid L, Müller F, Frøland SS. Severe deficiency of 1,25-dihydroxyvitamin D3 in human immunodeficiency virus infection: association with immunological hyperactivity and only minor changes in calcium homeostasis. J Clin Endocrinol Metab 1998; 83(11): 3832-8.
[http://dx.doi.org/10.1210/jcem.83.11.5270 ] [PMID: 9814454]
[29]
Ross AC, Judd S, Kumari M, et al. Vitamin D is linked to carotid intima-media thickness and immune reconstitution in HIV-positive individuals. Antivir Ther (Lond) 2011; 16(4): 555-63.
[http://dx.doi.org/10.3851/IMP1784 ] [PMID: 21685543]
[30]
Aziz M, Livak B, Burke-Miller J, et al. Vitamin D insufficiency may impair CD4 recovery among Women’s Interagency HIV Study participants with advanced disease on HAART. AIDS 2013; 27(4): 573-8.
[http://dx.doi.org/10.1097/QAD.0b013e32835b9ba1 ] [PMID: 23095316]
[31]
Allavena C, Delpierre C, Cuzin L, et al. High frequency of vitamin D deficiency in HIV-infected patients: effects of HIV-related factors and antiretroviral drugs. J Antimicrob Chemother 2012; 67(9): 2222-30.
[http://dx.doi.org/10.1093/jac/dks176 ] [PMID: 22589455]
[32]
Crutchley RD, Gathe J Jr, Mayberry C, Trieu A, Abughosh S, Garey KW. Risk factors for vitamin D deficiency in HIV-infected patients in the south central United States. AIDS Res Hum Retroviruses 2012; 28(5): 454-9.
[http://dx.doi.org/10.1089/aid.2011.0025 ] [PMID: 21878055]
[33]
Dao CN, Patel P, Overton ET, et al. Low vitamin D among HIV-infected adults: prevalence of and risk factors for low vitamin D Levels in a cohort of HIV-infected adults and comparison to prevalence among adults in the US general population. Clin Infect Dis 2011; 52(3): 396-405.
[http://dx.doi.org/10.1093/cid/ciq158 ] [PMID: 21217186]
[34]
Mueller NJ, Fux CA, Ledergerber B, et al. Swiss HIV Cohort Study. High prevalence of severe vitamin D deficiency in combined antiretroviral therapy-naive and successfully treated Swiss HIV patients. AIDS 2010; 24(8): 1127-34.
[http://dx.doi.org/10.1097/QAD.0b013e328337b161 ] [PMID: 20168200]
[35]
Paul TV, Asha HS, Thomas N, et al. Hypovitaminosis D and bone mineral density in human immunodeficiency virus-infected men from India, with or without antiretroviral therapy. Endocr Pract 2010; 16(4): 547-53.
[http://dx.doi.org/10.4158/EP09197.OR ] [PMID: 20150027]
[36]
Rodríguez M, Daniels B, Gunawardene S, Robbins GK. High frequency of vitamin D deficiency in ambulatory HIV-Positive patients. AIDS Res Hum Retroviruses 2009; 25(1): 9-14.
[http://dx.doi.org/10.1089/aid.2008.0183 ] [PMID: 19108690]
[37]
Van Den Bout-Van Den Beukel CJ, Fievez L, Michels M, et al. Vitamin D deficiency among HIV type 1-infected individuals in the Netherlands: effects of antiretroviral therapy. AIDS Res Hum Retroviruses 2008; 24(11): 1375-82.
[http://dx.doi.org/10.1089/aid.2008.0058 ] [PMID: 18928396]
[38]
Wasserman P, Rubin DS. Highly prevalent vitamin D deficiency and insufficiency in an urban cohort of HIV-infected men under care. AIDS Patient Care STDS 2010; 24(4): 223-7.
[http://dx.doi.org/10.1089/apc.2009.0241 ] [PMID: 20377437]
[39]
Welz T, Childs K, Ibrahim F, et al. Efavirenz is associated with severe vitamin D deficiency and increased alkaline phosphatase. AIDS 2010; 24(12): 1923-8.
[http://dx.doi.org/10.1097/QAD.0b013e32833c3281 ] [PMID: 20588161]
[40]
Cervero M, Agud JL, Torres R, et al. Higher vitamin D levels in HIV-infected out-patients on treatment with boosted protease inhibitor monotherapy. HIV Med 2013; 14(9): 556-62.
[http://dx.doi.org/10.1111/hiv.12049 ] [PMID: 23738846]
[41]
Cervero M, Agud JL, García-Lacalle C, et al. Prevalence of vitamin D deficiency and its related risk factor in a Spanish cohort of adult HIV-infected patients: effects of antiretroviral therapy. AIDS Res Hum Retroviruses 2012; 28(9): 963-71.
[http://dx.doi.org/10.1089/aid.2011.0244 ] [PMID: 22242918]
[42]
Sherwood JE, Mesner OC, Weintrob AC, et al. Vitamin D deficiency and its association with low bone mineral density, HIV-related factors, hospitalization, and death in a predominantly black HIV-infected cohort. Clin Infect Dis 2012; 55(12): 1727-36.
[http://dx.doi.org/10.1093/cid/cis785 ] [PMID: 22972869]
[43]
Orkin C, Wohl DA, Williams A, Deckx H. Vitamin D deficiency in HIV: a shadow on long-term management? AIDS Rev 2014; 16(2): 59-74.
[PMID: 24759452]
[44]
Brown TT, McComsey GA. Association between initiation of antiretroviral therapy with efavirenz and decreases in 25-hydroxyvitamin D. Antivir Ther (Lond) 2010; 15(3): 425-9.
[http://dx.doi.org/10.3851/IMP1502 ] [PMID: 20516561]
[45]
Conesa-Botella A, Florence E, Lynen L, Colebunders R, Menten J, Moreno-Reyes R. Decrease of vitamin D concentration in patients with HIV infection on a non nucleoside reverse transcriptase inhibitor-containing regimen. AIDS Res Ther 2010; 7: 40.
[http://dx.doi.org/10.1186/1742-6405-7-40 ] [PMID: 21092280]
[46]
Fox J, Peters B, Prakash M, Arribas J, Hill A, Moecklinghoff C. Improvement in vitamin D deficiency following antiretroviral regime change: Results from the MONET trial. AIDS Res Hum Retroviruses 2011; 27(1): 29-34.
[http://dx.doi.org/10.1089/aid.2010.0081 ] [PMID: 20854196]
[47]
Wohl DA, Orkin C, Doroana M, et al. Change in vitamin D levels and risk of severe vitamin D deficiency over 48 weeks among HIV-1-infected, treatment-naive adults receiving rilpivirine or efavirenz in a Phase III trial (ECHO). Antivir Ther (Lond) 2014; 19(2): 191-200.
[http://dx.doi.org/10.3851/IMP2721 ] [PMID: 24430534]
[48]
Havers FP, Detrick B, Cardoso SW, et al. ACTG A5175 PEARLS and NWCS319 Study Teams. Change in vitamin d levels occurs early after antiretroviral therapy initiation and depends on treatment regimen in resource-limited settings. PLoS One 2014; 9(4): e95164.
[http://dx.doi.org/10.1371/journal.pone.0095164 ] [PMID: 24752177]
[49]
Hamzah L, Tiraboschi JM, Iveson H, et al. Effects on vitamin D, bone and the kidney of switching from fixed-dose tenofovir disoproxil fumarate/emtricitabine/efavirenz to darunavir/ritonavir monotherapy: a randomized, controlled trial (MIDAS). Antivir Ther (Lond) 2016; 21(4): 287-96.
[http://dx.doi.org/10.3851/IMP3000 ] [PMID: 26460504]
[50]
Nylén H, Habtewold A, Makonnen E, et al. Prevalence and risk factors for efavirenz-based antiretroviral treatment-associated severe vitamin D deficiency: A prospective cohort study. Medicine (Baltimore) 2016; 95(34): e4631.
[http://dx.doi.org/10.1097/MD.0000000000004631 ] [PMID: 27559961]
[51]
Koga I, Seo K, Yoshino Y, Kitazawa T, Ota Y. Increase of 25-hydroxyvitamin D levels after initiation of combination antiretroviral therapy. J Infect Chemother 2015; 21(10): 737-41.
[http://dx.doi.org/10.1016/j.jiac.2015.07.003 ] [PMID: 26298041]
[52]
Cozzolino M, Vidal M, Arcidiacono MV, Tebas P, Yarasheski KE, Dusso AS. HIV-protease inhibitors impair vitamin D bioactivation to 1,25-dihydroxyvitamin D. AIDS 2003; 17(4): 513-20.
[http://dx.doi.org/10.1097/00002030-200303070-00006 ] [PMID: 12598771]
[53]
Gathe JC Jr, Yeh R, Mayberry C, Nemecek J, Miguel B, Lipman BA, et al. Single-agent Therapy with Lopinavir/ritonavir Suppresses Plasma HIV-1 Viral Replication in HIV-1 Naive Subjects: IMANI-2 48-Week Results 4th IAS (Intl AIDS Society) Conference on HIV Pathogenesis, Treatment and Prevention; Sydney, Australia, 2007.
[54]
Dusso AS, Brown AJ, Slatopolsky E, Vitamin D, Vitamin D. Am J Physiol Renal Physiol 2005; 289(1): F8-F28.
[http://dx.doi.org/10.1152/ajprenal.00336.2004 ] [PMID: 15951480]
[55]
Nakanjako D, Kiragga AN, Musick BS, et al. Frequency and impact of suboptimal immune recovery on first-line antiretroviral therapy within the International Epidemiologic Databases to Evaluate AIDS in East Africa. AIDS 2016; 30(12): 1913-22.
[http://dx.doi.org/10.1097/QAD.0000000000001085 ] [PMID: 26959510]
[56]
Zhang L, Tin A, Brown TT, et al. Vitamin D Deficiency and Metabolism in HIV-Infected and HIV-Uninfected Men in the Multicenter AIDS Cohort Study. AIDS Res Hum Retroviruses 2017; 33(3): 261-70.
[http://dx.doi.org/10.1089/aid.2016.0144 ] [PMID: 27700140]
[57]
Branch AD, Kang M, Hollabaugh K, Wyatt CM, Chung RT, Glesby MJ. In HIV/hepatitis C virus co-infected patients, higher 25-hydroxyvitamin D concentrations were not related to hepatitis C virus treatment responses but were associated with ritonavir use. Am J Clin Nutr 2013; 98(2): 423-9.
[http://dx.doi.org/10.3945/ajcn.112.048785 ] [PMID: 23739141]
[58]
Guaraldi G, Orlando G, Zona S, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis 2011; 53(11): 1120-6.
[http://dx.doi.org/10.1093/cid/cir627 ] [PMID: 21998278]
[59]
Smit M, Brinkman K, Geerlings S, et al. ATHENA observational cohort. Future challenges for clinical care of an ageing population infected with HIV: a modelling study. Lancet Infect Dis 2015; 15(7): 810-8.
[http://dx.doi.org/10.1016/S1473-3099(15)00056-0 ] [PMID: 26070969]
[60]
Guaraldi G, Milic J, Mussini C. Aging with HIV. Curr HIV/AIDS Rep 2019; 16(6): 475-81.
[http://dx.doi.org/10.1007/s11904-019-00464-3 ] [PMID: 31823125]
[61]
Ezeamama AE, Guwatudde D, Wang M, et al. Vitamin-D deficiency impairs CD4+T-cell count recovery rate in HIV-positive adults on highly active antiretroviral therapy: A longitudinal study. Clin Nutr 2016; 35(5): 1110-7.
[http://dx.doi.org/10.1016/j.clnu.2015.08.007 ] [PMID: 26371397]
[62]
Coelho L, Cardoso SW, Luz PM, et al. Vitamin D3 supplementation in HIV infection: effectiveness and associations with antiretroviral therapy. Nutr J 2015; 14: 81.
[http://dx.doi.org/10.1186/s12937-015-0072-6 ] [PMID: 26283663]
[63]
Dougherty KA, Schall JI, Zemel BS, et al. Safety and Efficacy of High-Dose Daily Vitamin D3 Supplementation in Children and Young Adults Infected With Human Immunodeficiency Virus. J Pediatric Infect Dis Soc 2014; 3(4): 294-303.
[http://dx.doi.org/10.1093/jpids/piu012 ] [PMID: 26625449]
[64]
Steenhoff AP, Schall JI, Samuel J, et al. Vitamin D₃supplementation in Batswana children and adults with HIV: a pilot double blind randomized controlled trial. PLoS One 2015; 10(2): e0117123.
[http://dx.doi.org/10.1371/journal.pone.0117123 ] [PMID: 25706751]
[65]
Alvarez N, Aguilar-Jimenez W, Rugeles MT. The Potential Protective Role of Vitamin D Supplementation on HIV-1 Infection. Front Immunol 2019; 10: 2291.
[http://dx.doi.org/10.3389/fimmu.2019.02291 ] [PMID: 31611877]
[66]
Marshall MM, McCormack MC, Kirk GD. Effect of cigarette smoking on HIV acquisition, progression, and mortality. AIDS Educ Prev 2009; 21(Suppl. 3): 28-39.
[http://dx.doi.org/10.1521/aeap.2009.21.3_supp.28 ] [PMID: 19537952]
[67]
Helleberg M, Afzal S, Kronborg G, et al. Mortality attributable to smoking among HIV-1-infected individuals: a nationwide, population-based cohort study. Clin Infect Dis 2013; 56(5): 727-34.
[http://dx.doi.org/10.1093/cid/cis933 ] [PMID: 23254417]
[68]
Holt PG. Immune and inflammatory function in cigarette smokers. Thorax 1987; 42(4): 241-9.
[http://dx.doi.org/10.1136/thx.42.4.241 ] [PMID: 3303428]
[69]
Sopori ML, Kozak W. Immunomodulatory effects of cigarette smoke. J Neuroimmunol 1998; 83(1-2): 148-56.
[http://dx.doi.org/10.1016/S0165-5728(97)00231-2 ] [PMID: 9610683]
[70]
Valiathan R, Miguez MJ, Patel B, Arheart KL, Asthana D. Tobacco smoking increases immune activation and impairs T-cell function in HIV infected patients on antiretrovirals: a cross-sectional pilot study. PLoS One 2014; 9(5): e97698.
[http://dx.doi.org/10.1371/journal.pone.0097698 ] [PMID: 24842313]
[71]
Feldman JG, Minkoff H, Schneider MF, et al. Association of cigarette smoking with HIV prognosis among women in the HAART era: a report from the women’s interagency HIV study. Am J Public Health 2006; 96(6): 1060-5.
[http://dx.doi.org/10.2105/AJPH.2005.062745 ] [PMID: 16670229]
[72]
Winhusen T, Feaster DJ, Duan R, et al. Baseline Cigarette Smoking Status as a Predictor of Virologic Suppression and CD4 Cell Count During One-Year Follow-Up in Substance Users with Uncontrolled HIV Infection. AIDS Behav 2018; 22(6): 2026-32.
[http://dx.doi.org/10.1007/s10461-017-1928-x ] [PMID: 29030717]
[73]
Hile SJ, Feldman MB, Alexy ER, Irvine MK. Recent Tobacco Smoking is Associated with Poor HIV Medical Outcomes Among HIV-Infected Individuals in New York. AIDS Behav 2016; 20(8): 1722-9.
[http://dx.doi.org/10.1007/s10461-015-1273-x ] [PMID: 26837623]
[74]
Gazzola L, Tincati C, Bellistrì GM. Monforte Ad, Marchetti G. The absence of CD4+ T cell count recovery despite receipt of virologically suppressive highly active antiretroviral therapy: clinical risk, immunological gaps, and therapeutic options. Clin Infect Dis 2009; 48(3): 328-37.
[http://dx.doi.org/10.1086/695852 ] [PMID: 19123868]
[75]
Madu A, Ocheni S, Ibegbulam O, Aguwa E, Madu K. Pattern of CD4 T-lymphocyte Values in Cancer Patients on Cytotoxic Therapy. Ann Med Health Sci Res 2013; 3(4): 498-503.
[http://dx.doi.org/10.4103/2141-9248.122054] [PMID: 24379998]