Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 338).
1. Henry K, Chinnock BJ, Quinn RP, et al. Concurrent zidovudine levels in semen and serum determined by radioimmunoassay in patients with AIDS or AIDS-related complex. JAMA. 1988;259:3023–3026. [PubMed] 2.
Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide,for the prevention of HIV infection in women. Science. 2010;329:1168–1174. [PubMed]This study is the first to report the results of a clinical trial demonstrating the effectiveness and safety of a 1% vaginal gel formulation of TDF for the prevention of HIV acquisition in women. Results show that the gel reduces HIV acquisition by an estimated 39% overall and by 54% in women with high gel adherence. 3.
Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363:2587–2599. [PubMed]This study is the first to report the results of a clinical trial demonstrating the efficacy of oral preprophylactic effect (iPREX) in preventing HIV among MSM in Asia and Africa. More information is needed to evaluate possible subclinical effects such as low-level drug resistance as well as potential adjustments in HIV risk behavior among users. 4. Michael NL. Oral preexposure prophylaxis for HIV: another arrow in the quiver? N Engl J Med. 2010;363:2663–2665. [PubMed] 5. Nicol MR, Kashuba AD. Pharmacologic opportunities for HIV prevention. Clin Pharmacol Ther. 2010;88:598–609. [PubMed] 6. 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] 7. Dumond JB, Patterson KB, Pecha AL, et al. Maraviroc concentrates in the cervicovaginal fluid and vaginal tissue of HIV-negative women. J Acquir Immune Defic Syndr. 2009;51:546–553. [PMC free article] [PubMed]
8. Patterson K, Prince H, Kraft E, et al. Exposure of extracellular and intracellular tenofovirandemtricitabine in mucosal tissues after a single fixed dose of TDC/ FTC: implications for preexposure HIV prophylaxis (PrEP); 18th International AIDS conference; Vienna, Austria. 2010.
9. 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] 10. Dumond JB, Reddy YS, Troiani L, et al. Differential extracellular and intracellular concentrations of zidovudine and lamivudine in semen and plasma of HIV-1-infected men. J Acquir Immune Defic Syndr. 2008;48:156–162. [PMC free article] [PubMed]
11. Bonora S, D’Avolio A, Simiele M, et al. Steady-state raltegravir penetration in seminal plasma of healthy volunteers; 17th Conference on Retroviruses and Opportunistic Infections; San Francisco, California. 2010.
12. Brown K, Patterson K, Malone S, et al. Antiretrovirals for prevention: maraviroc exposure in the semen and rectal tissue of healthy male volunteers after single and multiple dosing; 17th Conference on Retroviruses and Opportunistic Infections; San Francisco, California. 2010.
13. Brown KC, Patterson KB, Jennings SH, et al. Antiretrovirals for HIV prevention: darunavir + low dose ritonavir and etravirine exposure in the rectal tissue and seminal plasma of healthy male volunteers after single and multiple dosing; 18th Annual Conference on Retroviruses and Opportunistic Infections; Boston, Massachusetts. 2011.
14. Fletcher P, Harman S, Azijn H, et al. Inhibition of human immunodeficiency virus type 1 infection by the candidate microbicide dapivirine, a nonnucleoside reverse transcriptase inhibitor. Antimicrob Agents Chemother. 2009;53:487–495. [PMC free article] [PubMed]
15. Brown L, Poole C, Patterson K, Cohen M. Variability in female genital tract shedding and plasma viral loads: a systematic review; 17th International AIDS Conference; 3–8 August 2008; Mexico City.
16. Chan DJ. Pathophysiology of HIV-1 in semen: current evidence for compartmentalization and penetration by antiretroviral drugs. Current HIV Res. 2005;3:207–222. [PubMed] 17. Le Tortorec A, Dejucq-Rainsford N. HIV infection in the male genital tract: consequences for sexual transmission and reproduction. Int J Androl. 2010;33:e98–e108. [PMC free article] [PubMed] 18. Diem K, Nickle DC, Motoshige A, et al. Male genital tract compartmentalization of human immunodeficiency virus type 1 (HIV) AIDS Res Hum Retroviruses. 2008;24:561–571. [PubMed] 19. Philpott S, Burger H, Tsoukas C, et al. Human immunodeficiency virus type 1 genomic RNA sequences in the female genital tract and blood: compartmentalization and intrapatient recombination. J Virol. 2005;79:353–363. [PMC free article] [PubMed] 20.
Cu-Uvin S, DeLong AK, Venkatesh KK, et al. Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load. AIDS. 2010;24:2489–2497. [PubMed]This study determines patterns of genital tract HIV-1-RNA shedding over time among women with suppressed plasma viral load on ART. 21. Sheth PM, Kovacs C, Kemal KS, et al. Persistent HIV RNA shedding in semen despite effective antiretroviral therapy. AIDS. 2009;23:2050–2053. [PubMed] 22.
Paredes R, Lalama CM, Ribaudo HJ, et al. Preexisting minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. J Infect Dis. 2010;201:662–671. [PubMed]This study of the relationship between minority drug-resistant human HIV-1 and virologic failure in treated patients finds that in adherent patients, pre-existing minority Y181C mutants more than triple the risk of virologic failure of first-line efavirenz-based ART. 23. Johnson JA, Li JF, Wei X, et al. Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associate with reduced treatment efficacy. PLoS Med. 2008;5:e158. [PMC free article] [PubMed] 24. Metzner KJ, Rauch P, von Wyl V, et al. Efficient suppression of minority drug-resistant HIV type 1 (HIV-1) variants present at primary HIV-1 infection by ritonavir-boosted protease inhibitor-containing antiretroviral therapy. J Infect Dis. 2010;201:1063–1071. [PubMed] 25. Toni TA, Asahchop EL, Moisi D, et al. Detection of human immunodeficiency virus (HIV) type 1 M184V and K103N minority variants in patients with primary HIV infection. Antimicrob Agents Chemother. 2009;53:1670–1672. [PMC free article] [PubMed] 26.
Anderson JA, Ping LH, Dibben O, et al. HIV-1 populations in semen arise through multiple mechanisms. PLoS Pathog. 2010;6 e1001053. [PMC free article] [PubMed]This study compared HIV sequences in blood and semen using single gene amplification, a method that allows sensitive discrimination of these biological compartments. The results demonstrated that in some patient, blood and semen harbored similar viral variants, but that considerable divergence was possible. In addition, duplication of variants was observed in semen isolates, emphasizing ongoing viral replication in a closed compartment. 27. Derdeyn CA, Decker JM, Bibollet-Ruche F, et al. Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission. Science. 2004;303:2019–2022. [PubMed] 28.
Harrison L, Castro H, Cane P, et al. The effect of transmitted HIV-1 drug resistance on pretherapy viral load. AIDS. 2010;24:1917–1922. [PubMed]In this study, the authors demonstrate detection of transmitted variants with drug resistance markers. They note that individuals infected with the M184 V/l variant had lower blood viral load, which they argue reflects a replication fitness cost associated with the mutation. 29. Murillo W, Paz-Bailey G, Morales S, et al. Transmitted drug resistance and type of infection in newly diagnosed HIV-1 individuals in Honduras. J Clin Virol. 2010;49:239–244. [PubMed] 30. Balode D, Westman M, Kolupajeva T, et al. Low prevalence of transmitted drug resistance among newly diagnosed HIV-1 patients in Latvia. J Med Virol. 2010;82:2013–2018. [PubMed] 31. Vercauteren J, Wensing AM, van de Vijver DA, et al. Transmission of drug-resistant HIV-1 is stabilizing in Europe. J Infect Dis. 2009;200:1503–1508. [PubMed] 32.
Eyawo O, de Walque D, Ford N, et al. HIV status in discordant couples in sub-Saharan Africa: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10:770–777. [PubMed]This systematic review finds that women are as likely as men to be the index partner in a discordant couple, highlighting the need to focus on both sexes in HIV prevention strategies. 33. Trask SA, Derdeyn CA, Fideli U, et al. Molecular epidemiology of human immunodeficiency virus type 1 transmission in a heterosexual cohort of discordant couples in Zambia. J Virol. 2002;76:397–405. [PMC free article] [PubMed] 34. 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;191:1402–1409. [PubMed] 35.
Gray R The contribution of HIV-discordant relationships to new HIV infections in Rakai, Uganda. AIDS. (in press) [PubMed]This research letter presented findings from a secondary analysis of the Rakai Cohort Study in which only a minority of new HIV infections was found to have occurred in the context of a stable HIV-discordant couple relationship. 36. 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] 37. Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med. 2000;342:921–929. [PubMed] 38. Operskalski EA, Stram DO, Busch MP, et al. Role of viral load in heterosexual transmission of human immunodeficiency virus type 1 by blood transfusion recipients. Transfusion Safety Study Group. Am J Epidemiol. 1997;146:655–661. [PubMed] 39. Pedraza MA, del Romero J, Roldan F, et al. Heterosexual transmission of HIV-1 is associated with high plasma viral load levels and a positive viral isolation in the infected partner. J Acquir Immune Defic Syndr. 1999;21:120–125. [PubMed] 40. 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] 41. Castilla J, del Romero G, 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] 42.
Del Romero J, Castilla J, Hernando V, et al. Combined antiretroviral treatment and heterosexual transmission of HIV-1: cross sectional and prospective cohort study. BMJ. 2010;340:c2205. [PubMed]This article reports findings from a prospective study of 424 serodiscordant couples and finds an HIV seroconversion rate of 0–0.0005 per unprotected intercourse among the 144 couples in which the index partner was on ART. This finding suggests that heterosexual infectivity of HIV-1 in treated individuals may be very low. 43. Donnell D, Baeten JM, Kiarie J, et al. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet. 2010;375:2092–2098. [PMC free article] [PubMed] 44. Hernando V, del Romero G, Garcia S, et al. Reducing sexual risk behavior among steady heterosexual serodiscordant couples in a testing and counseling program. Sex Transm Dis. 2009;36:621–628. [PubMed] 45. Melo MG, Santos BR, Lira RDC, et al. Sexual transmission of HIV-1 among serodiscordant couples in Porto Alegre, southern Brazil. Sex Transm Dis. 2008;35:912–915. [PubMed] 46. 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] 47. Reynolds SJ, Makumbi F, Nakigozi G, et al. HIV-1 transmission among HIV-1 discordant couples before and after the introduction of antiretroviral therapy. AIDS. 2011;25:473–477. [PMC free article] [PubMed]
48. Sullivan P, Kayitenkore K, Chomba E, et al. Reduction of HIV transmission risk and high risk sex while prescribed ART: results from discordant couples in Rwanda and Zambia; 16th Conference on Retroviruses and Opportunistic Infections; Montreal, Canada. 2009.
Wang L, Ge Z, Luo J, et al. HIV transmission risk among serodiscordant couples: a retrospective study of former plasma donors in Henan, China. J Acquir Immune Defic Syndr. 2010;55:232–238. [PubMed]This article reports findings from a prospective study of 1927 serodiscordant couples. Authors report an HIV incidence rate of 1.71 per 100 person-years in which transmission events are equally distributed among couples whose index case was receiving or was not receiving ART. 50. 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] 51.
Das M, Chu PL, Santos GM, et al. Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco. PLoS One. 2010;5:e11068. [PubMed]This study identified a positive association between decreases in total community viral load – measured as the sum of the most recent viral load of all reported HIV-positive individuals – and the era of expanded ART in San Francisco. 52. 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] 53. 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] 54. 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] 55. Lima VD, Johnston K, Hogg RS, et al. Expanded access to highly active antiretroviral therapy: a potentially powerful strategy to curb the growth of the HIV epidemic. J Infect Dis. 2008;198:59–67. [PubMed] 56. Montaner JS, Hogg R, Wood E, et al. The case for expanding access to highly active antiretroviral therapy to curb the growth of the HIV epidemic. Lancet. 2006;368:531–536. [PubMed] 57.
Montaner JS, Lima VD, Barrios R, et al. Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British Columbia, Canada: a population-based study. Lancet. 2010;376:532–539. [PubMed]Using mathematical models to analyze HIV surveillance data in British Columbia, the authors of this study claimed evidence of strong population-level associations among expanded ART coverage, decreased population viral load, and fewer annual HIV diagnoses between 1996 and 2009. 58. Shelton JD, Cohen M, Barnhart M, Hallett T. Is antiretroviral therapy modifying the HIV epidemic? Lancet. 2010;376:1824–1825. author reply 1825. [PubMed] 59.
Grulich AE, Wilson DP Is antiretroviral therapy modifying the HIV epidemic? Lancet. 2010;376:1824. author reply 1825. [PubMed]The authors point out the ecologic fallacy underlying the findings by Montaner et al. [57•] on the association between ART coverage and community HIV viral load. Safer injection practices among IDUs is also highlighted as a likely confounder that could lead to overestimation of the association between expanded ART on lowered HIV incidence in British Columbia. 60. Dukers NHTM, 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] 61. Stolte IG, Dukers NHTM, de Wit JBF, et al. Increase in sexually transmitted infections among homosexual men in Amsterdam in relation to HAART. Sex Transm Infect. 2001;77:184–186. [PMC free article] [PubMed] 62.
Jansen IA, Geskus RB, Davidovich U, et al. Ongoing HIV-1 transmission among men who have sex with men in Amsterdam: a 25-year prospective cohort study. AIDS. 2011;25:493–501. [PubMed]This cohort study reports ongoing HIV-1 transmission among MSM in Amsterdam, particularly following increases in sexual risk behavior from 1996 onwards. 63.
Jin F, Jansson J, Law M Per-contact probability of HIV transmission in homosexual men in Sydney during the era of HAART. AIDS. 2010;24:907–913. [PubMed]A longitudinal cohort study of homosexual men in Australia found little difference in the per-contact probability of HIV transmission before and after widespread uptake of ART in HIV-infected men. The authors hypothesize that untreated STIs or unprotected sex during acute infection may partially explain the persistence of transmission even with high ART coverage.
64. Lima V, Williams B, Hogg R, et al. Why the MSM-driven HIV epidemic is not slowing down even in the presence of HAART; 18th Conference on Retroviruses and Opportunistic Infections; Boston, Massachusetts. 2011.
65. Hall HI, Song R, Rhodes P, et al. Estimation of HIV incidence in the United States. JAMA. 2008;300:520–529. [PMC free article] [PubMed] 66.
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Pretorius C, Stover J, Bollinger L, et al. Evaluating the cost-effectiveness of preexposure prophylaxis (PrEP) and its impact on HIV-1 transmission in South Africa. PLoS One. 2010;5:e13646. [PubMed]This study models the potential impact of pre-exposure prophylaxis in averting new infections in South Africa and estimates a range in cost from $1 2 500 to $20 000 per infection averted, depending on the level of ART coverage and baseline incidence. 74.
Walensky RP, Paltiel AD, Losina E, et al. Test and treat DC: forecasting the impact of a comprehensive HIV strategy in Washington DC. Clin Infect Dis. 2010;51:392–400. [PubMed]This study applies a mathematical model to estimate the potential impact of an expanded HIV test and treat program in Washington, District of Columbia. The authors find that an intensive test and treat program – although expected to yield substantial benefits to individual patients – cannot be expected to stop the epidemic in Washington, District of Columbia, a finding that holds important implications for ongoing ‘test and treat’ strategies. 75.
Long EF, Brandeau ML, Owens DK The cost-effectiveness and population outcomes of expanded HIV screening and antiretroviral treatment in the United States. Ann Intern Med. 2010;153:778–789. [PubMed]This article applies a dynamic mathematical model to perform a cost-effectiveness model of expanded ART, HIV screening, and behavioral interventions. The authors suggest that expanded screening and treatment offers a substantial public health impact, but are insufficient to reduce the US HIV epidemic without substantial reductions in risk behavior. 77. Emery S, Neuhaus JA, Phillips AN, et al. 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. [PubMed]
78. Severe P, Pape J, Fitzgerald DW. A randomized clinical trial of early versus standard antiretroviral therapy for HIV-infected patients with a CD4 T cell count of 200–350 cells/ml (CIPRA HT 001); 49th Interscience Conference on Antimicrobial Agents and Chemotherapy; San Francisco, California. 2009.
79. Vernazza P, Hirschel B, Bernasconi E, Flepp M. HIV - infected patients under HAART without any other sexually transmitted infection do not transmit HIV by sexual intercourse. Bull Med Suisse. 2008;89:165–169.
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89. Hightow LB, MacDonald PD, Pilcher CD, et al. The unexpected movement of the HIV epidemic in the southeastern United States: transmission among college students. J Acquir Immune Defic Syndr. 2005;38:531–537. [PubMed] 90. Pettifor A, Macphail C, Corneli A, et al. Continued high risk sexual behavior following diagnosis with acute HIV infection in South Africa and Malawi: implications for prevention. AIDS Behav. (in press) [PMC free article] [PubMed]
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