Literature Commentary by Dr. John G. Bartlett -- HIV Epidemiology, Nov '07
Literature Commentary by Dr. John G. Bartlett -- HIV Epidemiology, Nov '07
Cohen MS, Gay C, Kashuba AD, Blower S, Paxton L. Narrative review: Antiretroviral therapy to prevent the sexual transmission of HIV-1. Ann Intern Med. 2007;146:591-601. The authors address the methods of preventing HIV infection, and discuss the high rates of new infections (4.1 million incident cases in the world in 2005), the lack of a vaccine, and the unlikely prospect of a vaccine in the near future.
Methods: The authors conducted a literature review based on their search of the Cochrane Library and PubMed databases.
Nonoccupational postexposure prophylaxis (nPEP): Several prospective and retrospective reports focus on the use of antiretroviral drugs (ARVs) in the context of nPEP. The reports include 4 prospective studies and 3 retrospective analyses. To date there have been 9 failures, but 7 of these came from 1 study. The available data from these reports is summarized in Table 1 , which does not permit any conclusions.
ARVs to reduce viral load in genital secretions: Logic dictates that transmission of HIV by the host or susceptibility by the partner is presumably affected by the concentrations in genital secretions. Data on this point have been collected from a number of studies, and several conclusions have been drawn: the concentration of ARVs in genital secretions is inversely related to protein binding and the affinity for albumin and alpha 1-acid glycoprotein. The available data show that high concentrations are achieved by most nucleoside reverse transcriptase inhibitors (NRTIs), but not by stavudine (d4T); and relatively poor penetration is achieved by protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). The data are summarized in Table 2 , which provides the drug concentrations in male and female genital tract secretions relative to plasma concentrations.
Treatment of HIV infection: There are a number of evolving studies in Africa involving discordant couples that are designed to determine the impact of treatment vs no treatment on rates of seroconversion. These studies show an impressive number of patients and an impressive outcome, with an 80%-98% reduction in transmission to partners of highly active antiretroviral therapy (HAART) recipients vs control. These data are summarized in Table 3 .
There are also a number of reports dealing with population-based studies in which there is an assumption that a reduction in the number of new cases is attributed to the availability of ARVs in the infected population, as reported from San Francisco and from Taiwan. However, others have reported that rates of HIV infection among men who have sex with men (MSM) have actually increased, suggesting that this may be due to an increase in high-risk behavior. This impression is supported by an increased rate of other sexually transmitted diseases (STDs), as well as an increase in the transmission of resistant strains.
Preexposure prophylaxis (PREP): Nearly all PREP studies utilize oral tenofovir (TDF) or TDF/emtricitabine (FTC). These studies are done in a diverse array of high-risk seronegative patients in Botswana, Peru, Thailand, and the United States. Preliminary data in rhesus macaques provide support for this tactic. To date, 1 study has been completed with 936 high-risk women in Cameroon, Ghana, and Nigeria; this showed no serious side effects in the TDF recipients, and the rate of transmission was 2 events in TDF recipients compared with 6 in the control arm.
Treatment and counseling during acute HIV infection: The more recent work, in large part by the author of the review article, has shown that the early stage of HIV infection is associated with high levels of HIV viremia prior to seroconversion and extremely high levels of the virus in genital secretions. This may account for up to 50% of sexual transmissions. The suggestion is that targeting therapy to such highly infectious persons might have an important impact on disease transmission. It should be noted that this is a debated conclusion.
Conclusions: The author acknowledges that not all of the interventions have been reviewed, but perhaps the major ones have. It is also acknowledged that HAART will have the potential benefit of reducing transmission, but the potential risk of a much more prolonged period of contagion.
Cohen MS, Gay C, Kashuba AD, Blower S, Paxton L. Narrative review: Antiretroviral therapy to prevent the sexual transmission of HIV-1. Ann Intern Med. 2007;146:591-601. The authors address the methods of preventing HIV infection, and discuss the high rates of new infections (4.1 million incident cases in the world in 2005), the lack of a vaccine, and the unlikely prospect of a vaccine in the near future.
Methods: The authors conducted a literature review based on their search of the Cochrane Library and PubMed databases.
Nonoccupational postexposure prophylaxis (nPEP): Several prospective and retrospective reports focus on the use of antiretroviral drugs (ARVs) in the context of nPEP. The reports include 4 prospective studies and 3 retrospective analyses. To date there have been 9 failures, but 7 of these came from 1 study. The available data from these reports is summarized in Table 1 , which does not permit any conclusions.
ARVs to reduce viral load in genital secretions: Logic dictates that transmission of HIV by the host or susceptibility by the partner is presumably affected by the concentrations in genital secretions. Data on this point have been collected from a number of studies, and several conclusions have been drawn: the concentration of ARVs in genital secretions is inversely related to protein binding and the affinity for albumin and alpha 1-acid glycoprotein. The available data show that high concentrations are achieved by most nucleoside reverse transcriptase inhibitors (NRTIs), but not by stavudine (d4T); and relatively poor penetration is achieved by protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). The data are summarized in Table 2 , which provides the drug concentrations in male and female genital tract secretions relative to plasma concentrations.
Treatment of HIV infection: There are a number of evolving studies in Africa involving discordant couples that are designed to determine the impact of treatment vs no treatment on rates of seroconversion. These studies show an impressive number of patients and an impressive outcome, with an 80%-98% reduction in transmission to partners of highly active antiretroviral therapy (HAART) recipients vs control. These data are summarized in Table 3 .
There are also a number of reports dealing with population-based studies in which there is an assumption that a reduction in the number of new cases is attributed to the availability of ARVs in the infected population, as reported from San Francisco and from Taiwan. However, others have reported that rates of HIV infection among men who have sex with men (MSM) have actually increased, suggesting that this may be due to an increase in high-risk behavior. This impression is supported by an increased rate of other sexually transmitted diseases (STDs), as well as an increase in the transmission of resistant strains.
Preexposure prophylaxis (PREP): Nearly all PREP studies utilize oral tenofovir (TDF) or TDF/emtricitabine (FTC). These studies are done in a diverse array of high-risk seronegative patients in Botswana, Peru, Thailand, and the United States. Preliminary data in rhesus macaques provide support for this tactic. To date, 1 study has been completed with 936 high-risk women in Cameroon, Ghana, and Nigeria; this showed no serious side effects in the TDF recipients, and the rate of transmission was 2 events in TDF recipients compared with 6 in the control arm.
Treatment and counseling during acute HIV infection: The more recent work, in large part by the author of the review article, has shown that the early stage of HIV infection is associated with high levels of HIV viremia prior to seroconversion and extremely high levels of the virus in genital secretions. This may account for up to 50% of sexual transmissions. The suggestion is that targeting therapy to such highly infectious persons might have an important impact on disease transmission. It should be noted that this is a debated conclusion.
Conclusions: The author acknowledges that not all of the interventions have been reviewed, but perhaps the major ones have. It is also acknowledged that HAART will have the potential benefit of reducing transmission, but the potential risk of a much more prolonged period of contagion.
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