Open Access Open Access  Restricted Access Subscription Access
What is current status of HIV infections

Comparative global epidemiology of HIV infections and status of current progress in treatment

Jyoti Singh, Bhupender S. Chhikara


Human Immunodeficiency Virus (HIV) infection has a global presence. The demographic and social impact of HIV infection vary from different parts of globe and has been a lead indicator for policy makers to design future programs towards healthy world. Here we have reviewed and represented the different aspects of global HIV epidemiology in the form of maps and graphs indicating the easy interpretation of current status of HIV infections over the world population. Further, the status of current research progress for development of drugs for HIV treatment and near future projections have been included for new treatment possibilities along with discussion about existing drugs. The newer retroviral drugs and molecules under clinical trial discussed here include NRTIs (Festinavir (BMS-986001), amdoxovir, elvucitabine, apricitabine, racivir), NNRTIs (etravirine, rilpivirine), microbicides (UC-781 (Thiocarboxanilide), TMC-120 (Dapivirine), MIV-150), protease inhibitors (darunavir, tipranavir), fusion and entry inhibitors (enfuvirtide, sifuvirtide, AMD-070, BMS-663068, Cenicriviroc, INCB-9471, BMS-488043), CCR5 inhibitors (maraviroc, vicriviroc, PRO 140, PRO 542), CD4-receptor inhibitors (ibalizumab), integrase inhibitors (raltegravir, elvitegravir, GSK-1349572), maturation inhibitors (bevirimat), LEDGINs, Gene therapy (siRNA), Vaccine development and progress in genetic and immune therapy.


HIV Infection; HIV treatment; NRTIs; NNRTIs; Protease Inhibitor; Fusion Inhibitor; Microbicides; HIV Vaccine;

Full Text:



L. Montagnier. 25 years after HIV discovery: Prospects for cure and vaccine. Virology 2010, 397, 248-54.

M.S. Gottlieb. Pneumocystis pneumonia--Los Angeles. 1981. Amer. J. Public Health 2006, 96, 980-1; discussion 82-3.

M.S. Gottlieb. Discovering AIDS. Epidemiology 1998, 9, 365-7.

J.L. Ziegler, R. Newton, E. Katongole-Mbidde, S. Mbulataiye, K. De Cock, H. Wabinga, J. Mugerwa, E. Katabiraet. al. Risk factors for Kaposi's sarcoma in HIV-positive subjects in Uganda. AIDS 1997, 11, 1619-26.

UNAIDS World AIDS Day report 2012. (Accessed on: 25 August 2013). * Provide comprehensive global data report for HIV infections

CDC. Monitoring selected national HIV prevention and care objectives by using HIV surveillance data—United States and 6 U.S. dependent areas—2010. HIV Surveillance Supplemental Report 2012;17(No. 3, part A). (Accessed on: 15 August 2013).

CDC. Estimated HIV incidence in the United States, 2007–2010. HIV Surveillance Supplemental Report 2012;17(No. 4). (Accessed on: 15 August 2013).

CDC. HIV Surveillance Report, 2010; vol. 22. (Accessed on: August 15 2013).

P. Ramachandran. Three decades of HIV/AIDS in Asia. Ind. J. Med. Res. 2013, 137, 997.

S. Lal. Current status of AIDS and HIV infection in India. J. Ind. Med. Assoc. 1994, 92, 3-4.

P. Jha, R. Kumar, A. Khera, M. Bhattacharya, P. Arora, V. Gajalakshmi, P. Bhatia, D. Kamet. al. HIV mortality and infection in India: estimates from nationally representative mortality survey of 1.1 million homes. BMJ: British Med. J. 2010, 340.

C. Shen, J. Craigo, M. Ding, Y. Chen, P. Gupta. Origin and dynamics of HIV-1 subtype C infection in India. PloS one 2011, 6, e25956.

K. Mayer. The evolving Indian AIDS epidemic: Hope & challenges of the fourth decade. Ind. J. Med. Res. 2011, 134, 739.

V. Joshua, R.S. Paranjape, R. Adhikary, J. Mahanta, P. Goswami, M.K. Manikar, G. Medhi, S.B. Akijam, B. Dzuvichu. An exploratory analysis of spatial mobility of injection drug users in the northeast region of India. Ind. J. Med. Res. 2012, 136, 54.

V. Joshua, M. Gupte, R. Adhikary, R.S. Paranjape, M.K. Manikar, G. Brahmam, J. Mahanta, B. Ramesh. Index based mapping of high risk behaviours for HIV among female sex workers in India. Ind. J. Med. Res. 2012, 136, 14.

S. Narayanan, S. Swaminathan, P. Supply, S. Shanmugam, G. Narendran, L. Hari, R. Ramachandran, C. Lochtet. al. Impact of HIV infection on the recurrence of tuberculosis in South India. J. Infect. Diseases 2010, 201, 691-703.

S. Moses, B.M. Ramesh, N.J. Nagelkerke, A. Khera, S. Isac, P. Bhattacharjee, V. Gurnani, R. Washingtonet. al. Impact of an intensive HIV prevention programme for female sex workers on HIV prevalence among antenatal clinic attenders in Karnataka state, south India: an ecological analysis. AIDS 2008, 22, S101-S08.

V.V. Patel, K.H. Mayer, H.J. Makadon. Men who have sex with men in India: A diverse population in need of medical attention. Ind. J. Med. Res. 2012, 136, 563.

M. Fearon. The laboratory diagnosis of HIV infections. Can. J. Infect. Diseases & Med. Microbiol. 2005, 16, 26-30.

M. Zhang, J. Versalovic. HIV update. Diagnostic tests and markers of disease progression and response to therapy. Amer. J. Clin. Pathol. 2002, 118 Suppl, S26-32.

M.S. Hirsch, F. Brun-Vezinet, B. Clotet, B. Conway, D.R. Kuritzkes, R.T. D'Aquila, L.M. Demeter, S.M. Hammeret. al. Antiretroviral drug resistance testing in adults infected with human immunodeficiency virus type 1: 2003 recommendations of an International AIDS Society-USA Panel. Clin. Infect. Diseases 2003, 37, 113-28.

S. Cox, J. Southby. Apricitabine--a novel nucleoside reverse transcriptase inhibitor for the treatment of HIV infection that is refractory to existing drugs. Expert Opin. Investigat. Drugs 2009, 18, 199-209.

M.A. Wainberg, P. Cahn, R.C. Bethell, J. Sawyer, S. Cox. Apricitabine: a novel deoxycytidine analogue nucleoside reverse transcriptase inhibitor for the treatment of nucleoside-resistant HIV infection. Antiviral Chem. & Chemother. 2007, 18, 61-70.

B.S. Chhikara, K. Parang. Development of cytarabine prodrugs and delivery systems for leukemia treatment. Expert Opin. Drug Deliv. 2010, 7, 1399-414.

B.S. Chhikara, D. Mandal, K. Parang. Synthesis and evaluation of fatty acyl ester derivatives of cytarabine as anti-leukemia agents. Europ. J. Med. Chem. 2010, 45, 4601-08.

B.S. Chhikara, D. Mandal, K. Parang. Synthesis, anticancer activities, and cellular uptake studies of lipophilic derivatives of doxorubicin succinate. J. Med. Chem. 2012, 55, 1500-10.

J.A. Arnott, S.L. Planey. The influence of lipophilicity in drug discovery and design. Expert Opin. Drug Discov. 2012, 7, 863-75.

C.A. Langner, J.K. Lodge, S.J. Travis, J.E. Caldwell, T. Lu, Q. Li, M.L. Bryant, B. Devadaset. al. 4-oxatetradecanoic acid is fungicidal for Cryptococcus neoformans and inhibits replication of human immunodeficiency virus I. J. Biol. Chem. 1992, 267, 17159-69.

T.A. Farazi, G. Waksman, J.I. Gordon. The biology and enzymology of protein N-myristoylation. J. Biol. Chem. 2001, 276, 39501-4.

M. Bryant, C. McWherter, N. Kishore, G. Gokel, J. Gordon. MyristolyCoA:protein N-myristoyltransferase as a therapeutic target for inhibiting replication of human immunodeficiency virus-1. Perspect. Drug Discov. Design 1993, 1, 193-209.

N. Takamune, H. Hamada, S. Misumi, S. Shoji. Novel strategy for anti-HIV-1 action: selective cytotoxic effect of N-myristoyltransferase inhibitor on HIV-1-infected cells. FEBS Lett. 2002, 527, 138-42.

K. Parang, L.I. Wiebe, E.E. Knaus, J.S. Huang, D.L. Tyrrell, F. Csizmadia. In vitro antiviral activities of myristic acid analogs against human immunodeficiency and hepatitis B viruses. Antiviral Res. 1997, 34, 75-90.

B.S. Chhikara, R. Tiwari, K. Parang. N-Myristoylglutamic Acid Derivative of 3'-Fluoro-3'-Deoxythymidine as an Organogel. Tetrahedron Lett 2012, 53, 5335-37.

H.K. Agarwal, K.W. Buckheit, R.W. Buckheit, Jr., K. Parang. Synthesis and anti-HIV activities of symmetrical dicarboxylate esters of dinucleoside reverse transcriptase inhibitors. Bioorg. Med. Chem. Lett. 2012, 22, 5451-4.

H.K. Agarwal, B.S. Chhikara, M.J. Hanley, G. Ye, G.F. Doncel, K. Parang. Synthesis and biological evaluation of fatty acyl ester derivatives of (-)-2',3'-dideoxy-3'-thiacytidine. J. Med. Chem. 2012, 55, 4861-71.

H.K. Agarwal, B.S. Chhikara, M. Quiterio, G.F. Doncel, K. Parang. Synthesis and anti-HIV activities of glutamate and peptide conjugates of nucleoside reverse transcriptase inhibitors. J. Med. Chem. 2012, 55, 2672-87.

H.K. Agarwal, B.S. Chhikara, S. Bhavaraju, D. Mandal, G.F. Doncel, K. Parang. Emtricitabine prodrugs with improved anti-HIV activity and cellular uptake. Mol. Pharmac. 2013, 10, 467-76.

L. Cotte, P. Dellamonica, F. Raffi, Y. Yazdanpanah, J.M. Molina, F. Boue, Y. Urata, H.P. Chanet. al. Randomized placebo-controlled study of the safety, tolerability, antiviral activity, and pharmacokinetics of 10-day monotherapy with BMS-986001, a novel HIV NRTI, in treatment-experienced HIV-1-infected subjects. J. Acquir. Immune Defic. Syndr. 2013, 63, 346-54.

M.S. Saag. New and investigational antiretroviral drugs for HIV infection: mechanisms of action and early research findings. Topics Antiviral Med. 2012, 20, 162-7.

L. Zhou, S.J. Coats, H. Zhang, S. Junxing, D.R. Bobeck, R.F. Schinazi. Scaleable processes for the synthesis of (-)-beta-D-2,6-diaminopurine dioxolane (Amdoxovir, DAPD) and (-)-beta-D-2-aminopurine dioxolane (APD). Tetrahedron 2012, 68, 5738-43.

R.L. Murphy, N.M. Kivel, C. Zala, C. Ochoa, P. Tharnish, J. Mathew, M.L. Pascual, R.F. Schinazi. Antiviral activity and tolerability of amdoxovir with zidovudine in a randomized double-blind placebo-controlled study in HIV-1-infected individuals. Antiviral Ther. 2010, 15, 185-92.

J. Shi, J.J. McAtee, S. Schlueter Wirtz, P. Tharnish, A. Juodawlkis, D.C. Liotta, R.F. Schinazi. Synthesis and biological evaluation of 2',3'-didehydro-2',3'- dideoxy-5-fluorocytidine (D4FC) analogues: discovery of carbocyclic nucleoside triphosphates with potent inhibitory activity against HIV-1 reverse transcriptase. J. Med. Chem. 1999, 42, 859-67.

M. Desai, G. Iyer, R.K. Dikshit. Antiretroviral drugs: critical issues and recent advances. Ind. J. Pharmacol. 2012, 44, 288-98.

R.K. Ghosh, S.M. Ghosh, S. Chawla. Recent advances in antiretroviral drugs. Expert Opin. Pharmacother. 2011, 12, 31-46.

S. Martins, M.J. Ramos, P.A. Fernandes. The current status of the NNRTI family of antiretrovirals used in the HAART regime against HIV infection. Current Med. Chem. 2008, 15, 1083-95.

A. Verma, S.K. Saraf. 4-thiazolidinone--a biologically active scaffold. Eur. J. Med. Chem. 2008, 43, 897-905.

V. Ravichandran, B.R. Prashantha Kumar, S. Sankar, R.K. Agrawal. Predicting anti-HIV activity of 1,3,4-thiazolidinone derivatives: 3D-QSAR approach. Eur. J. Med. Chem. 2009, 44, 1180-7.

R.K. Rawal, A. Kumar, M.I. Siddiqi, S.B. Katti. Molecular docking studies on 4-thiazolidinones as HIV-1 RT inhibitors. J. Mol. Model. 2007, 13, 155-61.

S. Wildum, D. Paulsen, K. Thede, H. Ruebsamen-Schaeff, H. Zimmermann. In Vitro and In Vivo Activities of AIC292, a Novel HIV-1 Nonnucleoside Reverse Transcriptase Inhibitor. Antimicrobial Agents Chemother. 2013.

C.M. Bailey, T.J. Sullivan, P. Iyidogan, J. Tirado-Rives, R. Chung, J. Ruiz-Caro, E. Mohamed, W. Jorgensenet. al. Bifunctional inhibition of human immunodeficiency virus type 1 reverse transcriptase: mechanism and proof-of-concept as a novel therapeutic design strategy. J. Med. Chem. 2013, 56, 3959-68.

A. Li, Y. Ouyang, Z. Wang, Y. Cao, X. Liu, L. Ran, C. Li, L. Liet. al. Novel pyridinone derivatives as non-nucleoside reverse transcriptase inhibitors (NNRTIs) with high potency against NNRTI-resistant HIV-1 strains. J. Med. Chem. 2013, 56, 3593-608.

M.S. Novikov, V.T. Valuev-Elliston, D.A. Babkov, M.P. Paramonova, A.V. Ivanov, S.A. Gavryushov, A.L. Khandazhinskaya, S.N. Kochetkovet. al. N1,N3-disubstituted uracils as nonnucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg. Med. Chem. 2013, 21, 1150-8.

M. Venkatraj, K.K. Arien, J. Heeres, B. Dirie, J. Joossens, S. Van Goethem, P. Van der Veken, J. Michielset. al. Novel diarylpyridinones, diarylpyridazinones and diarylphthalazinones as potential HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs). Bioorg. Med. Chem. 2011, 19, 5924-34.

P. Vernazza, C. Wang, A. Pozniak, E. Weil, P. Pulik, D.A. Cooper, R. Kaplan, A. Lazzarinet. al. Efficacy and safety of lersivirine (UK-453,061) versus efavirenz in antiretroviral treatment-naive HIV-1-infected patients: week 48 primary analysis results from an ongoing, multicenter, randomized, double-blind, phase IIb trial. J. Acquir. Immune Defic. Syndr. 2013, 62, 171-9.

R. Pauwels, E. De Clercq. Development of vaginal microbicides for the prevention of heterosexual transmission of HIV. J. Acquir. Immune Defic. Syndr. 1996, 11, 211-21.

K. Malcolm, D. Woolfson, C. Toner, D. Lowry. Vaginal microbicides for the prevention of HIV transmission. Biotechnol. Genetic Engin. Rev. 2004, 21, 81-121.

J. Weber, K. Desai, J. Darbyshire. The development of vaginal microbicides for the prevention of HIV transmission. PLoS Medic. 2005, 2, e142.

J. Nuttall. Microbicides in the prevention of HIV infection: current status and future directions. Drugs 2010, 70, 1231-43.

S. Naswa, Y.S. Marfatia, T.L. Prasad. Microbicides and HIV: A Review and an update. Ind. J. Sexual. Transm. Diseases 2012, 33, 81-90.

G. Doncel, C. Mauck. Vaginal microbicides: a novel approach to preventing sexual transmission of HIV. Current HIV/AIDS Reports 2004, 1, 25-32.

M.R. Boyd, K.R. Gustafson, J.B. McMahon, R.H. Shoemaker, B.R. O'Keefe, T. Mori, R.J. Gulakowski, L. Wuet. al. Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development. Antimicrobial Agents Chemother. 1997, 41, 1521-30.

S. Harman, C. Herrera, N. Armanasco, J. Nuttall, R.J. Shattock. Preclinical evaluation of the HIV-1 fusion inhibitor L'644 as a potential candidate microbicide. Antimicrobial Agents Chemother. 2012, 56, 2347-56.

O.J. D'Cruz, F.M. Uckun. Clinical development of microbicides for the prevention of HIV infection. Current Pharmac. Design 2004, 10, 315-36.

N.S. Joglekar, S.N. Joshi, S.S. Deshpande, A.N. Parkhe, U.R. Katti, S.M. Mehendale. Acceptability and adherence: findings from a Phase II study of a candidate vaginal microbicide, 'Praneem polyherbal tablet', in Pune, India. Transactions Royal Soc Trop Med Hygiene 2010, 104, 412-5.

S.N. Joshi, S. Dutta, B.K. Kumar, U. Katti, S. Kulkarni, A. Risbud, S. Mehendale. Expanded safety study of Praneem polyherbal vaginal tablet among HIV-uninfected women in Pune, India: a phase II clinical trial report. Sexually Transmitted Infect 2008, 84, 343-7.

J.J. Tan, X.T. Ma, C. Liu, X.Y. Zhang, C.X. Wang. The current status and challenges in the development of fusion inhibitors as therapeutics for HIV-1 infection. Current Pharmac. Design 2013, 19, 1810-7.

D. Eggink, B. Berkhout, R.W. Sanders. Inhibition of HIV-1 by fusion inhibitors. Current Pharmac. Design 2010, 16, 3716-28.

X. Yao, H. Chong, C. Zhang, S. Waltersperger, M. Wang, S. Cui, Y. He. Broad antiviral activity and crystal structure of HIV-1 fusion inhibitor sifuvirtide. J. Biol. Chem. 2012, 287, 6788-96.

L. Li, Y. Ben, S. Yuan, S. Jiang, J. Xu, X. Zhang. Efficacy, stability, and biosafety of sifuvirtide gel as a microbicide candidate against HIV-1. PloS one 2012, 7, 16.

G. Zhou, S. Chu. Discovery of Small Molecule Fusion Inhibitors Targeting HIV-1 gp41. Current Pharmac. Design 2013, 19, 1818-26.

A. Ashkenazi, M. Viard, L. Unger, R. Blumenthal, Y. Shai. Sphingopeptides: dihydrosphingosine-based fusion inhibitors against wild-type and enfuvirtide-resistant HIV-1. FASEB J. 2012, 26, 4628-36.

H. Chong, X. Yao, Z. Qiu, J. Sun, M. Zhang, S. Waltersperger, M. Wang, S.-L. Liuet. al. Short-peptide fusion inhibitors with high potency against wild-type and enfuvirtide-resistant HIV-1. FASEB J. 2013, 27, 1203-13.

S. Abel, D.J. Back, M. Vourvahis. Maraviroc: pharmacokinetics and drug interactions. Antiviral Ther. 2009, 14, 607-18.

S.S. Lieberman-Blum, H.B. Fung, J.C. Bandres. Maraviroc: a CCR5-receptor antagonist for the treatment of HIV-1 infection. Clinical Therapeut. 2008, 30, 1228-50.

T.J. Henrich, D.R. Kuritzkes. HIV-1 entry inhibitors: recent development and clinical use. Curr. Opin. Virol. 2013, 3, 51-7.

A. Wilkin, J. Feinberg. New targets in antiretroviral therapy 2006. Curr. Opin. HIV AIDS 2006, 1, 437-41.

R.E. Nettles, D. Schurmann, L. Zhu, M. Stonier, S.P. Huang, I. Chang, C. Chien, M. Krystalet. al. Pharmacodynamics, safety, and pharmacokinetics of BMS-663068, an oral HIV-1 attachment inhibitor in HIV-1-infected subjects. J. Infect. Diseases 2012, 206, 1002-11.

O.M. Klibanov, S.H. Williams, C.A. Iler. Cenicriviroc, an orally active CCR5 antagonist for the potential treatment of HIV infection. Curr. Opin. Investig. Drugs 2010, 11, 940-50.

N. Shin, K. Solomon, N. Zhou, K.H. Wang, V. Garlapati, B. Thomas, Y. Li, M. Covingtonet. al. Identification and characterization of INCB9471, an allosteric noncompetitive small-molecule antagonist of C-C chemokine receptor 5 with potent inhibitory activity against monocyte migration and HIV-1 infection. J. Pharmacol. Exp. Therapeut. 2011, 338, 228-39.

C.S. Pace, M.W. Fordyce, D. Franco, C.Y. Kao, M.S. Seaman, D.D. Ho. Anti-CD4 monoclonal antibody ibalizumab exhibits breadth and potency against HIV-1, with natural resistance mediated by the loss of a V5 glycan in envelope. J. Acquir. Immune Defic. Syndr. 2013, 62, 1-9.

A.R. Tenorio. The monoclonal CCR5 antibody PRO-140: the promise of once-weekly HIV therapy. Curr. HIV/AIDS Rep. 2011, 8, 1-3.

J.M. Jacobson, J.P. Lalezari, M.A. Thompson, C.J. Fichtenbaum, M.S. Saag, B.S. Zingman, P. D'Ambrosio, N. Stambleret. al. Phase 2a study of the CCR5 monoclonal antibody PRO 140 administered intravenously to HIV-infected adults. Antimicrobial Agents Chemother. 2010, 54, 4137-42.

J.M. Jacobson, R.J. Israel, I. Lowy, N.A. Ostrow, L.S. Vassilatos, M. Barish, D.N. Tran, B.M. Sullivanet. al. Treatment of advanced human immunodeficiency virus type 1 disease with the viral entry inhibitor PRO 542. Antimicrobial Agents Chemother. 2004, 48, 423-9.

P. McNicholas, R.A. Vilchez, W. Greaves, S. Kumar, C. Onyebuchi, T. Black, J.M. Strizki. Detection of HIV-1 CXCR4 tropism and resistance in treatment experienced subjects receiving CCR5 antagonist-Vicriviroc. J. Clin Virol. 2012, 55, 134-9.

G.J. Hanna, J. Lalezari, J.A. Hellinger, D.A. Wohl, R. Nettles, A. Persson, M. Krystal, P. Linet. al. Antiviral activity, pharmacokinetics, and safety of BMS-488043, a novel oral small-molecule HIV-1 attachment inhibitor, in HIV-1-infected subjects. Antimicrobial Agents Chemother. 2011, 55, 722-8.

N. Zhou, B. Nowicka-Sans, S. Zhang, L. Fan, J. Fang, H. Fang, Y.F. Gong, B. Eggerset. al. In vivo patterns of resistance to the HIV attachment inhibitor BMS-488043. Antimicrobial Agents Chemother. 2011, 55, 729-37.

L.T. Da, J.M. Quan, Y.D. Wu. Understanding the binding mode and function of BMS-488043 against HIV-1 viral entry. Proteins 2011, 79, 1810-9.

R.M. Gulick, Z. Su, C. Flexner, M.D. Hughes, P.R. Skolnik, T.J. Wilkin, R. Gross, A. Krambrinket. al. Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-Infected, treatment-experienced patients: AIDS clinical trials group 5211. J. Infect. Diseases 2007, 196, 304-12.

V. Miller. International perspectives on antiretroviral resistance. Resistance to protease inhibitors. J Acquir. Immune Defic. Syndr. 2001, 26 Suppl 1, S34-50.

E.J. Arts, D.J. Hazuda. HIV-1 antiretroviral drug therapy. Cold Spring Harbor Persp. Med. 2012, 2, a007161.

R.W. Shafer, K. Dupnik, M.A. Winters, S.H. Eshleman. A guide to HIV-1 reverse transcriptase and protease sequencing for drug resistance studies. HIV Sequence Compend. 2001, 2001, 1.

A. Molla, M. Korneyeva, Q. Gao, S. Vasavanonda, P.J. Schipper, H.M. Mo, M. Markowitz, T. Chernyavskiyet. al. Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Nat. Med. 1996, 2, 760-6.

L. Doyon, G. Croteau, D. Thibeault, F. Poulin, L. Pilote, D. Lamarre. Second locus involved in human immunodeficiency virus type 1 resistance to protease inhibitors. J. Virol. 1996, 70, 3763-9.

Y.M. Zhang, H. Imamichi, T. Imamichi, H.C. Lane, J. Falloon, M.B. Vasudevachari, N.P. Salzman. Drug resistance during indinavir therapy is caused by mutations in the protease gene and in its Gag substrate cleavage sites. J. Virol. 1997, 71, 6662-70.

G.M. Lucas. Antiretroviral adherence, drug resistance, viral fitness and HIV disease progression: a tangled web is woven. J. Antimicr. Chemother. 2005, 55, 413-6.

F. Clavel, E. Race, F. Mammano. HIV drug resistance and viral fitness. Adv Pharmacol 2000, 49, 41-66.

S.K. Lee, M. Potempa, R. Swanstrom. The choreography of HIV-1 proteolytic processing and virion assembly. J. Biol. Chem. 2012, 287, 40867-74.

L. Chen, C. Lee. Distinguishing HIV-1 drug resistance, accessory, and viral fitness mutations using conditional selection pressure analysis of treated versus untreated patient samples. Biol. Direct 2006, 1, 14.

A. De Luca In Antiretroviral Resistance in Clinical Practice, A.M. Geretti, Ed. London, 2006.

M. Nijhuis, S. Deeks, C. Boucher. Implications of antiretroviral resistance on viral fitness. Curr. Opin. Infect. Diseases 2001, 14, 23-8.

B. Berkhout. HIV-1 evolution under pressure of protease inhibitors: climbing the stairs of viral fitness. J. Biomed. Sci. 1999, 6, 298-305.

A.S. Espeseth, P. Felock, A. Wolfe, M. Witmer, J. Grobler, N. Anthony, M. Egbertson, J.Y. Melamedet. al. HIV-1 integrase inhibitors that compete with the target DNA substrate define a unique strand transfer conformation for integrase. Proc. Nat. Acad. Sci. 2000, 97, 11244-9.

D.J. Hazuda, N.J. Anthony, R.P. Gomez, S.M. Jolly, J.S. Wai, L. Zhuang, T.E. Fisher, M. Embreyet. al. A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase. Proc. Nat. Acad. Sci. 2004, 101, 11233-8.

F. Scopelliti, M. Pollicita, F. Ceccherini-Silberstein, F. Di Santo, M. Surdo, S. Aquaro, C.F. Perno. Comparative antiviral activity of integrase inhibitors in human monocyte-derived macrophages and lymphocytes. Antiviral Res. 2011, 92, 255-61.

D.J. McColl, X. Chen. Strand transfer inhibitors of HIV-1 integrase: bringing IN a new era of antiretroviral therapy. Antiviral Res. 2010, 85, 101-18.

J.A. Grobler, K. Stillmock, B. Hu, M. Witmer, P. Felock, A.S. Espeseth, A. Wolfe, M. Egbertsonet. al. Diketo acid inhibitor mechanism and HIV-1 integrase: implications for metal binding in the active site of phosphotransferase enzymes. Proc. Nat. Acad. Sci. 2002, 99, 6661-6.

S. Hare, A.M. Vos, R.F. Clayton, J.W. Thuring, M.D. Cummings, P. Cherepanov. Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance. Proc. Nat. Acad. Sci. 2010, 107, 20057-62.

I.R. Singh, J.E. Gorzynski, D. Drobysheva, L. Bassit, R.F. Schinazi. Raltegravir is a potent inhibitor of XMRV, a virus implicated in prostate cancer and chronic fatigue syndrome. PloS one 2010, 5, e9948.

K. Shimura, E. Kodama, Y. Sakagami, Y. Matsuzaki, W. Watanabe, K. Yamataka, Y. Watanabe, Y. Ohataet. al. Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137). J. Virol. 2008, 82, 764-74.

J. Marinello, C. Marchand, B.T. Mott, A. Bain, C.J. Thomas, Y. Pommier. Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Biochem. 2008, 47, 9345-54.

S. Fransen, S. Gupta, R. Danovich, D. Hazuda, M. Miller, M. Witmer, C.J. Petropoulos, W. Huang. Loss of raltegravir susceptibility by human immunodeficiency virus type 1 is conferred via multiple nonoverlapping genetic pathways. J. Virol. 2009, 83, 11440-6.

O. Goethals, R. Clayton, M. Van Ginderen, I. Vereycken, E. Wagemans, P. Geluykens, K. Dockx, R. Strijboset. al. Resistance mutations in human immunodeficiency virus type 1 integrase selected with elvitegravir confer reduced susceptibility to a wide range of integrase inhibitors. J. Virol. 2008, 82, 10366-74.

V.N. Telvekar, K.N. Patel. Pharmacophore development and docking studies of the hiv-1 integrase inhibitors derived from N-methylpyrimidones, Dihydroxypyrimidines, and bicyclic pyrimidinones. Chem. Biol. Drug Design 2011, 78, 150-60.

W. Nomura, H. Aikawa, N. Ohashi, E. Urano, M. Metifiot, M. Fujino, K. Maddali, T. Ozakiet. al. Cell-Permeable Stapled Peptides Based on HIV-1 Integrase Inhibitors Derived from HIV-1 Gene Products. ACS Chem. Biol. 2013.

V.R. de Soultrait, P.Y. Lozach, R. Altmeyer, L. Tarrago-Litvak, S. Litvak, M.L. Andreola. DNA aptamers derived from HIV-1 RNase H inhibitors are strong anti-integrase agents. J. Mol. Biol. 2002, 324, 195-203.

F. Christ, Z. Debyser. The LEDGF/p75 integrase interaction, a novel target for anti-HIV therapy. Virology 2013, 435, 102-9.

L. De Luca, S. Ferro, F. Morreale, A. Chimirri. Inhibition of the interaction between HIV-1 integrase and its cofactor LEDGF/p75: a promising approach in anti-retroviral therapy. Mini Rev. Med. Chem. 2011, 11, 714-27.

C. Tintori, N. Veljkovic, V. Veljkovic, M. Botta. Computational studies of the interaction between the HIV-1 integrase tetramer and the cofactor LEDGF/p75: insights from molecular dynamics simulations and the informational spectrum method. Proteins 2010, 78, 3396-408.

L. De Luca, S. Ferro, R. Gitto, M.L. Barreca, S. Agnello, F. Christ, Z. Debyser, A. Chimirri. Small molecules targeting the interaction between HIV-1 integrase and LEDGF/p75 cofactor. Bioorg. Med. Chem. 2010, 18, 7515-21.

E. Serrao, B. Debnath, H. Otake, Y. Kuang, F. Christ, Z. Debyser, N. Neamati. Fragment-based discovery of 8-hydroxyquinoline inhibitors of the HIV-1 integrase-lens epithelium-derived growth factor/p75 (IN-LEDGF/p75) interaction. J. Med. Chem. 2013, 56, 2311-22.

Z. Hayouka, M. Hurevich, A. Levin, H. Benyamini, A. Iosub, M. Maes, D.E. Shalev, A. Loyteret. al. Cyclic peptide inhibitors of HIV-1 integrase derived from the LEDGF/p75 protein. Bioorg. Med. Chem. 2010, 18, 8388-95.

D.E. Martin, K. Salzwedel, G.P. Allaway. Bevirimat: a novel maturation inhibitor for the treatment of HIV-1 infection. Antiviral Chem. Chemother. 2008, 19, 107-13.

C.S. Adamson, M. Sakalian, K. Salzwedel, E.O. Freed. Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat. Retrovirol. 2010, 7, 36.

Z. Dang, P. Ho, L. Zhu, K. Qian, K.H. Lee, L. Huang, C.H. Chen. New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. J. Med. Chem. 2013, 56, 2029-37.

P. Coric, S. Turcaud, F. Souquet, L. Briant, B. Gay, J. Royer, N. Chazal, S. Bouaziz. Synthesis and biological evaluation of a new derivative of bevirimat that targets the Gag CA-SP1 cleavage site. Eur. J. Med. Chem. 2013, 62, 453-65.

A. Mescalchin, T. Restle. Oligomeric nucleic acids as antivirals. Molecules 2011, 16, 1271-96.

A. Ambesajir, A. Kaushik, J.J. Kaushik, S.T. Petros. RNA interference: A futuristic tool and its therapeutic applications. Saudi J. Biol. Sci. 2012, 19, 395-403.

P.J. Joshi, T.S. Fisher, V.R. Prasad. Anti-HIV inhibitors based on nucleic acids: emergence of aptamers as potent antivirals. Curr. Drug Targets Infect. Disord. 2003, 3, 383-400.

J. Chung, D.L. DiGiusto, J.J. Rossi. Combinatorial RNA-based gene therapy for the treatment of HIV/AIDS. Expert Opin. Biol. Ther. 2013, 13, 437-45.

C. Lavigne, K. Slater, N. Gajanayaka, C. Duguay, E. Arnau Peyrotte, G. Fortier, M. Simard, A.J. Kellet. al. Influence of lipoplex surface charge on siRNA delivery: application to the in vitro downregulation of CXCR4 HIV-1 co-receptor. Expert Opin. Biol. Ther. 2013, 13, 973-85.

Z. Klase, L. Houzet, K.T. Jeang. MicroRNAs and HIV-1: complex interactions. J. Biol. Chem. 2012, 287, 40884-90.

C. Wang, Q. Zhou. Systemic delivery of siRNA: challenging but promising. Recent Patents Drug Del. Formul. 2012, 6, 19-30.

J. Zhou, J.J. Rossi. Therapeutic potential of aptamer-siRNA conjugates for treatment of HIV-1. BioDrugs: Clin. Immunother. Biopharm. Gene Ther. 2012, 26, 393-400.

B.S. Chhikara, S.K. Misra, S. Bhattacharya. CNT loading into cationic cholesterol suspensions show improved DNA binding and serum stability and ability to internalize into cancer cells. Nanotechnol. 2012, 23, 065101.

A. Pal, B.S. Chhikara, A. Govindaraj, S. Bhattacharya, C.N.R. Rao. Synthesis and properties of novel nanocomposites made of single-walled carbon nanotubes and low molecular mass organogels and their thermo-responsive behavior triggered by near IR radiation. J. Mater. Chem. 2008, 18, 2593-600.

S. Yang, Y. Chen, R. Ahmadie, E.A. Ho. Advancements in the field of intravaginal siRNA delivery. J. Control. Rel. 2013, 167, 29-39.

P.D. Kwong, J.R. Mascola, G.J. Nabel. Broadly neutralizing antibodies and the search for an HIV-1 vaccine: the end of the beginning. Nat. Rev. Immunol. 2013, 13, 693-701.

P.D. Kwong, J.R. Mascola, G.J. Nabel. Rational design of vaccines to elicit broadly neutralizing antibodies to HIV-1. Cold Spring Harbor Persp. Med. 2011, 1, a007278.

T. Zhou, I. Georgiev, X. Wu, Z.Y. Yang, K. Dai, A. Finzi, Y.D. Kwon, J.F. Scheidet. al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 2010, 329, 811-7.

R. Pejchal, K.J. Doores, L.M. Walker, R. Khayat, P.S. Huang, S.K. Wang, R.L. Stanfield, J.P. Julienet. al. A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science 2011, 334, 1097-103.

V. Beena, K. Choudhary, R. Rajeev, R. Sivakumar, R. Heera, S. Padmakumar. Human immunodeficiency virus vaccine an update. J. Oral Maxillofac. Path. 2013, 17, 76-81.

M.H. Malim, P.D. Bieniasz. HIV Restriction Factors and Mechanisms of Evasion. Cold Spring Harbor Perspect. Med. 2012, 2, a006940.

N. Van Damme, D. Goff, C. Katsura, R.L. Jorgenson, R. Mitchell, M.C. Johnson, E.B. Stephens, J. Guatelli. The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe 2008, 3, 245-52.

H. Yang, X. Ji, G. Zhao, J. Ning, Q. Zhao, C. Aiken, A.M. Gronenborn, P. Zhang, Y. Xiong. Structural insight into HIV-1 capsid recognition by rhesus TRIM5alpha. Proc. Nat. Acad. Sci. 2012, 109, 18372-7.

K. Gillick, D. Pollpeter, P. Phalora, E.Y. Kim, S.M. Wolinsky, M.H. Malim. Suppression of HIV-1 infection by APOBEC3 proteins in primary human CD4(+) T cells is associated with inhibition of processive reverse transcription as well as excessive cytidine deamination. J. Virol. 2013, 87, 1508-17.

Z. Chen, L. Zhang, S. Ying. SAMHD1: a novel antiviral factor in intrinsic immunity. Future Microbiol. 2012, 7, 1117-26.

J. Bitzegeio, M. Sampias, P.D. Bieniasz, T. Hatziioannou. Adaptation to the interferon-induced antiviral state by human and simian immunodeficiency viruses. J. Virol. 2013, 87, 3549-60.

S.K. Pillai, M. Abdel-Mohsen, J. Guatelli, M. Skasko, A. Monto, K. Fujimoto, S. Yukl, W.C. Greeneet. al. Role of retroviral restriction factors in the interferon-alpha-mediated suppression of HIV-1 in vivo. Proc. Nat. Acad. Sci. 2012, 109, 3035-40.

L.M. Sedger. microRNA control of interferons and interferon induced anti-viral activity. Mol. Immunol. 2013, 56, 781-93.

C. Goujon, O. Moncorge, H. Bauby, T. Doyle, C.C. Ward, T. Schaller, S. Hue, W.S. Barclayet. al. Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection. Nature 2013.

C. Uwah, S. Wright. Socio-cultural identities, perceptions of sexuality/sexual behavior and cultural contexts as determinants of HIV and AIDS prevalence in Southern Africa. World J. AIDS 2012, 2, 17-23.

B. Craven, G. Stewart. Economic implications of socio-cultural correlates of HIV/AIDS: an analysis of global data. Appl. Econom. 2013, 45, 1789-800.

M. Vranda, S. Mothi. Psychosocial issues of children infected with HIV/AIDS. Ind. J. Psychol. Med. 2013, 35, 19.

V.K. Shanwal, G. Kaur. Emotional Reactions Associated with HIV/AIDS. 2010 PsyInsight p25.

J.S. Grant, D. Vance, W. White, N. Keltner, J. Raper. Why people living with HIV/AIDS exclude individuals from their chosen families. Nursing: Res. 2013, 3, 33-42.

A.T. Olagunju, J.D. Adeyemi, R.E. Ogbolu, E.A. Campbell. A study on epidemiological profile of anxiety disorders among people living with HIV/AIDS in a Sub-Saharan Africa HIV Clinic. AIDS Behav. 2012, 16, 2192-97.

M. Khan, A. Sehgal. Clinico-epidemiological and socio-behavioral study of people living with HIV/AIDS. Ind. J. Psychol. Med. 2010, 32, 22.

ISSN 2347–9825

Authors/visitors are advised to use Firefox browser for better experience of journal site.

Open Access: Researcher from developing/low economy countries can access the jorunal contents through WHO-HINARI .