Epidemiology of HIV
There have been three-quarters of a million persons reported with AIDS in the United States, and there have been more than one-third of a million deaths. About 8,000 children have been infected, more than half of whom have died.
Several important changes have occurred in the demographic profile of people with AIDS. There has been an increasing impact of the epidemic on minority groups in this country. Persons with AIDS have been gradually decreasing as a proportion of all HIV cases, with corresponding increases among Hispanic persons and also African-Americans. African-American and Hispanic persons taken together now account for about two-thirds of all persons recently reported with AIDS, and about 80% of all women recently reported with AIDS.
The proportion of cases in women is gradually increasing, and about 22% of all people reported with AIDS are women.
At the beginning of the epidemic , most of the cases that we talked about then were occurring in large cities in the Northeast and in the far West. But over time, the proportion of cases from those parts of the country have been gradually decreasing with increases in the Midwest and increases in the South. In contrast to cases in the Northeast and the far West, many of the cases in the South are occurring not just in major urban areas, but also in smaller cities and town. More than half of all AIDS cases reported from rural areas have been from Southern states.
HIV exposure categories. At the beginning of the AIDS epidemic, almost all the cases were in gay men and by 1985 about two-thirds of cases were among gay men. But that proportion has been decreasing with corresponding increases in injecting drug users and in persons infected through heterosexual contact.
In addition to these rather gradual changes in the face of the epidemic, which most likely reflect changes in behaviors, the last few years have brought us some very dramatic changes in AIDS morbidity and mortality, resulting from improved anti-retroviral therapy, and also the increasing use of prophylaxis to prevent specific opportunistic infections. Zovirax online
AIDS cases peaked in 1993 and have been gradually decreasing ever since then. AIDS deaths, which peaked in 1995, have been dropping at a great rate through 2006. Looking at reported AIDS cases, you can see an overall decrease of about 14% in a single year. You can see a bigger drop in AIDS cases among men than among women. A bigger drop among white persons than among blacks or Hispanics. A bigger drop among gay men than among injecting drug users or persons infected through heterosexual contact. Buy Generic Diflucan
This is a similar kind of depiction of the decrease in AIDS deaths over the same one year period. Here the overall drop is truly remarkable; 44%. But again, we see a greater effect in men, in whites, and in men who have had sex with men. There is another way to look at this as well. Some of you who have attended this course probably remember seeing slides like this which compare the leading causes of death for all young adults - defined here as 25 to 44 - in the United States. And I used to present the slide to make that point that HIV/AIDS in the mid-1990’s had become the leading cause of death for all young adults in this country. But now I can show you this remarkable decrease that’s really just happened over the last couple of years. In fact, it represents about a 64% decrease in deaths due to AIDS in these young adults in just a two-year period. So the overall news is really very good. We see decreases in AIDS incidences and deaths, but if we go back to our schematic and we think about it for a second, we realize that if mortality from AIDS is dropping faster than the incidence of AIDS, we are going to see an increase in the level of the water in this reservoir, or the prevalence of AIDS. In other words, there are going to be more infected people in the population. And in fact, that’s what’s happened. This is an estimate of the number of people with AIDS who are now living in the United States and you can see how it is continuing to increase over time. Lamisil onine
It’s obviously good news that more and more HIV infected people are living longer and longer, but at the same time we have to appreciate that this means that the number of people requiring care is also going up quite rapidly. Treating fungal infection
The news regarding AIDS in children is a lso good. As shown here, cases that result from mother-to-child transmission have decreased by about 43% from 1992 through 2006. Since we believe that the number of HIV-infected pregnant women has not decreased that much, these trends most likely reflect the use of anti-retroviral therapy in pregnant women and the subsequent reduction in the rate of perinatal transmission. CDC has been conducting sentinel surveillance to look specifically at the uses of zidovudine prophylaxis in HIV-infected mothers and their children. This slide shows you some data on HIV-infected mothers who gave birth in four sentinel states; in Louisiana, Michigan, New Jersey and South Carolina in the years ’93, ’95 and ’96. You can see that the proportion of infected women who are tested before they deliver has been increasing gradually over that time. Sixty-eight up to 81%. You can also see that the proportion of women who are offered zidovudine either in the prenatal period or during labor and delivery, has also increased quite substantially over this time. As has the proportion of infants who are given therapy during the neonatal period, from 5% up to about 75%. So that’s the good news. Buy Bactroban Cream
But the bad news on the slide, as shown down here, which is the proportion of women who don’t receive any prenatal care has essentially stayed the same over the same period. I think the message here is if you want to improve our prevention efforts in preventing perinatal transmission, one of the things we are going to have to emphasize would be the approach to try to get these women into care so we can offer them the benefits of anti-retroviral therapy. Treating herpes zoster infection
So far we’ve talked about all AIDS cases and all AIDS deaths, but I also want to look at how we’re doing in preventing specific opportunistic infections that occur in the HIV-infected persons. The study that I am going to cite here is called the “Adult Spectrum of Disease” project, or ASD which is a multi-center study that has been funded for several years by CDC in which basically chart reviews are done every six months on about 20,000 HIV-infected persons seen around the country. The slides are a little bit hard to read, but I’ll give you the main points. This first slide looks at the annual incidence of AIDS-defining opportunistic infections in homosexual men. And it’s limited to gay men who have a CD4 count below 200. Even though you probably can’t see all the numbers, the point is that there have been significant decreases in the incidence of all of these AIDS defining opportunistic infections in gay men from 1991 through ’96. However, if we look at a similar kind of slide that’s done for HIV-infected injecting drug users seen at the same facilities, we see a somewhat different picture. There have been significant decreases in some of the most important opportunistic infections, such as Pneumocystis pneumonia, which is shown here; such as tuberculosis which is shown here. But there has not been any significant reduction in the incidence of other severe infections, such as M. avium, cryptococcosis and toxoplasmosis. Augmentin antibiotic
So the question then is, why are we seeing this difference? Why are the gay men doing better than the injecting drug users? I think several reasons are apparent if we look a little bit more into the study. First of all, the gay men simply get more care. And again, these are people who are being seen at the same facilities, but yet the gay men are averaging about nine outpatient visits per year over this period versus six per year for the injecting drug users. If we look at the use of combination therapy, which for this study was defined as the use of two or more anti-retroviral drugs, you can see considerably higher rates of combination therapy in gay men than in injecting drug users. For example, in 2006 more than half the gay men were on combination therapy versus less than one-third of the injecting drug users. And another reason may be that gay men were more likely to receive recommended anti-microbial prophylaxis than injecting drug users. This slide shows you the example of medications that are recommended for prevention of disseminated M. avium infections, the medication is shown here. And you can see that the percent of gay men given this prophylaxis is considerably higher than for injecting drug users. Compliance was not measured in this study, but it certainly could be a contributing factor. Cephalexin Onlone
Now as you know, in addition to the opportunistic infections there are several malignancies that are considered to be AIDS defining in the HIV-infected person. The ASD study also gives us the opportunity to look at trends in these various malignancies over time. The incidence of Kaposi’s sarcoma, which is by far the most common AIDS defining malignancy, has actually been steadily decreasing for a number of years. But you can see it just very abruptly dropped in association with the use of highly active anti-retroviral therapy. It’s a little harder to see, but down here on the bottom in green, it shows trends in primary brain lymphomas and again we are seeing a significant decrease in incidence. What’s disturbing, I think, on this slide is the middle line. This line is showing you the annual incidence of non-Hodgkin’s lymphomas in these patients, and that has not decreased. It’s actually stayed quite constant over time.
It’s probably too early in the era of HAART to draw any conclusions about these trends, but I think our concern would be that perhaps as HIV-infected people start to live longer and longer, an increasing proportion of them may be developing lymphomas. Flagyl online
So far we’ve talked about the bottom part of that diagram that we started out with, AIDS cases and deaths. But now I want to talk more about the earlier part of the epidemic: HIV infection. What are the characteristics of newly infected persons, persons who haven’t yet developed AIDS and at what rate are they becoming infected? There are a number of different sources of information about HIV infection. Each of them gives us a different part of the picture. I think probably the best information about the characteristics of people who are HIV-infected but have not yet developed AIDS comes from the 25 states that have been conducting surveillance for HIV infection over the last couple of years. For these 25 states, this slide summarizes some of the characteristics of people reported with HIV infection but not AIDS and persons reported with AIDS. You can see that the persons reported with HIV infection are more likely to be women, they are more likely to be non-white, they are more likely to have been infected through heterosexual contact, and as you would expect, they are more likely to be young. So if you want a picture of what the AIDS epidemic is going to look like in a couple of years, this is it. Buy Generic Levaquin
The prevalence of HIV infection or the proportion of all people who are infected in different groups is probably measured by the anonymous clinic-based sero-surveys that are conducted around the country. This slide gives you an example of one of these surveys that’s done among gay men attending sexually transmitted disease clinics around the country. The height of the red bars shows you the prevalence of HIV infection. It does vary quite a bit. For example, on this slide, the low is Minneapolis where about 4% of these gay men attending STD clinics were infected, to a high of about 30% in Houston. But you don’t seen any particular trends by geographic area.
We also collect data on injecting drug users who are entering drug treatment centers around the country. Again, prevalence is reflected by the height of these red bars and here there is more geographic clustering. We see the highest prevalence in the Northeast and in the South, and relatively low rates of infection among injecting drug users along the West Coast. By testing people who make repeat visits to these facilities we can then estimate incidence. We can estimate the number of new infections that are occurring per 100 person years of follow-up. This slide shows you incidence data, the rate of new infection for people attending the STD clinics that I showed you early on. The incidence in gay men is shown here in orange and you can see in all of the study sites the incidence is quite a bit higher among gay men than among heterosexual men and women. Again, Houston stands out as having very high rates. I don’t actually know why that is. Myambutol online
We’ve also tried to do incidence studies for people making repeat visits to drug treatment centers and here the incidence seems to be quite low. Ranging from 0% per 100 person years in Los Angeles to about 1 per 100 person years in New York City. But if you think about it, this is a highly biased sample. These are people who are making repeat visits to a treatment center and they almost certainly are not representative of what’s going on out in the street. I’m going to come back in a couple of minutes to try to give you another approach to looking at incidence in this kind of population.
For the rest of the time, what I want to do is talk a little bit more about prevention and specifically how some recent advances in laboratory science can aid us in prevention both of progression from HIV infection to AIDS, which is referred to as secondary prevention. And also prevention of HIV infection itself, which is primary prevention. I hope that all of you have gotten the message that to prevent morbidity and mortality in HIV-infected people we have to find them. We have to identify them early in the course of their infection and we have to be able to refer them to treatment. One way we can do a better job of this is by the use of recently developed rapid tests for HIV antibody. Rapid tests typically can give us a preliminary screening result for HIV antibody in about 15 minutes. This slide shows you a number of test formats that have been developed. It shows you a number of relatively simple devices can be used for this purpose. Right now most of these tests are designed to be used on serum samples, but they are being adapted so that they can be used on whole blood and even on saliva and urine samples. The sensitivity and specificity of these rapid tests are comparable to our licensed enzyme immunoassays, or EIA’s. If a person tests negative on a rapid test we can tell them on the spot, “You aren’t infected.” Persons who have positive tests need to be told that this is a preliminary result and they will have to return to receive the confirmed result. Typically the results are confirmed with a Western Blot Assay. Unfortunately, at the moment there is only one licensed rapid test in the United States called the SUDS test. But there are literally dozens of them being used in other countries. CDC worked with investigators in Dallas Texas to look at the licensed rapid test, the SUDS test, in two kinds of facilities; at an anonymous test site and also at an STD clinic. Buy Sumycin online
I’m showing you the results from the STD clinic here. This shows you what was happening under standard protocol where an enzyme immunoassay was done and a patient was told to return in a couple of weeks to get the results, versus the rapid protocol. You can see that the proportion of people who received a negative result went up from 30% to 93% by using the rapid protocol. The proportion who could receive a positive result went up from 79% up to 97%. A survey was done of 255 patients who were attending these clinics to find out what they understood about it and whether they liked it or not. I think it’s quite interesting to see that about 90%, or more than 90% of the clients understood what this test was about and about 90% of them said they actually preferred receiving the results this way rather than in the conventional way. Initially counselors at these sites were quite apprehensive about using rapid tests, but a survey that was done a month after the rapid test was started indicated that most of these concerns were resolved. Counselors reported that some clients that had received preliminary positive results followed several weeks later by confirmed results, felt that this was a good way of breaking bad news in a more gentle way.
In addition to the publicly funded clinics there are a number of other test sites that could be looked at for the use of rapid HIV testing. I’ve listed a number of them here but the one I just want to bring to your attention is this one. The use of rapid testing to prevent perinatal transmission. As I indicated before, one of the reasons that we are not eliminating perinatal transmission is that we don’t find infected women before they go into labor. In settings where we have these women in labor and delivery who have not been tested before, we could consider the option of offering them rapid testing. It could be done in about 15 minutes. If the result is positive we can offer that woman treatment and we can often offer treatment to the newborn. If it turns out that the newborn is not infected we can stop therapy at that time. We hope that by indicating these many potential applications of rapid testing that we will encourage more manufacturers to seek FDA licensing of their products. Trimox 500mg
A second laboratory advance is the use of modified EIA tests to estimate HIV incidence. As I’ve tried to indicate, estimating HIV incidence is really a key element in evaluating primary prevention programs. But as I also indicated before, the way that we are doing it now is highly biased because we are relying on people who make repeated visits to a facility. To try to avoid this bias, Dr. Rob Janssen from CDC and a number of collaborators recently published a new approach to this problem. It’s been called several things, including the “Detuned Assay” which would probably fit at the Sun Valley “Detuned” meeting, but the official name is “The sensitive, less sensitive testing strategy.” As all of you know, what we normally want to do when we are doing a screening test is make it very very sensitive. We want to be able to detect people as early as possible following infection. But it’s also possible to intentionally make the assay less sensitive. If we do that, we can find individuals who are going to be positive by the very sensitive assay and negative by the less sensitive assay. Most likely these people are recently infected so the titer of antibody in their blood is increasing so that it can be detected by the sensitive test shown here, but it’s going to be missed by the less sensitive test. Vantin online
In the approach that Rob Janssen reported, he took a standard Abbot enzyme immunoassay and detuned it so that it would take four more months to document seroconversion than the standard assay. Persons in this period therefore are most likely recently infected. It’s then possible to use these results to model the incidence of HIV infection in a population that you screen with both the sensitive and the detuned assay. How well does it actually work? This slide looks at the results in two studies. One is a study of gay men in San Francisco and the other a national study of blood donors and it shows you the estimated incidence per 100 person years using the new testing strategy, versus what was actually observed in the two studies. I think you’ll agree, the results are remarkably close.
Based on this approach, the San Francisco Health Department has been using the detuned assay to try to look at the incidence of HIV infection seen in gay men in a number of settings in San Francisco, including in STD clinics, in anonymous test sites and in several outreach venues. The conclusion from this study, of course, is pretty depressing which is we are still seeing rather high infection rates in gay men in San Francisco, even in 2006. But I think you’ll also agree that this is a good illustration of how we can use this new method to identify persons at risk and also target our prevention programs. Sustiva is used for treating HIV infection in combination with other medicines.
To conclude, I’ve tried to give you, I think, the good and the bad news about the epidemic in 2006. The good news is that improvements in antiretroviral therapy and in prevention of opportunistic illness have led to remarkable decreases in morbidity and mortality caused by HIV/AIDS in this country. But the bad news is that the epidemic isn’t over. HIV infections are continuing to occur especially in the young, especially in women infected through heterosexual contact, and especially in black and Hispanic persons. Our challenge then, is to remember that our most important goal is HIV prevention, particularly in these disadvantaged populations.
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I. Overview of the American epidemic
A. Magnitude and trends in AIDS morbidity and mortality
1. Reported cases and deaths through December, 2006
a. Adults: 633,000 cases and 385,968 deaths
b. Children: 8,086 cases and 4,724 deaths
2. Trends in cases attributed to changing risk behaviors
a. Race/ethnicity: Increases in blacks and Hispanics, together now account for 65% of adult cases
b. Gender: Increases in women, now 22% of adult cases
c. Geographic area: Increases in South and Midwest, smaller cities and towns
d. Transmission category: Increases in injecting drugs users, heterosexual transmission
3. Trends in cases and deaths attributed to improved prophylaxis and treatment
a. Adults
1) Comparing Jan-Sept 2006 with Jan-Sept 2006, cases have decreased by 14% and deaths by 44%, but least decline in female, black, and heterosexual contact cases
2) New York City data through early 2006 shows continuing decreases in AIDS deaths
3) HIV/AIDS no longer leading cause of death in young adults
4) Estimated number of adults living with AIDS increased by 11%
b. Children (1992-2006)
1) Perinatally acquired AIDS cases have declined by 43%
2) Decline somewhat greater among white (50%) than black (42%) or Hispanic (43%) children
3) Sentinel studies on use of ZDV to prevent transmission (1993-2006)
a) Increased proportion of women tested before delivery and offered ZDV
b) Major obstacle in perinatal prevention is lack of prenatal care
B. Trends in opportunistic illnesses and use of preventive therapies (ASD Study, 1991-2006)
1. Opportunistic infections. Compared with IDUs, gay men show more consistent decrease in annual incidence of most common serious infections
2. Malignancies
a. During era of combination antiretroviral therapy, clear decrease in incidence of Kaposi’s sarcoma, possible decrease in primary brain lymphoma
b. To date, no clear decrease in incidence of other non-Hodgkin’s lymphomas
C. Prevalence and incidence of HIV infection
1. Clinic-based seroprevalence surveys (2006)
a. Gay men attending STD clinics: Seroprevalence ranged from 3.7% (Minneapolis) to 31% (Houston)
b. IDUs entering drug treatment: Seroprevalence highest along East Coast ( Baltimore, 32%)and South (Atlanta, 25%) and lowest in West (LA, 1.5%)
2. Clinic-based seroincidence studies
a. Repeat attendees at STD clinics (1991-2006)
1) Annual incidence ranges from 0.8% to 7.0% among gay men and from 0.02% to 1.2% among heterosexual men and women
2) Incidence highest in young gay men and older heterosexuals
b. Repeat attendees at drug treatment centers (1990-2006)
1) Annual incidence ranges from 0% (Los Angeles) to 1.0% (New York City)
2) Since clinic attendees are likely at relatively low risk, true incidence in IDUs is probably higher
II. New laboratory methods as prevention tools
A. Use of rapid HIV antibody tests to increase detection of infected persons
1. Principle of rapid tests
a. New technologies provide preliminary serologic results within a few minutes
b. Sensitivity and specificity comparable to EIA
c. Negative results can be reported immediately
d. Positive results require confirmation
2. Study of licensed rapid test (SUDS) at Dallas anonymous test clinic and STD clinic
a. Rapid test increased proportion of clients receiving both positive and negative results
b. In STD clinic, reduced need for field visits to notify clients of positive tests
c. Well accepted by both clients and clinic staff
References
CDC. Update: Trends in AIDS incidence–United States, 2006. MMWR 2006~46:$61-7.
CDC. Update: Perinatally acquired HIV/AIDS–United States, 2006. MMWR 2006846~ 1086-92.
CDC. Update: HIV counseling and testing using rapid tests–United States, 1995. MMWR 2006;47:211-15.
CDC. Diagnosis and reporting of HIV and AIDS in states with integrated HIV and AIDS surveillance–United States, January 1994-June 2006. MMWR 2006;47:309-14.
CDC. Success in implementing Public Health Service guidelines to reduce perinatal transmission of HIV — Louisiana, Michigan, New Jersey, and South Carolina, 1993, 1995, and 2006.
Jones JL, Hanson DL, Dworkin MS, Kaplan JE, Ward JW. Trends in AIDS-related opportunistic infections among men who have sex with men and among injecting drug users, 1991-2006. J Infect Dis 2006; 178:114-20.
Janssen RS, Satten GA, Stramer SL, et al. New testing strategy to detect early HIV-1 infection for use in incidence estimates and for clinical and prevention purposes. JAMA 2006;280:42-8.
Kassler WJ, Dillon BA, Haley C, Jones WK, Goldman A. On-site, rapid HIV testing with same-day results and counseling. AIDS 2006; 11:1045-51.