Papers of particular interest, published recently, have been highlighted as:
• Of importance
•• Of major importance
1. Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med. 2000;342:921–929. [PubMed] 2. Garcia PM, Kalish LA, Pitt J, et al. Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Infants Transmission Study Group. N Engl J Med. 1999;341:394–402. [PubMed] 3. Richardson BA, John-Stewart GC, Hughes JP, et al. Breast-milk infectivity in human immunodeficiency virus type 1-infected mothers. J Infect Dis. 2003;187:736–740. [PMC free article] [PubMed] 4. Fideli US, Allen SA, Musonda R, et al. Virologic and immunologic determinants of heterosexual transmission of human immunodeficiency virus type 1 in Africa. AIDS Res Hum Retroviruses. 2001;17:901–910. [PMC free article] [PubMed] 5. Tovanabutra S, Robison V, Wongtrakul J, et al. Male viral load and heterosexual transmission of HIV-1 subtype E in northern Thailand. J Acquir Immune Defic Syndr. 2002;29:275–283. [PubMed] 6. Coombs RW, Reichelderfer PS, Landay AL. Recent observations on HIV type-1 infection in the genital tract of men and women. AIDS. 2003;17:455–480. [PubMed] 7. Lampinen TM, Critchlow CW, Kuypers JM, et al. Association of antiretroviral therapy with detection of HIV-1 RNA and DNA in the anorectal mucosa of homosexual men. AIDS. 2000;14:F69–F75. [PubMed] 8. Cohen MS, Hoffman IF, Royce RA, et al. Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. AIDSCAP Malawi Research Group. Lancet. 1997;349:1868–1873. [PubMed] 9. Ghys PD, Fransen K, Diallo MO, et al. The associations between cervicovaginal HIV shedding, sexually transmitted diseases and immunosuppression in female sex workers in Abidjan, Cote d’Ivoire. AIDS. 1997;11:F85–F93. [PubMed] 10. Pilcher CD, Joaki G, Hoffman IF, et al. Amplified transmission of HIV-1: comparison of HIV-1 concentrations in semen and blood during acute and chronic infection. AIDS. 2007;21:1723–1730. [PMC free article] [PubMed] 11.
Wawer MJ, Gray RH, Sewankambo NK, et al. Rates of HIV-1 transmission per coital, act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis. 2005;191:1403–1409. [PubMed]
This retrospective study found that the risk of HIV transmission among serodiscordant couples was highest during early HIV infection and was associated with high viral load. 12.
Brenner BG, Roger M, Routy JP, et al. High rates of forward transmission events after acute/early HIV-1 infection. J Infect Dis. 2007;195:951–959. [PubMed]
This study using phylogenetic analysis concluded that approximately half of incident HIV in a North American cohort was related to early HIV infection. 13.
Were WA, Mermin JH, Wamai N, et al. Undiagnosed HIV infection and couple HIV discordance among household members of HIV-infected people receiving antiretroviral therapy in Uganda. J Acquir Immune Defic Syndr. 2006;43:91–95. [PubMed]
A massive household HIV testing campaign in Uganda revealed that 37.1% of adults ages 25 to 44 years were HIV infected, and that 43% of partners of HIV-infected individuals were HIV negative 14. Musicco M, Lazzarin A, Nicolosi A, et al. Antiretroviral treatment of men infected with human immunodeficiency virus type 1 reduces the incidence of heterosexual transmission. Italian Study Group on HIV Heterosexual Transmission. Arch Intern Med. 1994;154:1971–1976. [PubMed] 15. Castilla J, Del Romero J, Hernando V, et al. Effectiveness of highly active antiretroviral therapy in reducing heterosexual transmission of HIV. J Acquir Immune Defic Syndr. 2005;40:96–101. [PubMed]
Kayitenkore K, Bekan B, Rufagari J, et al. The impact of ART on HIV transmission among HIV serodiscordant couples; Presented at the XVI International AIDS Conference; Toronto, Canada: [August 13–16, 2006].
This case-controlled study reported that ART initiated in HIV-infected individuals in a serodiscordant relationship with CD4 count less than 200 cells/mL and/or advanced HIV disease decreased HIV transmission to partners after adjustment for condom use.
Bunnell R, Ekwaru JP, Solberg P, et al. Changes in sexual behavior and risk of HIV transmission after antiretroviral therapy and prevention interventions in rural Uganda. AIDS. 2006;20:85–92. [PubMed]
A prospective study in rural Uganda found that the risk of HIV transmission among serodiscordant couples decreased from 45.7 to 0.9 per 100 person-years following ART initiation in the infected partner 18. Porco TC, Martin JN, Page-Shafer KA, et al. Decline in HIV infectivity following the introduction of highly active antiretroviral therapy. AIDS. 2004;18:81–88. [PMC free article] [PubMed] 19. Fang CT, Hsu HM, Twu SJ, et al. Decreased HIV transmission after a policy of providing free access to highly active antiretroviral therapy in Taiwan. J Infect Dis. 2004;190:879–885. [PubMed] 20. Katz MH, Schwarcz SK, Kellogg TA, et al. Impact of highly active antiretroviral treatment on HIV seroincidence among men who have sex with men: San Francisco. Am J Public Health. 2002;92:388–394. [PubMed] 21. Dukers NH, Spaargaren J, Geskus RB, et al. HIV incidence on the increase among homosexual men attending an Amsterdam sexually transmitted disease clinic: using a novel approach for detecting recent infections. AIDS. 2002;16:F19–F24. [PubMed] 22. Cohen MS, Gay C, Kashuba AD, et al. Narrative review: antiretroviral therapy to prevent the sexual transmission of HIV-1. Ann Intern Med. 2007;146:591–601. [PubMed] 23.
Garcia-Lerma JG, Otten RA, Qari SH, et al. Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. PLoS Med. 2008;5:e28. [PubMed]
This study evaluating the efficacy of various ART regimens and doses to prevent HIV transmission using the repeat-exposure macaques model found that two doses of ART given before and after exposure prevented transmission in all six animals studied. 24. Subbarao S, Ramos A, Kim C, et al. Direct stringency comparison of two macaque models (single-high vs. repeat-low) for mucosal HIV transmission using an identical anti-HIV chemoprophylaxis intervention. J Med Primatol. 2007;36:238–243. [PubMed] 25.
Sun Z, Denton PW, Estes JD, et al. Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1. J Exp Med. 2007;204:705–714. [PubMed]
This initial report of a novel murine model demonstrated the ability to infect humanized mice with HIV following a single intrarectal exposure. 26.
Denton PW, Estes JD, Sun Z, et al. Antiretroviral pre-exposure prophylaxis prevents vaginal transmission of HIV-1 in humanized BLT mice. PLoS Med. 2008;5:e16. [PubMed]
This report demonstrated the ability to infect humanized mice with HIV via intravaginal exposure and found that the daily administration of intraperitoneal emtricitabine and tenofovir prevented HIV transmission in all five mice that were administered ART 27. Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. N Engl J Med. 1997;337:1485–1490. [PubMed] 28. Panlilio AL, Cardo DM, Grohskopf LA, et al. Updated US Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep. 2005;54((RR-9)):1–17. [PubMed]
29. Martin NV, Almeda J, Casabona J. Effectiveness and safety of HIV post-exposure prophylaxis after sexual, injecting-drug-use or other non-occupational exposure [protocol] Cochrane Database of Systematic Reviews. 2005;2:CD005273.
30. Smith DK, Grohskopf LA, Black RJ, et al. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: recommendations from the U.S. Department of Health and Human Services. MMWR Recomm Rep. 2005;54((RR-2)):1–20. [PubMed] 31. Roland ME, Neilands TB, Krone MR, et al. Seroconversion following nonoccupational postexposure prophylaxis against HIV. Clin Infect Dis. 2005;41:1507–1513. [PubMed]
32. Kindrick A, Tang H, Sterkenberg C, et al. HIV post-exposure prophylaxis following sexual exposure is started too late for optimal benefit; Presented at the 13th Conference on Retroviruses and Opportunistic Infections; Denver, CO: [February 5–8, 2006].
33. Poynten IM, Smith DE, Cooper DA, et al. The public health impact of widespread availability of nonoccupational postexposure prophylaxis against HIV. HIV Med. 2007;8:374–381. [PubMed] 34. Quirino T, Niero F, Ricci E, et al. HAART tolerability: post-exposure prophylaxis in healthcare workers versus treatment in HIV-infected patients. Antivir Ther. 2000;5:195–197. [PubMed] 35. Bassett IV, Freedberg KA, Walensky RP. Two drugs or three? Balancing efficacy, toxicity, and resistance in postexposure prophylaxis for occupational exposure to HIV. Clin Infect Dis. 2004;39:395–401. [PubMed] 36. Ippolito G, Puro V. Zidovudine toxicity in uninfected healthcare workers. Italian Registry of Antiretroviral Prophylaxis. Am J Med. 1997;102:58–62. [PubMed] 37. Wang SA, Panlilio AL, Doi PA, et al. Experience of healthcare workers taking postexposure prophylaxis after occupational HIV exposures: findings of the HIV Postexposure Prophylaxis Registry. Infect Control Hosp Epidemiol. 2000;21:780–785. [PubMed] 38. Puro V, De Carli G, Orchi N, et al. Short-term adverse effects from and discontinuation of antiretroviral post-exposure prophylaxis. J Biol Regul Homeost Agents. 2001;15:238–242. [PubMed] 39. Sonder GJ, van den Hoek A, et al. Trends in HIV postexposure prophylaxis prescription and compliance after sexual exposure in Amsterdam; 2000–2004. Sex Transm Dis. 2007;34:288–293. [PubMed] 40. Mayer KH, Mimiaga MJ, Cohen D, et al. Tenofovir DF plus lamivudine or emtricitabine for nonoccupational postexposure prophylaxis (NPEP) in a Boston community health center. J Acquir Immune Defic Syndr. 2008;47:494–499. [PubMed] 41. Kahn JO, Martin JN, Roland ME, et al. Feasibility of postexposure prophylaxis (PEP) against human immunodeficiency virus infection after sexual or injection drug use exposure: the San Francisco PEP Study. J Infect Dis. 2001;183:707–714. [PubMed] 42. Winston A, McAllister J, Amin J, et al. The use of a triple nucleoside-nucleotide regimen for nonoccupational HIV post-exposure prophylaxis. HIV Med. 2005;6:191–197. [PubMed] 43. Wiebe ER, Comay SE, McGregor M, Ducceschi S. Offering HIV prophylaxis to people who have been sexually assaulted: 16 months’ experience in a sexual assault service. CMAJ. 2000;162:641–645. [PMC free article] [PubMed] 44. Vernazza PL, Troiani L, Flepp MJ, et al. Potent antiretroviral treatment of HIV-infection results in suppression of the seminal shedding of HIV. The Swiss HIV Cohort Study. AIDS. 2000;14:117–121. [PubMed] 45. Cu-Uvin S, Snyder B, Harwell JI, et al. Association between paired plasma and cervicovaginal lavage fluid HIV-1 RNA levels during 36 months. J Acquir Immune Defic Syndr. 2006;42:584–587. [PubMed] 46. Kotler DP, Shimada T, Snow G, et al. Effect of combination antiretroviral therapy upon rectal mucosal HIV RNA burden and mononuclear cell apoptosis. AIDS. 1998;12:597–604. [PubMed] 47.
Graham SM, Holte SE, Peshu NM, et al. Initiation of antiretroviral therapy leads to a rapid decline in cervical and vaginal HIV-1 shedding. AIDS. 2007;21:501–507. [PubMed]
A prospective study of antiretroviral native women that demonstrated a rapid and concurrent decline in HIV RNA levels in plasma and cervicovaginal secretions following ART initiation.
48. Reddy S, Troiani L, Kim J, et al. Differential phosphorylation of zidovudine and lamivudine between semen and blood mononuclear cells in HIV-1 infected men; Presented at the 10th Conference on Retroviruses and Opportunistic Infections; Boston, MA: [February 10–14, 2003].
Dumond JB, Yeh RF, Patterson KB, et al. Antiretroviral drug exposure in the female genital tract: implications for oral pre- and post-exposure prophylaxis. AIDS. 2007;21:1899–1907. [PubMed]
Pharmacokinetic study that measured first dose and steady-state concentrations of 11 antiretroviral agents in the blood plasma and cervicovaginal secretions of women and concluded that certain ART agents make more ideal candidates for pre- and postexposure prevention based on penetration into the genital tract. 50. Vourvahis M, Tappouni HL, Patterson KB, et al. The pharmacokinetics and viral activity of tenofovir in the male genital tract. J Acquir Immune Defic Syndr. 2008;47:329–333. [PMC free article] [PubMed]
Dumond J, Patterson K, Pecha A, et al. Maraviroc (MRV) genital tract (GT) fluid and tissue pharmacokinetics (PK) in healthy female volunteers: implications for pre- or postexposure prophylaxis (PrEP or PEP); Presented at the 15th Conference on Retroviruses and Opportunistic Infections; Boston, MA: [February 3–6, 2008].
A detailed analysis on plasma and genital tract pharmacokinetics of the new CCR5 inhibitor, maraviroc. The study found that cervicovaginal concentrations of maraviroc achieved or exceeded plasma concentrations after a single dose and were the highest concentrations in genital secretions compared with all other currently available antiretrovirals.
52. Vourvahis M, Tappouni H, Patterson K, et al. A pharmacologic basis for the use of tenofovir in pre- and post-exposure prophylaxis: intra and extracellular genital tract pharmacokinetics and pharmacodynamics from first dose to steady state in HIV-1 infected men and women [abstract 569]; Presented at the 13th Annual Conference on Retroviruses and Opportunistic Infections; Denver, CO: [February 5–8, 2006].
53. Lederman MM, Veazey RS, Offord R, et al. Prevention of vaginal SHIV transmission in rhesus macaques through inhibition of CCR5. Science. 2004;306:485–487. [PubMed] 54. Van Rompay KK, Schmidt KA, Lawson JR, et al. Topical administration of low-dose tenofovir disoproxil fumarate to protect infant macaques against multiple oral exposures of low doses of simian immunodeficiency virus. J Infect Dis. 2002;186:1508–1513. [PubMed] 55. Subbarao S, Otten RA, Ramos A, et al. Chemoprophylaxis with tenofovir disoproxil fumarate provided partial protection against infection with simian human immunodeficiency virus in macaques given multiple virus challenges. J Infect Dis. 2006;194:904–911. [PubMed]
56. Garcia-Lerma J, Otten R, Qari S, et al. Prevention of rectal SHIV transmission in macaques by tenofovir/FTC combination; Presented at the 13th Annual Conference on Retroviruses and Opportunistic Infections; Denver, CO: [February 5–8, 2006].
57. Magierowska M, Bernardin F, Garg S, et al. Highly uneven distribution of tenofovir-selected simian immunodeficiency virus in different anatomical sites of rhesus macaques. J Virol. 2004;78:2434–2444. [PMC free article] [PubMed]
58. Smith D, Kebaabetswe P, Disasi K, et al. Antiretroviral resistance is not an important risk of the oral tenofovir prophylaxis trial in Botswana: a simple mathematical modelling approach; Presented at the XVI International AIDS Conference; Toronto, Canada: [August 13–18, 2006].
62. Peterson L, Taylor D, Roddy R, et al. Tenofovir disoproxil fumarate for prevention of HIV infection in women: a phase 2, double-blind, randomized, placebo-controlled trial. PLoS Clin Trials. 2007;2:e27. [PMC free article] [PubMed]
63. Costello D. AIDS pill as party drug? Los Angeles Times. 2005 Dec 19;:F1.
64. Cohen J. Protect or disinhibit? New York Times. 2006 Jan 22;:12.
65. Kellerman SE, Hutchinson AB, Begley EB, et al. Knowledge and use of HIV pre-exposure prophylaxis among attendees of minority gay pride events, 2004. J Acquir Immune Defic Syndr. 2006;43:376–377. [PubMed] 66.
Mayer KH, Maslankowski L, Gai F, et al. Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS. 2006;20:543–551. [PubMed]
A safety and efficacy trial of tenofovir vaginal gel, which demonstrated that the 1% tenofovir formulation administered twice daily was well tolerated. The study failed to detect any new resistance mutations following a 2-week course of tenofovir vaginal gel.
67. Schwartz J, Kashuba A, Rezk N, et al. Presented at Microbicides. New Delhi, India: 2008. [February 24–27, 2008]. Preliminary results from a pharmacokinetic study of the candidate vaginal microbicide agent 1% tenofovir gel.
68. Blower SM, Gershengorn HB, Grant RM. A tale of two futures: HIV and antiretroviral therapy in San Francisco. Science. 2000;287:650–654. [PubMed] 69. Law MG, Prestage G, Grulich A, et al. Modelling the effect of combination antiretroviral treatments on HIV incidence. AIDS. 2001;15:1287–1294. [PubMed] 70. Velasco-Hernandez JX, Gershengorn HB, Blower SM. Could widespread use of combination antiretroviral therapy eradicate HIV epidemics? Lancet Infect Dis. 2002;2:487–493. [PubMed] 71. Abbas UL, Anderson RM, Mellors JW. Potential impact of antiretroviral chemoprophylaxis on HIV-1 transmission in resource–limited settings. PLoS ONE. 2007;2:e875. [PMC free article] [PubMed] 72. Shoptaw S, Rotheram-Fuller E, Landovitz RJ, et al. Nonoccupational post exposure prophylaxis as a biobehavioral HIV-prevention intervention. AIDS Care. 2007:1–6. [PubMed]
73. Grulich A, Jin FY, Prestage G, et al. Previous use of nonoccupational post exposure prophylaxis against HIV (NPEP) and subsequent HIV infection in homosexual men: data from the HIM cohort; Presented at the XVI International AIDS Conference; Toronto, Canada: [August 13–18, 2006].
74. Golub SA, Rosenthal L, Cohen DE, Mayer KH. Determinants of high-risk sexual behavior during post-exposure prophylaxis to prevent HIV infection. AIDS Behav. 2007 (Epub ahead of print) [PubMed] 75. Martin JN, Roland ME, Torsten BN, et al. Use of postexposure prophylaxis against HIV infection following sexual exposure does not lead to increases in high-risk behavior. AIDS. 2004;18:787–792. [PubMed] 76. Kalichman SC. Post-exposure prophylaxis for HIV infection in gay and bisexual men. Implications for the future of HIV prevention. Am J Prev Med. 1998;15:120–127. [PubMed] 77. Pilcher CD, Price MA, Hoffman IF, et al. Frequent detection of acute primary HIV infection in men in Malawi. AIDS. 2004;18:517–524. [PubMed] 78. Fiscus SA, Pilcher CD, Miller WC, et al. Rapid, real-time detection of acute HIV infection in patients in Africa. J Infect Dis. 2007;195:416–424. [PubMed] 79. Bjorn G. Swiss stance on HIV transmission sparks concern. Nat Med. 2008;14:227. [PubMed]