When to start antiretroviral therapy: The need for an evidence base during early HIV infection

BMC Medicine

Volumn 11, Issue 1, 2013, Pages

  Lundgren, Jens D ^a,b   Babiker, Abdel G ^c   Gordin, Fred M ^d   Borges, Álvaro H ^a,b   Neaton, James D ^e  

^a Rigshospitalet   (Denmark)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c MRC CLINICAL TRIALS UNIT   (United Kingdom)

^d GEORGE WASHINGTON UNIVERSITY   (United States)

^e UNIVERSITY OF MINNESOTA   (United States)

Author keywords

Antiretroviral therapy; Benefit; CD4 count; Drug toxicity; HIV; Risk ratio; Treatment as prevention

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT;

ARTICLE; CD4 LYMPHOCYTE COUNT; DISEASE ASSOCIATION; EVIDENCE BASED PRACTICE; HETEROSEXUALITY; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFECTION RISK; META ANALYSIS; PHYSICIAN; PRACTICE GUIDELINE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK BENEFIT ANALYSIS; VIRUS TRANSMISSION; WORLD HEALTH ORGANIZATION; ANIMAL; HIV INFECTIONS; PROCEDURES; METHODOLOGY; NOTE;

ANIMALS; ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; HIV INFECTIONS; HUMANS;

EID: 84878895392     PISSN: None     EISSN: 17417015     Source Type: Journal    
DOI: 10.1186/1741-7015-11-148     Document Type: Article

References (91)

1. Hahn BH, Shaw GM, De Cock KM, Sharp PM. AIDS as a zoonosis: scientific and public health implications. Science 2000, 287:607-614. 10.1126/science.287.5453.607, 10649986.
2. UNAIDS 2012 UNAIDS Report on the Global AIDS Epidemic 2012 http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2012/gr2012/20121120_UNAIDS_Global_Report_2012_with_annexes_en.pdf, UNAIDS 2012.
3. Graw F, Leitner T, Ribeiro RM. Agent-based and phylogenetic analyses reveal how HIV-1 moves between risk groups: injecting drug users sustain the heterosexual epidemic in Latvia. Epidemics 2012, 4:104-116. 10.1016/j.epidem.2012.04.002, 3405853, 22664069.
4. Munier CM, Andersen CR, Kelleher AD. HIV vaccines: progress to date. Drugs 2011, 71:387-414.
5. Gray RH, Kigozi G, Serwadda D, Makumbi F, Watya S, Nalugoda F, Kiwanuka N, Moulton LH, Chaudhary MA, Chen MZ, Sewankambo NK, Wabwire-Mangen F, Bacon MC, Williams CF, Opendi P, Reynolds SJ, Laeyendecker O, Quinn TC, Wawer MJ. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet 2007, 369:657-666. 10.1016/S0140-6736(07)60313-4, 17321311.
6. Wawer MJ, Makumbi F, Kigozi G, Serwadda D, Watya S, Nalugoda F, Buwembo D, Ssempijja V, Kiwanuka N, Moulton LH, Sewankambo NK, Reynolds SJ, Quinn TC, Opendi P, Iga B, Ridzon R, Laeyendecker O, Gray RH. Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial. Lancet 2009, 374:229-237. 10.1016/S0140-6736(09)60998-3, 2905212, 19616720.
7. Drucker E, Lurie P, Wodak A, Alcabes P. Measuring harm reduction: the effects of needle and syringe exchange programs and methadone maintenance on the ecology of HIV. AIDS 1998, 12:217-230. 10.1097/00002030-199817000-00002, 9468372.
8. Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O'Sullivan MJ, VanDyke R, Bey M, Shearer W, Jacobson RL. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS clinical trials group protocol 076 study group. N Engl J Med 1994, 331:1173-1180. 10.1056/NEJM199411033311801, 7935654.
9. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Mehendale S, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Wang L, Makhema J, Mills LA, de Bruyn G, Sanne I, Eron J, Gallant J, Havlir D, Swindells S, Ribaudo H, Elharrar V, Burns D, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011, 365:493-505. 10.1056/NEJMoa1105243, 3200068, 21767103.
10. Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, d'Arminio Monforte A, Yust I, Bruun JN, Phillips AN, Lundgren JD. Changing patterns of mortality across Europe in patients infected with HIV-1. EuroSIDA study group. Lancet 1998, 352:1725-1730. 10.1016/S0140-6736(98)03201-2, 9848347.
11. Bhaskaran K, Hamouda O, Sannes M, Boufassa F, Johnson AM, Lambert PC, Porter K, CASCADE Collaboration Changes in the risk of death after HIV seroconversion compared with mortality in the general population. JAMA 2008, 300:51-59. 10.1001/jama.300.1.51, 18594040, CASCADE Collaboration.
12. Hammer SM, Squires KE, Hughes MD, Grimes JM, Demeter LM, Currier JS, Eron JJ, Feinberg JE, Balfour HH, Deyton LR, Chodakewitz JA, Fischl MA. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS clinical trials group 320 study team. N Engl J Med 1997, 337:725-733. 10.1056/NEJM199709113371101, 9287227.
13. El-Sadr WM, Lundgren J, Neaton JD, Gordin F, Abrams D, Arduino RC, Babiker A, Burman W, Clumeck N, Cohen CJ, Cohn D, Cooper D, Darbyshire J, Emery S, Fätkenheuer G, Gazzard B, Grund B, Hoy J, Klingman K, Losso M, Markowitz N, Neuhaus J, Phillips A, Rappoport C. CD4+ count-guided interruption of antiretroviral therapy. N Engl J Med 2006, 355:2283-2296.
14. World Health Organization Scaling up Antiretroviral Therapy in Resource-Limited Settings: Treatment Guidelines for a Public Health Approach 2003 revision 2004, Geneva, Switzerland: WHO, World Health Organization.
15. World Health Organization Antiretroviral Therapy for HIV Infection in Adults and Adolescents Recommendations for a Public Health Approach 2010 revision 2010, Geneva, Switzerland, World Health Organization.
16. Thompson MA, Aberg JA, Hoy JF, Telenti A, Benson C, Cahn P, Eron JJ, Gunthard HF, Hammer SH, Reiss P, Richman DD, Rizzardini G, Thomas DL, Jacobsen DM, Volberding PA. Antiretroviral Treatment of Adult HIV Infection: 2012 Recommendations of the International Antiviral Society-USA Panel. JAMA 2012, 308:387-402. 10.1001/jama.2012.7961, 22820792.
17. Williams I, Churchill D, Anderson J, Boffito M, Bower M, Cairns G, Cwynarski K, Edwards S, Fidler S, Fisher M, Freedman A, Geretti AM, Gilleece Y, Horne R, Johnson M, Khoo S, Leen C, Marshall N, Nelson M, Orkin C, Paton N, Phillips A, Post F, Pozniak A, Sabin C, Trevelion R, Ustianowski A, Walsh J, Waters L, Wilkins E, et al. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012. HIV Med 2012, 13:1-85.
18. European AIDS Clinical Society European Guidelines for treatment of HIV infected adults in Europe http://www.europeanaidsclinicalsociety.org/images/stories/EACS-Pdf/EacsGuidelines-v6.1-2edition.pdf, European AIDS Clinical Society.
19. Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf, Department of Health and Human Services.
20. Franco R, Saag MS. When to start antiretroviral therapy: as soon as possible. BMC Med 2013, 11:147.
21. Hamers FF, Phillips AN. Diagnosed and undiagnosed HIV-infected populations in Europe. HIV Med 2008, 9:6-12.
22. Lundgren JD, COHERE in EuroCoord Characteristics of individuals with HIV presenting late for care across Europe. Program and abstracts of the XIX International AIDS Conference: 22-27 July 2012 Washington, DC, Oral Presentation, COHERE in EuroCoord.
23. Sabin CA, Schwenk A, Johnson MA, Gazzard B, Fisher M, Walsh J, Orkin C, Hill T, Gilson R, Porter K, Easterbrook P, Delpech V, Bansi L, Leen C, Gompels M, Anderson J, Phillips AN. Late diagnosis in the HAART era: proposed common definitions and associations with mortality. AIDS 2010, 24:723-727.
24. Nakagawa F, Lodwick RK, Smith CJ, Smith R, Cambiano V, Lundgren JD, Delpech V, Phillips AN. Projected life expectancy of people with HIV according to timing of diagnosis. AIDS 2012, 26:335-343. 10.1097/QAD.0b013e32834dcec9, 22089374.
25. Schackman BR, Freedberg KA, Weinstein MC, Sax PE, Losina E, Zhang H, Goldie SJ. Cost-effectiveness implications of the timing of antiretroviral therapy in HIV-infected adults. Arch Intern Med 2002, 162:2478-2486. 10.1001/archinte.162.21.2478, 12437408.
26. Fisher M. Late diagnosis of HIV infection: major consequences and missed opportunities. Curr Opin Infect Dis 2008, 21:1-3. 10.1097/QCO.0b013e3282f2d8fb, 18192778.
27. Sullivan AK, Raben D, Reekie J, Rayment M, Mocroft A, Esser S, Leon A, Begovac J, Brinkman K, Zangerle R, Grzeszczuk A, Vassilenko A, Hadziosmanovic V, Krasnov M, Sönnerborg A, Clumeck N, Gatell J, Gazzard B, Monforte AD, Rockstroh J, Lundgren JD. Feasibility and effectiveness of indicator condition-guided testing for HIV: results from HIDES I (HIV indicator diseases across Europe study). PLoS One 2013, 8:e52845. 10.1371/journal.pone.0052845, 3546115, 23341910.
28. Weiss SH, Goedert JJ, Sarngadharan MG, Bodner AJ, Gallo RC, Blattner WA. Screening test for HTLV-III (AIDS agent) antibodies. Specificity, sensitivity, and applications. JAMA 1985, 253:221-225. 10.1001/jama.1985.03350260073029, 2981369.
29. Emery S, Neuhaus JA, Phillips AN, Babiker A, Cohen CJ, Gatell JM, Girard PM, Grund B, Law M, Losso MH, Palfreeman A, Wood R. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis 2008, 197:1133-1144.
30. Severe P, Juste MA, Ambroise A, Eliacin L, Marchand C, Apollon S, Edwards A, Bang H, Nicotera J, Godfrey C, Gulick RM, Johnson WD, Pape JW, Fitzgerald DW. Early versus standard antiretroviral therapy for HIV-infected adults in Haiti. N Engl J Med 2010, 363:257-265. 10.1056/NEJMoa0910370, 3676927, 20647201.
31. Kitahata MM, Gange SJ, Abraham AG, Merriman B, Saag MS, Justice AC, Hogg RS, Deeks SG, Eron JJ, Brooks JT, Rourke SB, Gill MJ, Bosch RJ, Martin JN, Klein MB, Jacobson LP, Rodriguez B, Sterling TR, Kirk GD, Napravnik S, Rachlis AR, Calzavara LM, Horberg MA, Silverberg MJ, Gebo KA, Goedert JJ, Benson CA, Collier AC, Van Rompaey SE. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 2009, 360:1815-1826. 10.1056/NEJMoa0807252, 2854555, 19339714.
32. Sterne JA, May M, Costagliola D, de Wolf F, Phillips AN, Harris R, Funk MJ, Geskus RB, Gill J, Dabis F, Miró JM, Justice AC, Ledergerber B, Fätkenheuer G, Hogg RS, Monforte AD, Saag M, Smith C, Staszewski S, Egger M, Cole SR. Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies. Lancet 2009, 373:1352-1363. 2670965, 19361855.
33. CASCADE Collaboration Timing of HAART initiation and clinical outcomes in human immunodeficiency virus type 1 seroconverters. Arch Intern Med 2011, 171:1560-1569. 10.1001/archinternmed.2011.401, 21949165, CASCADE Collaboration.
34. Cain LE, Logan R, Robins JM, Sterne JA, Sabin C, Bansi L, Justice A, Goulet J, van Sighem A, de Wolf F, Bucher HC, von Wyl V, Esteve A, Casabona J, del Amo J, Moreno S, Seng R, Meyer L, Perez-Hoyos S, Muga R, Lodi S, Lanoy E, Costagliola D, Hernan MA. When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: an observational study. Ann Intern Med 2011, 154:509-515. 3610527, 21502648.
35. Siegfried N, Uthman OA, Rutherford GW. Optimal time for initiation of antiretroviral therapy in asymptomatic, HIV-infected, treatment-naive adults. Cochrane Database Syst Rev 2010, 3:CD008272.
36. Grinsztejn B, Hosseinipour M, Swindells S. Effect of early versus delayed initiation of antiretroviral therapy (ART) on clinical outcomes in the HPTN 052 randomized clinical trial. Program and abstracts of the XIX International AIDS Conference: 22-27 July 2012 Washington DC, Abstract THLBB05.
37. Abrams D, Lévy Y, Losso MH, Babiker A, Collins G, Cooper DA, Darbyshire J, Emery S, Fox L, Gordin F, Lane HC, Lundgren JD, Mitsuyasu R, Neaton JD, Phillips A, Routy JP, Tambussi G, Wentworth D. Interleukin-2 therapy in patients with HIV infection. N Engl J Med 2009, 361:1548-1559.
38. El-Sadr WM, Grund B, Neuhaus J, Babiker A, Cohen CJ, Darbyshire J, Emery S, Lundgren JD, Phillips A, Neaton JD. Risk for opportunistic disease and death after reinitiating continuous antiretroviral therapy in patients with HIV previously receiving episodic therapy: a randomized trial. Ann Intern Med 2008, 149:289-299.
39. Mugavero MJ, Napravnik S, Cole SR, Eron JJ, Lau B, Crane HM, Kitahata MM, Willig JH, Moore RD, Deeks SG, Saag MS, Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) Cohort Study Viremia copy-years predicts mortality among treatment-naive HIV-infected patients initiating antiretroviral therapy. Clin Infect Dis 2011, 53:927-935. 10.1093/cid/cir526, 3189165, 21890751, Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) Cohort Study.
40. Reekie J, Gatell JM, Yust I, Bakowska E, Rakhmanova A, Losso M, Krasnov M, Francioli P, Kowalska JD, Mocroft A, EuroSIDA in EuroCoord Fatal and nonfatal AIDS and non-AIDS events in HIV-1-positive individuals with high CD4 cell counts according to viral load strata. AIDS 2011, 25:2259-2268. 10.1097/QAD.0b013e32834cdb4b, 21918422, EuroSIDA in EuroCoord.
41. Lodwick RK, Sabin CA, Porter K, Ledergerber B, van Sighem A, Cozzi-Lepri A, Khaykin P, Mocroft A, Jacobson L, De Wit S, Obel N, Castagna A, Wasmuth JC, Gill J, Klein MB, Gange S, Riera M, Mussini C, Gutiérrez F, Touloumi G, Carrieri P, Guest JL, Brockmeyer NH, Phillips AN, Study Group on Death Rates at High CD4 Count in Antiretroviral Naive Patients Death rates in HIV-positive antiretroviral-naive patients with CD4 count greater than 350 cells per microL in Europe and North America: a pooled cohort observational study. Lancet 2010, 376:340-345. 3085917, 20638118, Study Group on Death Rates at High CD4 Count in Antiretroviral Naive Patients.
42. Rodger AJ, Lodwick R, Schechter M, Deeks S, Amin J, Gilson R, Paredes R, Bakowska E, Engsig F, Phillips AN, INSIGHT SMART, ESPRIT Study Groups Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population. AIDS 2013, 27:973-979. 10.1097/QAD.0b013e32835cae9c, 23698063, INSIGHT SMART, ESPRIT Study Groups.
43. Kaufmann GR, Furrer H, Ledergerber B, Perrin L, Opravil M, Vernazza P, Cavassini M, Bernasconi E, Rickenbach M, Hirschel B, Battegay M, Swiss HIV Cohort Study Characteristics, determinants, and clinical relevance of CD4 T cell recovery to <500 cells/microL in HIV type 1-infected individuals receiving potent antiretroviral therapy. Clin Infect Dis 2005, 41:361-372. 10.1086/431484, 16007534, Swiss HIV Cohort Study.
44. Mocroft A, Phillips AN, Gatell J, Ledergerber B, Fisher M, Clumeck N, Losso M, Lazzarin A, Fatkenheuer G, Lundgren JD, EuroSIDA study group Normalisation of CD4 counts in patients with HIV-1 infection and maximum virological suppression who are taking combination antiretroviral therapy: an observational cohort study. Lancet 2007, 370:407-413. 10.1016/S0140-6736(07)60948-9, 17659333, EuroSIDA study group.
45. Sabin CA, Cooper DA, Collins S, Schechter M. Rating evidence in treatment guidelines: a case example of when to initiate combination antiretroviral therapy (cART) in HIV-positive asymptomatic persons. AIDS In press.
46. Touloumi G, Pantazis N, Pillay D, Paraskevis D, Chaix ML, Bucher HC, Kücherer C, Zangerle R, Kran AM, Porter K, CASCADEcollaboration in EuroCoord Impact of HIV-1 subtype on CD4 count at HIV seroconversion, rate of decline, and viral load set point in European seroconverter cohorts. Clin Infect Dis 2013, 56:888-897. 10.1093/cid/cis1000, 23223594, CASCADEcollaboration in EuroCoord.
47. Kenedi CA, Goforth HW. A systematic review of the psychiatric side-effects of efavirenz. AIDS Behav 2011, 15:1803-1818. 10.1007/s10461-011-9939-5, 21484283.
48. Robertson K, Liner J, Meeker RB. Antiretroviral neurotoxicity. J Neurovirol 2012, 18:388-399. 10.1007/s13365-012-0120-3, 22811264.
49. Scourfield A, Zheng J, Chinthapalli S, Waters L, Martin T, Mandalia S, Nelson M. Discontinuation of Atripla as first-line therapy in HIV-1 infected individuals. AIDS 2012, 26:1399-1401. 10.1097/QAD.0b013e328353b047, 22441251.
50. Rockwood N, Mandalia S, Bower M, Gazzard B, Nelson M. Ritonavir-boosted atazanavir exposure is associated with an increased rate of renal stones compared with efavirenz, ritonavir-boosted lopinavir and ritonavir-boosted darunavir. AIDS 2011, 25:1671-1673. 10.1097/QAD.0b013e32834a1cd6, 21716074.
51. Young J, Schäfer J, Fux CA, Furrer H, Bernasconi E, Vernazza P, Calmy A, Cavassini M, Weber R, Battegay M, Bucher HC, Swiss HIV Cohort Study Renal function in patients with HIV starting therapy with tenofovir and either efavirenz, lopinavir or atazanavir. AIDS 2012, 26:567-575. 10.1097/QAD.0b013e32834f337c, 22398568, Swiss HIV Cohort Study.
52. Ryom L, Mocroft A, Kirk O, Worm SW, Kamara DA, Reiss P, Ross M, Fux CA, Morlat P, Moranne O, Smith C, Lundgren JD, D:A:D study group Exposure to antiretrovirals (ARVs) and risk of renal impairment among HIV-positive persons with normal baseline renal function: the D:A:D study. J Infect Dis 2013, 207:1359-1369. 10.1093/infdis/jit043, 23382571, D:A:D study group.
53. Bedimo R, Maalouf NM, Zhang S, Drechsler H, Tebas P. Osteoporotic fracture risk associated with cumulative exposure to tenofovir and other antiretroviral agents. AIDS 2012, 26:825-831. 10.1097/QAD.0b013e32835192ae, 22301411.
54. Baum PD, Sullam PM, Stoddart CA, McCune JM. Abacavir increases platelet reactivity via competitive inhibition of soluble guanylyl cyclase. AIDS 2011, 25:2243-2248. 10.1097/QAD.0b013e32834d3cc3, 3272328, 21941165.
55. Worm SW, Sabin C, Weber R, Reiss P, El-Sadr W, Dabis F, De Wit S, Law M, Monforte AD, Friis-Møller N, Kirk O, Fontas E, Weller I, Phillips A, Lundgren J. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study. J Infect Dis 2010, 201:318-330. 10.1086/649897, 20039804.
56. Saint-Marc T, Partisani M, Poizot-Martin I, Bruno F, Rouviere O, Lang JM, Gastaut JA, Touraine JL. A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. AIDS 1999, 13:1659-1667. 10.1097/00002030-199909100-00009, 10509567.
57. Carr A, Miller J, Law M, Cooper DA. A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome. AIDS 2000, 14:25-32.
58. Chao C, Leyden WA, Xu L, Horberg MA, Klein D, Towner WJ, Quesenberry CP, Abrams DI, Silverberg MJ. Exposure to antiretroviral therapy and risk of cancer in HIV-infected persons. AIDS 2012, 26:2223-2231. 10.1097/QAD.0b013e32835935b3, 22951631.
59. Bruyand M, Ryom L, Shepherd L, Reiss P, De Wit S, D'Arminio Monforte A, Rickenbach M, Philips A, Lundgren JD, Sabin C, D:A:D study group Cancer Risk and Use of PI or NNRTI-based Combination Antiretroviral Therapy (cART): the D:A:D study. Program and abstracts of the XX Conference on Retroviruses and Opportunistic Infections: 2-6 March 2013 Atlanta, USA, Abstract Q-1002, D:A:D study group.
60. Lichtenstein KA, Armon C, Baron A, Moorman AC, Wood KC, Holmberg SD, HIV Outpatient Study Investigators Modification of the incidence of drug-associated symmetrical peripheral neuropathy by host and disease factors in the HIV outpatient study cohort. Clin Infect Dis 2005, 40:148-157. 10.1086/426076, 15614705, HIV Outpatient Study Investigators.
61. Lichtenstein KA, Armon C, Buchacz K, Chmiel JS, Moorman AC, Wood KC, Holmberg SD, Brooks JT, HIV Outpatient Study (HOPS) Investigators Initiation of antiretroviral therapy at CD4 cell counts >/=350 cells/mm3 does not increase incidence or risk of peripheral neuropathy, anemia, or renal insufficiency. J Acquir Immune Defic Syndr 2008, 47:27-35. 10.1097/QAI.0b013e31815acacc, 17971714, HIV Outpatient Study (HOPS) Investigators.
62. Baker JV, Peng G, Rapkin J, Abrams DI, Silverberg MJ, MacArthur RD, Cavert WP, Henry WK, Neaton JD, Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) CD4+ count and risk of non-AIDS diseases following initial treatment for HIV infection. AIDS 2008, 13:841-848. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA).
63. Moore RD, Gebo KA, Lucas GM, Keruly JC. Rate of comorbidities not related to HIV infection or AIDS among HIV-infected patients, by CD4 cell count and HAART use status. Clin Infect Dis 2008, 47:1102-1104. 10.1086/592115, 2597666, 18781885.
64. Achhra AC, Amin J, Law MG, Emery S, Gerstoft J, Gordin FM, Vjecha MJ, Neaton JD, Cooper DA, INSIGHT ESPRIT & SILCAAT study groups Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients. AIDS 2010, 24:1877-1886. 10.1097/QAD.0b013e32833b1b26, 2902669, 20588170, INSIGHT ESPRIT & SILCAAT study groups.
65. Smith C, Sabin CA, Lundgren JD, Thiebaut R, Weber R, Law M, Monforte A, Kirk O, Friis-Moller N, Phillips A, Reiss P, El Sadr W, Pradier C, Worm SW. Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D study. AIDS 2010, 24:1537-1548.
66. Rose G. Strategy of prevention: lessons from cardiovascular disease. Br Med J (Clin Res Ed) 1981, 282:1847-1851.
67. Schechter M. Therapy for early HIV infection: how far back should the pendulum swing?. J Infect Dis 2004, 190:1043-1045. 10.1086/422852, 15319851.
68. De Cock K-M, El-Sadr W. When to start ART in Africa - an urgent research priority. N Engl J Med 2013, 368:886-889. 10.1056/NEJMp1300458, 23425131.
69. Kowalska JD, Kirk O, Mocroft A, Høj L, Friis-Møller N, Reiss P, Weller I, Lundgren JD. Implementing the number needed to harm in clinical practice: risk of myocardial infarction in HIV-1-infected patients treated with abacavir. HIV Med 2010, 11:200-208. 10.1111/j.1468-1293.2009.00763.x, 19863618.
70. Babiker AG, Emery S, Fätkenheuer G, Gordin FM, Grund B, Lundgren JD, Neaton JD, Pett SL, Phillips A, Touloumi G, Vjecha MJ. Considerations in the rationale, design and methods of the strategic timing of AntiRetroviral treatment (START) study. Clin Trials 2013, 10:S5-S36. Epub ahead of print, 10.1177/1740774512440342, 3664112, 22547421.
71. Getahun H, Gunneberg C, Granich R, Nunn P. HIV infection-associated tuberculosis: the epidemiology and the response. Clin Infect Dis 2010, 50:201-207.
72. Suthar A-B, Lawn S-D, del Amo J, Getahun H, Dye C, Sculier D, Sterling TR, Chaisson RE, Williams BG, Harries AD, Granich RM. Antiretroviral therapy for prevention of tuberculosis in adults with HIV: a systematic review and meta-analysis. PLoS Med 2012, 9:e1001270. 10.1371/journal.pmed.1001270, 3404110, 22911011.
73. Bearman JE, Loewenson RB, Gullen WH. Muench's Postulates, Laws and Corollaries, or Biometrician's Views on Clinical Studies (Biometric Note 4) 1974, Bethesda (MD): Office of Biometry and Epidemiology, National Eye Institute, National Institutes of Health.
74. Cohen MS, Gay CL. Treatment to prevent transmission of HIV-1. Clin Infect Dis 2010, 50:85-95. 10.1086/648724, 19951231.
75. Shelton J. ARVs as HIV prevention: a tough road to wide impact. Science 2011, 334:1645-1646. 10.1126/science.1212353, 22194560.
76. World Health Organization Antiretroviral treatment as prevention (TASP) of HIV and TB Programmatic update http://whqlibdoc.who.int/hq/2012/WHO_HIV_2012.12_eng.pdf, World Health Organization.
77. Tanser F, Bärnighausen T, Grapsa E, Zaidi J, Newell ML. High coverage of ART associated with decline in risk of HIV acquisition in rural KwaZulu-Natal, South Africa. Science 2013, 339:966-971. 10.1126/science.1228160, 23430656.
78. Dukers NH, Goudsmit J, de Wit JB, Prins M, Weverling GJ, Coutinho RA. Sexual risk behaviour relates to the virological and immunological improvements during highly active antiretroviral therapy in HIV-1 infection. AIDS 2001, 15:369-378. 10.1097/00002030-200102160-00010, 11273217.
79. Stolte IG, Dukers NH, Geskus RB, Coutinho RA, de Wit JB. Homosexual men change to risky sex when perceiving less threat of HIV/AIDS since availability of highly active antiretroviral therapy: a longitudinal study. AIDS 2004, 18:303-309. 10.1097/00002030-200401230-00021, 15075549.
80. Phillips AN, Cambiano V, Nakagawa F, Brown AE, Lampe F, Rodger A, Miners A, Elford J, Hart G, Johnson AM, Lundgren J, Delpech VC. Increased HIV incidence in men who have sex with men despite high levels of ART-induced viral suppression: analysis of an extensively documented epidemic. PLoS One 2013, In press.
81. Ostrow DE, Fox KJ, Chmiel JS, Silvestre A, Visscher BR, Vanable PA, Jacobson LP, Strathdee SA. Attitudes towards highly active antiretroviral therapy are associated with sexual risk taking among HIV-infected and uninfected homosexual men. AIDS 2002, 16:775-780. 10.1097/00002030-200203290-00013, 11964534.
82. Powers KA, Ghani AC, Miller WC, Hoffman IF, Pettifor AE, Kamanga G, Martinson FE, Cohen MS. The role of acute and early HIV infection in the spread of HIV and implications for transmission prevention strategies in Lilongwe, Malawi: a modelling study. Lancet 2011, 378:256-268. 10.1016/S0140-6736(11)60842-8, 3274419, 21684591.
83. Quinn TC, Wawer MJ, Sewankambo N, Serwadda D, Li C, Wabwire-Mangen F, Meehan MO, Lutalo T, Gray RH. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med 2000, 342:921-929. 10.1056/NEJM200003303421303, 10738050.
84. Wawer MJ, Gray RH, Sewankambo NK, Serwadda D, Li X, Laeyendecker O, Kiwanuka N, Kigozi G, Kiddugavu M, Lutalo T, Nalugoda F, Wabwire-Mangen F, Meehan MP, Quinn TC. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis 2005, 191:1403-1409. 10.1086/429411, 15809897.
85. Granich R, Gupta S, Suthar AB, Smyth C, Hoos D, Vitoria M, Simao M, Hankins C, Schwartlander B, Ridzon R, Bazin B, Williams B, Lo YR, McClure C, Montaner J, Hirnschall G, ART in Prevention of HIV and TB Research Writing Group Antiretroviral therapy in prevention of HIV and TB: update on current research efforts. Curr HIV Res 2011, 9:446-469. 10.2174/157016211798038597, 3531820, 21999779, ART in Prevention of HIV and TB Research Writing Group.
86. van Griensven J, Zachariah R, Rasschaert F, Mugabo J, Atté EF, Reid T. Stavudine- and nevirapine-related drug toxicity while on generic fixed-dose antiretroviral treatment: incidence, timing and risk factors in a three-year cohort in Kigali, Rwanda. Trans R Soc Trop Med Hyg 2010, 104:148-153. 10.1016/j.trstmh.2009.07.009, 19732926.
87. Phan V, Thai S, Choun K, Lynen L, van Griensven J. Incidence of treatment-limiting toxicity with stavudine-based antiretroviral therapy in Cambodia: a retrospective cohort study. PLoS One 2012, 7:e30647. 10.1371/journal.pone.0030647, 3267733, 22303447.
88. Stadeli KM, Richman DD. Rates of emergence of HIV drug resistance in resource-limited settings: a systematic review. Antivir Ther 2012, 18:115-123. 10.3851/IMP2437, 23052978.
89. Prasad V, Cifu A, Ioannidis JP. Reversals of established medical practices: evidence to abandon ship. JAMA 2012, 307:37-38. 10.1001/jama.2011.1960, 22215160.
90. Fidler S, Porter K, Ewings F, Frater J, Ramjee G, Cooper D, Rees H, Fisher M, Schechter M, Kaleebu P, Tambussi G, Kinloch S, Miro JM, Kelleher A, McClure M, Kaye S, Gabriel M, Phillips R, Weber J, Babiker A. Short-course antiretroviral therapy in primary HIV infection. N Engl J Med 2013, 368:207-217.
91. Le T, Wright EJ, Smith DM, He W, Catano G, Okulicz JF, Young JA, Clark RA, Richman DD, Little SJ, Ahuja SK. Enhanced CD4+ T-cell recovery with earlier HIV-1 antiretroviral therapy. N Engl J Med 2013, 368:218-230. 10.1056/NEJMoa1110187, 23323898.