New Paradigms in HIV Prevention

The recent International AIDS Conference held in Washington highlighted new paradigms in HIV prevention. The biennial meeting brought more than 20,000 attendees together to focus on the political and social – as well as the clinical – aspects of the HIV/AIDS epidemic.

A major discussion topic was the new approach to HIV prevention. Back in the early 1980s, "safe sex" via condoms and abstinence was the focus of prevention strategies. In 2006, the Centers for Disease Control and Prevention recommended routine testing for everyone, in order to broaden the potential for both treatment and prevention (MMWR 2006;55(RR-14);1-17). But in the past 3-4 years, we’ve expanded the concept of prevention in the following three ways:

• Verbal consent. In July, Massachusetts became the 49th state to stop requiring written consent for HIV testing. Other states have done the same over the last 18-24 months. Now the test is explained to the patient, and the patient can simply agree verbally to be tested for HIV, without having to sign a form. We believe that’s a significant step forward, because the requirement for a signature made HIV testing different from any other medical test, which often scared patients and resulted in their reluctance to be tested.

• Treatment as prevention. In August 2011, the landmark HIV Prevention Trial 052 (HPTN 052) showed that early antiviral therapy in HIV-infected individuals who were in serodiscordant sexual relationships reduced transmission to their uninfected partners by 96% (N. Engl. J. Med. 2011;365:493-505). This means that now, part of the clinical decision about starting treatment involves consideration of the patient’s sexual contacts and their protection as well.

There is still concern about the side effects (such as insomnia, gastrointestinal problems, and bone demineralization) of antiretrovirals, as well as uncertainty about long-term adherence when treatment is started early. However, the new data on transmission have shifted the risk/benefit equation in favor of treating more people. In HPTN 052, treatment was started at CD4 counts of 350-550 cells per mcL. Now, many experts advocate starting HIV-infected individuals at T cell counts of 500 or greater, for both improved outcome in the individual and reduction in the risk of HIV transmission.

• Prophylaxis as prevention. With the approval of the combination emtricitabine and tenofovir disoproxil fumarate (Truvada) for pre-exposure prophylaxis, we now have the option of not only treating the HIV-infected partner in serodiscordant couples, but also prophylaxing the uninfected partner in order to prevent transmission.

To do this, the individual must be tested and prove to be HIV negative prior to starting on pre-exposure prophylaxis. Regular testing must also be done every 3-6 months thereafter for as long as the person is taking Truvada. Such testing is necessary because Truvada (which comprises two reverse transcriptase inhibitors) does not sufficiently suppress viral replication by itself, and must be used in combination with antiretrovirals of other classes in the treatment of HIV-infected individuals. If a person were to become HIV infected while taking only Truvada without other classes of antiretrovirals, there is a high risk for the development of resistance as a result of mutations in the replicating virus.

Of course, it could be argued that it is more ethical to treat the person who actually has the disease than to subject an uninfected person to potential antiretroviral toxicity. However, consider the following case I saw recently: A pregnant woman said that her HIV-infected partner was taking his medication, but the partner’s physician said he hadn\'t seen the patient in many months and didn’t know if he was still taking the antiretrovirals. The woman was in labor, and said she’d had sex with the man recently. If there had been time, we would have started her on nevirapine and AZT (zidovudine) prior to delivery. But in this case, she delivered too quickly. So we put the infant on antiretrovirals and tested the mother a month later. She was negative, so we were able to take the infant off the drugs.

There are many examples like this, in which the real world doesn’t quite line up with what we try to achieve through research and guidelines.

Of course, cost is a consideration as well. Insurance will typically cover some or all of the cost ($800-$1,000 per month) for antiretroviral treatment, but it’s too early to know whether that coverage will extend to prophylaxis. I think the cost will limit its use in that capacity, at least until reasonable clinical guidelines are developed to determine which patients would be best targeted with this approach. And just to note: Although Truvada is approved for treating those as young as age 12 years, thus far its use as prophylaxis is restricted to adults aged 18 years and older.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. He said he had no relevant financial disclosures.

The recent International AIDS Conference held in Washington highlighted new paradigms in HIV prevention. The biennial meeting brought more than 20,000 attendees together to focus on the political and social – as well as the clinical – aspects of the HIV/AIDS epidemic.

A major discussion topic was the new approach to HIV prevention. Back in the early 1980s, "safe sex" via condoms and abstinence was the focus of prevention strategies. In 2006, the Centers for Disease Control and Prevention recommended routine testing for everyone, in order to broaden the potential for both treatment and prevention (MMWR 2006;55(RR-14);1-17). But in the past 3-4 years, we’ve expanded the concept of prevention in the following three ways:

• Verbal consent. In July, Massachusetts became the 49th state to stop requiring written consent for HIV testing. Other states have done the same over the last 18-24 months. Now the test is explained to the patient, and the patient can simply agree verbally to be tested for HIV, without having to sign a form. We believe that’s a significant step forward, because the requirement for a signature made HIV testing different from any other medical test, which often scared patients and resulted in their reluctance to be tested.

• Treatment as prevention. In August 2011, the landmark HIV Prevention Trial 052 (HPTN 052) showed that early antiviral therapy in HIV-infected individuals who were in serodiscordant sexual relationships reduced transmission to their uninfected partners by 96% (N. Engl. J. Med. 2011;365:493-505). This means that now, part of the clinical decision about starting treatment involves consideration of the patient’s sexual contacts and their protection as well.

There is still concern about the side effects (such as insomnia, gastrointestinal problems, and bone demineralization) of antiretrovirals, as well as uncertainty about long-term adherence when treatment is started early. However, the new data on transmission have shifted the risk/benefit equation in favor of treating more people. In HPTN 052, treatment was started at CD4 counts of 350-550 cells per mcL. Now, many experts advocate starting HIV-infected individuals at T cell counts of 500 or greater, for both improved outcome in the individual and reduction in the risk of HIV transmission.

• Prophylaxis as prevention. With the approval of the combination emtricitabine and tenofovir disoproxil fumarate (Truvada) for pre-exposure prophylaxis, we now have the option of not only treating the HIV-infected partner in serodiscordant couples, but also prophylaxing the uninfected partner in order to prevent transmission.

To do this, the individual must be tested and prove to be HIV negative prior to starting on pre-exposure prophylaxis. Regular testing must also be done every 3-6 months thereafter for as long as the person is taking Truvada. Such testing is necessary because Truvada (which comprises two reverse transcriptase inhibitors) does not sufficiently suppress viral replication by itself, and must be used in combination with antiretrovirals of other classes in the treatment of HIV-infected individuals. If a person were to become HIV infected while taking only Truvada without other classes of antiretrovirals, there is a high risk for the development of resistance as a result of mutations in the replicating virus.

Of course, it could be argued that it is more ethical to treat the person who actually has the disease than to subject an uninfected person to potential antiretroviral toxicity. However, consider the following case I saw recently: A pregnant woman said that her HIV-infected partner was taking his medication, but the partner’s physician said he hadn\'t seen the patient in many months and didn’t know if he was still taking the antiretrovirals. The woman was in labor, and said she’d had sex with the man recently. If there had been time, we would have started her on nevirapine and AZT (zidovudine) prior to delivery. But in this case, she delivered too quickly. So we put the infant on antiretrovirals and tested the mother a month later. She was negative, so we were able to take the infant off the drugs.

There are many examples like this, in which the real world doesn’t quite line up with what we try to achieve through research and guidelines.

Of course, cost is a consideration as well. Insurance will typically cover some or all of the cost ($800-$1,000 per month) for antiretroviral treatment, but it’s too early to know whether that coverage will extend to prophylaxis. I think the cost will limit its use in that capacity, at least until reasonable clinical guidelines are developed to determine which patients would be best targeted with this approach. And just to note: Although Truvada is approved for treating those as young as age 12 years, thus far its use as prophylaxis is restricted to adults aged 18 years and older.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. He said he had no relevant financial disclosures.

The recent International AIDS Conference held in Washington highlighted new paradigms in HIV prevention. The biennial meeting brought more than 20,000 attendees together to focus on the political and social – as well as the clinical – aspects of the HIV/AIDS epidemic.

A major discussion topic was the new approach to HIV prevention. Back in the early 1980s, "safe sex" via condoms and abstinence was the focus of prevention strategies. In 2006, the Centers for Disease Control and Prevention recommended routine testing for everyone, in order to broaden the potential for both treatment and prevention (MMWR 2006;55(RR-14);1-17). But in the past 3-4 years, we’ve expanded the concept of prevention in the following three ways:

• Verbal consent. In July, Massachusetts became the 49th state to stop requiring written consent for HIV testing. Other states have done the same over the last 18-24 months. Now the test is explained to the patient, and the patient can simply agree verbally to be tested for HIV, without having to sign a form. We believe that’s a significant step forward, because the requirement for a signature made HIV testing different from any other medical test, which often scared patients and resulted in their reluctance to be tested.

• Treatment as prevention. In August 2011, the landmark HIV Prevention Trial 052 (HPTN 052) showed that early antiviral therapy in HIV-infected individuals who were in serodiscordant sexual relationships reduced transmission to their uninfected partners by 96% (N. Engl. J. Med. 2011;365:493-505). This means that now, part of the clinical decision about starting treatment involves consideration of the patient’s sexual contacts and their protection as well.

There is still concern about the side effects (such as insomnia, gastrointestinal problems, and bone demineralization) of antiretrovirals, as well as uncertainty about long-term adherence when treatment is started early. However, the new data on transmission have shifted the risk/benefit equation in favor of treating more people. In HPTN 052, treatment was started at CD4 counts of 350-550 cells per mcL. Now, many experts advocate starting HIV-infected individuals at T cell counts of 500 or greater, for both improved outcome in the individual and reduction in the risk of HIV transmission.

• Prophylaxis as prevention. With the approval of the combination emtricitabine and tenofovir disoproxil fumarate (Truvada) for pre-exposure prophylaxis, we now have the option of not only treating the HIV-infected partner in serodiscordant couples, but also prophylaxing the uninfected partner in order to prevent transmission.

To do this, the individual must be tested and prove to be HIV negative prior to starting on pre-exposure prophylaxis. Regular testing must also be done every 3-6 months thereafter for as long as the person is taking Truvada. Such testing is necessary because Truvada (which comprises two reverse transcriptase inhibitors) does not sufficiently suppress viral replication by itself, and must be used in combination with antiretrovirals of other classes in the treatment of HIV-infected individuals. If a person were to become HIV infected while taking only Truvada without other classes of antiretrovirals, there is a high risk for the development of resistance as a result of mutations in the replicating virus.

Of course, it could be argued that it is more ethical to treat the person who actually has the disease than to subject an uninfected person to potential antiretroviral toxicity. However, consider the following case I saw recently: A pregnant woman said that her HIV-infected partner was taking his medication, but the partner’s physician said he hadn\'t seen the patient in many months and didn’t know if he was still taking the antiretrovirals. The woman was in labor, and said she’d had sex with the man recently. If there had been time, we would have started her on nevirapine and AZT (zidovudine) prior to delivery. But in this case, she delivered too quickly. So we put the infant on antiretrovirals and tested the mother a month later. She was negative, so we were able to take the infant off the drugs.

There are many examples like this, in which the real world doesn’t quite line up with what we try to achieve through research and guidelines.

Of course, cost is a consideration as well. Insurance will typically cover some or all of the cost ($800-$1,000 per month) for antiretroviral treatment, but it’s too early to know whether that coverage will extend to prophylaxis. I think the cost will limit its use in that capacity, at least until reasonable clinical guidelines are developed to determine which patients would be best targeted with this approach. And just to note: Although Truvada is approved for treating those as young as age 12 years, thus far its use as prophylaxis is restricted to adults aged 18 years and older.

Dr. Pelton is chief of pediatric infectious disease and coordinator of the maternal-child HIV program at Boston Medical Center. He said he had no relevant financial disclosures.