What was the design of the iPrEx study?

What was the design of the iPrEx study?

The iPrEx study was a randomized, double-blind, placebo-controlled Phase III clinical trial. Participants were randomly assigned to receive on a daily basis an antiretroviral tablet containing combination emtricitabine (FTC 200 milligrams) and tenofovir (TDF 300 milligrams)—a combination known by the brand name Truvada—or a placebo pill. The study was designed to determine whether the daily combination antiretroviral pill could safely and effectively prevent HIV infection among sexually active men who have sex with men and transgendered women who have sex with men, all of whom were routinely counseled about safe sex practices, provided condoms and treated other sexually transmitted infections. Once enrolled, all study participants were evaluated for HIV infection monthly for the duration of their participation in the study (average enrollment was 1.2 years)

What were the results of the iPrEx study?

Investigators found that study participants who took the daily dose of oral antiretrovirals experienced an average of 43.8 percent fewer HIV infections than those who received a placebo pill (95% CI 15.4 to 62.6%; P=0.005). In all, 100 cases of HIV infection occurred among participants in the iPrEx study. Of those, 36 HIV infections occurred among the 1,251 participants who were randomized to receive the study drug compared with 64 HIV infections among the 1,248 participants who were randomized to receive the placebo. The average reduction in HIV infection risk of 43.8 percent includes all study participants—even those who did not take the daily pill consistently. However, the drug’s ability to reduce the risk of HIV acquisition was greater among those volunteers who were more adherent to the daily drug regimen. Participants who took the drug on 50 percent or more days as measured by pill count, bottle count and self reporting experienced 50.2 percent fewer HIV infections (95% CI 17.9-69.7%; P=0.006). Those who took the drug on 90 percent or more days had 72.8 percent fewer HIV infections (95% CI 40.7-87.5%; P=0.001).

Overall, efficacy was greatest, 58 percent, among participants at particularly high risk for HIV, as measured by self-reports of unprotected receptive anal intercourse (URAI) at the time of enrollment in the study (95% CI 32-74%; P=add value).

The researchers found that consistent with earlier, smaller studies that led up to the iPrEx study, the antiretroviral drug proved to be safe and well-tolerated as a prophylaxis method. Side effects were mild and infrequent and included a small number of reports of transient nausea that dissipated after several weeks. Additionally, some participants who received the active drug experienced mild elevations of creatinine, a naturally occurring molecule filtered by the kidneys, but these elevations resolved spontaneously or with discontinuation of the pill.

Additionally, no HIV drug resistance occurred among individuals who became HIV-infected during the course of the study. There were three cases of emtricitabine resistance (one participant in the placebo group; two participants in the active drug group), but these cases occurred among individuals who were HIV-infected at the time of enrollment. Their HIV infections were so recent that they were not detected by standard HIV antibody testing.

Although there was concern at the launch of the study that the PrEP approach could cause study participants to relax their use of condoms and safe sex practices, this was not the case during the iPrEx study. Rather, participants reported a decrease in the number of sexual partners and increased use of condoms.

Why was the iPrEx study conducted in men who have sex with men and transgendered women
who have sex with men?

Men who have sex with men are among the groups disproportionately affected by HIV/AIDS. An article published on HIV and men who have sex with men in the December 2007 PLoS Medicine reported that men who have sex with men have a markedly greater risk of being infected with HIV than the general population in low and middle-income countries in the Americas, Asia, and Africa. Studies indicate that HIV prevalence among men who have sex with men is 10 percent or higher in each of the countries in which the iPrEx study was conducted. In the United States, 53 percent of new HIV infections occur in this population, according to 2006 HIV incidence estimates from the Centers for Disease Control and Prevention.

How was participant safety monitored during the trial?

Study participants were extensively counseled prior to enrolling in iPrEx about the purpose and design of the study, were encouraged to ask questions, and were required to pass a comprehension test to demonstrate that they understood the study and their rights as potential study volunteers to give their informed consent. Participants were free to leave the study at any time and for any reason without repercussions.

All study participants received intensive HIV risk-reduction counseling throughout the study, including free condoms and treatment for other sexually transmitted infections. HIV testing was provided on a monthly basis.

Participant safety was closely monitored throughout the trial by a data and safety monitoring board (DSMB), an independent committee composed of clinical research experts, statisticians and other representatives of the international academic research community, including representatives from the United States, Peru, South Africa, Brazil and Thailand.

Why was FTC/TDF (Truvada) selected as the study drug?

FTC/TDF was chosen for use in the iPrEx study because it has been shown to be safe and effective with few side effects as an HIV treatment for HIV-infected individuals. The drug, which is approved by the Food and Drug Administration (FDA) as an HIV treatment for HIV-infected individuals, is taken orally once daily and remains in the bloodstream for many hours. Currently, 1.5 million people worldwide are using tenofovir-based drug regimens, including FTC/TDF.

Truvada also has prevented infection when tested in nonhuman primate models of HIV infection, and it was thought that a two-drug antiretroviral combination would be more effective than a pill containing only one antiretroviral.

Truvada is not approved by the FDA for PrEP.

What is the iPrEx study?

The Chemoprophylaxis for HIV Prevention in Men study, also known as iPrEx, is a Phase III clinical study designed to determine whether a daily tablet containing a combination of two antiretroviral drugs used for HIV treatment can safely and effectively prevent HIV infection among men who have sex with men and transgendered women who have sex with men. The iPrEx study, which began in July 2007, is the National Institute of Allergy and Infectious Diseases’ (NIAID’s) first large-scale study to evaluate the investigational HIV prevention research approach known as pre-exposure prophylaxis, or PrEP.

What is pre-exposure prophylaxis?

Pre-exposure prophylaxis, or PrEP, is an investigational approach to HIV prevention in which antiretroviral medicines currently approved to treat HIV infection are given to people who are not infected with HIV in an attempt to reduce their risk of infection. The concept behind PrEP is not a new one. Drugs are taken to prevent malaria during periods of increased risk and can also be used to reduce the risk of developing tuberculosis and certain types of meningitis.

With HIV, scientists theorize that taking an antiretroviral drug before exposure to HIV could potentially inhibit HIV replication immediately after exposure to the virus, thereby preventing the establishment of permanent infection. There is scientific evidence to support this theory in animal models and humans. Antiretroviral drugs have been successfully used to prevent HIV transmission from infected mothers to their newborns.

How many participants were involved in the iPrEx study, and where was the study conducted?

The iPrEx study enrolled 2,499 sexually active men who have sex with men and transgendered women who have sex with men. All participants were at least 18 years old and HIV-negative at the time of enrollment. All participants were born male (1.2% of participants reported their current gender identity as female).

The study was conducted at 11 sites in nine cities in Brazil, Ecuador, Peru, South Africa, Thailand and the United States.

. Who funded, sponsored and conducted iPrEx?

NIAID sponsored the iPrEx study through a grant to the J. David Gladstone Institutes, a non-profit independent research organization affiliated with the University of California at San Francisco. Additional study funding was provided by the Bill and Melinda Gates Foundation. Gilead Sciences, based in Foster City, Calif., donated the study drug.

The study was conducted under the leadership of protocol chair Robert M। Grant, M.D., M.P.H., of the Gladstone Institute of Virology and Immunology, and protocol co-chair Javier R. Lama, M.D., M.P.H., of Investigaciones Medicas en Salud, a Peruvian-based research organization.

articipants in the iPrEx study are being informed

articipants in the iPrEx study are being informed of the results and counseled on the need to continue safe sex practices. Individuals who acquired HIV infection during the study were referred to appropriate medical care. Investigators will conduct a follow-on study in which all HIV-negative iPrEx participants will be offered the combination drug for 18 months. That study, which will begin in 2011, is designed to provide additional information about the drug’s long-term effectiveness and safety as well as participant risk behavior and pill-taking practices.

The NIAID-sponsored VOICE study, which launched in Sept. 2009, is examining three different, once-daily HIV prevention strategies in women: a combination pill, a pill containing only tenofovir, and a tenofovir-based vaginal gel. The study is expected to enroll as many as 5,000 women in three African countries, and results are expected in 2013.

For additional information about the iPrEx study, see the Questions and Answers and and visit the iPrEx News Web site. Visit the NIAID HIV/AIDS portal for more information about NIAID’s HIV/AIDS research.

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

The National Institutes of Health (NIH)—The Nation's Medical Research Agency—includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases.

in the final analysis, 100 cases of HIV infection

in the final analysis, 100 cases of HIV infection occurred among participants in the iPrEx study. Of those, 36 HIV infections occurred among the 1,251 participants who received the antiretroviral therapy compared with 64 HIV infections among the 1,248 participants who received the placebo. This level of effectiveness in reducing the risk of HIV infection, 43.8 percent, is statistically significant. Furthermore, the drug’s ability to reduce the risk of HIV acquisition was greater among those volunteers who were more adherent to the daily drug regimen. Participants who took the drug on 50 percent or more days as measured by pill count, bottle count and self reporting experienced 50.2 percent fewer HIV infections. Those who took the drug on 90 percent or more days had 72.8 percent fewer HIV infections.

The researchers concluded that consistent with earlier, smaller studies leading up to this trial, Truvada appeared to be safe and well-tolerated for its use in the iPrEx study. Side effects were mild and infrequent and included a small number of participants with transient nausea and mild elevations in creatinine, a naturally occurring molecule filtered by the kidneys. These elevations resolved spontaneously or with discontinuation of the drug. Additionally, very little drug resistance occurred with no instances of tenofovir resistance and three cases of emtricitabine resistance (one participant in the placebo group; two participants in the active drug group). The two cases of emtricitabine in the active drug group occurred among individuals who were in the stages of acute HIV infection at the time of enrollment, but who tested negative for HIV. Both groups of study participants reported a decrease in the number of sexual partners and increased condom use.

“The iPrEx study provides important evidence that PrEP works to reduce HIV infection risk among gay and bisexual men,” says Dr. Grant. “The need for new HIV prevention methods is critical. PrEP, in combination with other prevention methods, such as HIV testing, counseling and consistent condom use, could represent a major step forward for efforts to control the global epidemic.”

Correct and consistent condom use and a reduced number of sexual partners remain the most effective ways for gay and bisexual men to protect against HIV infection.

“A variety of expert and community advisory groups at the federal, state and local levels are looking closely at the study data and will move forward in a deliberative and measured way over the coming months to determine whether and how these findings should be incorporated into ongoing HIV prevention programs,” says Howard K. Koh, M.D., assistant secretary for health at the U.S. Department of Health and Human Services.

# Antibody discoveries propel HIV vaccine research

• Antibody discoveries propel HIV vaccine research: In the past year, researchers have discovered at least eight antibodies that can stop a wide range of HIV strains from infecting human cells in the laboratory. For instance, a team led by NIAID scientists discovered two human antibodies that can block more than 90 percent of known global HIV strains from infecting human cells, and demonstrated how one of these disease-fighting proteins accomplishes this feat. Learning the structure of the new antibodies and where they bind to the virus is helping equip scientists with the tools to design a vaccine that could stimulate healthy people to make some of the antibodies as protection against HIV infection.
  
  
• New hope for people co-infected with HIV and tuberculosis (TB): The Cambodia-based study known as CAMELIA demonstrated that the survival of untreated, HIV-infected adults with very weak immune systems and newly diagnosed TB can be prolonged by starting antiretroviral therapy two weeks after beginning TB treatment, rather than waiting eight weeks, as had been standard. This finding is valuable because beginning treatment for HIV in some highly immunocompromised individuals paradoxically can worsen the symptoms of co-infections such as TB, yet waiting too long to start antiretroviral therapy can lead to death. TB accounted for nearly a quarter of the 2 million HIV-related deaths worldwide in 2008. NIAID and the French National Agency for Research on AIDS and Viral Hepatitis co-funded the CAMELIA study.

Da ily Dose of HIV Drug Reduces Risk of HIV Infection

Daily Dose of HIV Drug Reduces Risk of HIV Infection

A daily dose of an oral antiretroviral drug, currently approved to treat HIV infection, reduced the risk of acquiring HIV infection by 43.8 percent among men who have sex with men. The findings, a major advance in HIV prevention research, come from a large international clinical trial published online Nov. 23 by the New England Journal of Medicine. The study, titled “Chemoprophylaxis for HIV Prevention in Men,” found even higher rates of effectiveness, up to 72.8 percent, among those participants who adhered most closely to the daily drug regimen.

“We now have strong evidence that pre-exposure prophylaxis with an antiretroviral drug, a strategy widely referred to as PrEP, can reduce the risk of HIV acquisition among men who have sex with men, a segment of the population disproportionately affected by HIV/AIDS,” says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. “Additional research is needed, but certainly this is an important finding that provides the basis for further investigating, developing and employing this prevention strategy, which has the potential to make a significant impact in the fight against HIV/AIDS.”

“No single HIV prevention strategy is going to be effective for everyone,” adds Dr. Fauci, “and it is important to note that the new findings pertain only to the effectiveness of PrEP among men who have sex with men and cannot at this point be extrapolated to other populations. Therefore, we must continue to conduct PrEP research among other study populations, such as women and heterosexual men, to provide a comprehensive picture of its potential utility as an HIV prevention tool.”

Landmark Discoveries Characterize NIH HIV/AIDS

NIAID MEDIA AVAILABILITY

Landmark Discoveries Characterize NIH HIV/AIDS

WHAT:
On World AIDS Day, December 1st, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, reflects on encouraging milestones from the past year in HIV/AIDS research that are advancing us toward controlling and ultimately ending the pandemic.

• Pre-exposure prophylaxis (PrEP) proves effective at reducing the risk of HIV acquisition among men who have sex with men: As published Nov. 23 in the New England Journal of Medicine online, the NIAID-sponsored study known as iPrEx found that a daily dose of an oral antiretroviral drug approved to treat HIV infection reduced the risk of HIV acquisition among men who have sex with men by 44 percent. Even higher rates of effectiveness, up to 73 percent, were found among study participants who adhered most closely to the daily drug regimen. NIAID and The Gates Foundation co-funded the iPrEx study. Additional and continued research is needed to determine whether PrEP will be similarly effective at preventing HIV infection in other at-risk populations.
  
  
• Vaginal microbicide prevents HIV infection: For the first time in nearly 15 years of research, scientists discovered a vaginal microbicide gel that gives women a level of protection against HIV infection. The CAPRISA 004 study, conducted by the Centre for the AIDS Programme of Research in South Africa (CAPRISA), found that the use of a microbicide gel containing a 1 percent concentration of the antiretroviral drug tenofovir resulted in 39 percent fewer HIV infections compared with a placebo gel. NIAID was among the organizations that provided substantial support and resources to establish the infrastructure and training for CAPRISA. Ongoing and future clinical trials will build on these study results with the goal of bringing a safe and effective microbicide to the general public.

Unprotected Sex Between HIV+ Partners: Harmful?

Unprotected Sex Between HIV+ Partners: Harmful?

(cont.)

Another concern that frequently arises during our discussions on the risks of unsafe sex between HIV-infected partners is the possibility of acquiring another strain of HIV, in particular one that might be more aggressive (virulent) or perhaps one that is resistant to antiretroviral drugs. While this possibility often is the greatest worry among the patients, we unfortunately have limited information regarding the actual risk.

I always inform my HIV patients that we are on firm ground regarding our understanding of the risks of acquiring the traditional STDs, hepatitis B, HPV, and probably hepatitis C. The data are less clear for HHV-8 and regarding the possibility of HIV super-infection (infection by another strain of HIV on top of the one the person already has). It is worth noting that there have been increasing reports of cases of suspected superinfection. Although the data remains limited it suggests that when superinfection occurs it may be associated with CD4 decline and possible disease progression. Based upon this emerging data I believe it is important for people to be aware of this potential risk while this area of research continues to evolve.

In summary, individuals need to know the currently available facts regarding the risks of unsafe sex between HIV-infected partners. If they choose to assume the known and potential risks, they should be screened for the sexually transmitted diseases and treated when possible. Finally, the clinicians and patients must maintain an open dialogue regarding evolving issues and new information as it becomes available. Although one of the greatest challenges in HIV medicine is dealing with uncertainty, honest and open discussions between patients and their healthcare providers are always the best place to start.

Viewed from another perspective, however

Viewed from another perspective, however, in a monogamous relationship between HIV-infected partners, with good diagnostic screening, the problems of gonorrhea and chlamydia are usually not insurmountable. Thus, when diagnosed, these diseases are generally curable. The same holds true for syphilis, except that it can be difficult to treat. Finally, herpes disease, although manageable, is never cured, and once acquired, results in life-long infection.

Other sexually transmitted infections can cause serious diseases that may be difficult or impossible to cure. For example, hepatitis B and C both can be transmitted sexually and may be difficult to cure. Remember, however, that hepatitis B is preventable by vaccination. While hepatitis C is more frequently spread by exposure to blood (for example, during intravenous drug abuse), transmission can occur from sexual exposure. Moreover, when hepatitis C infection occurs, about 85% of cases result in a chronic (long duration) infection that may be difficult to treat and can lead to liver failure and/or liver cancer.

The human papilloma virus (HPV) is also sexually transmitted and cannot be eliminated. It is associated with cervical cancer in women and anal cancer in both men and women. Additionally, HPV is associated with an even greater frequency of these cancers in individuals co-infected by HIV.

The human herpes virus 8 (HHV-8) has been strongly linked to Kaposi's sarcoma (a skin cancer in patients with HIV disease). Therefore, HHV-8 is clearly an infection worth avoiding if at all possible. However, it is not known just how the spread of HHV-8 occurs and how it can be prevented. It may very well be transmitted sexually. At this time, however, there is no readily available way of determining whether an individual is infected with this virus.

Unprotected Sex Between HIV-Infected Partners: What's the Harm?

Unprotected Sex Between HIV-Infected Partners: What's the Harm?

At least once a week, I am asked by one of my HIV-infected patients whether they need to continue to practice safe sex if they are in a monogamous (one mate only) relationship with an HIV-infected partner. Put another way, since both partners already have HIV, what's the harm of unprotected sex? Actually, this is not an easy question to answer fully. My belief, however, is that the best approach is to provide as much information as possible; emphasizing what is known versus what is uncertain. Such a complete disclosure is the only way I can remain credible while allowing the patient to make a fully informed decision.

My response to this question generally begins by telling the patient what is known about the risks of unsafe (unprotected) sex between HIV-infected partners. First of all, we know that in this situation, the spread of other sexually transmitted diseases (STDs), such as gonorrhea, chlamydia, syphilis, and herpes remains a risk, as usual. What's more, these so-called traditional STDs are well known to be associated with serious complications.

Both gonorrhea and chlamydia initially can cause infections of the urethra (urethritis) and anus, or rectum (proctitis). Subsequently, these infections can progress to serious complications in these areas and even spread to other parts of the body. In addition, in women, gonorrhea and chlamydia are associated with increased risks of infertility and ectopic pregnancy, which at times can be life-threatening. (An ectopic pregnancy occurs when the fertilized egg implants outside of the uterus; for example, in the tubes.)

Growing Epidemics of HIV in Eastern Europe

Growing Epidemics of HIV in Eastern Europe

A second plenary talk in the morning was by Christopher Beyrer, Associate Professor of Epidemiology and International Health at the Johns Hopkins Bloomberg School of Public Health in Baltimore Maryland. Dr. Beyrer does research around the world and spoke of the growing epidemics of HIV, particularly in Eastern Europe. In this region of the world many new infections result from intravenous drug use. He further explained that many countries have failed to deal with the unique problems of intravenous drug users. For example, in the roll out of antiretroviral therapy to poor countries distribution has often not provided for those who use drugs. In addition, many areas do not promote risk reduction in this group, such as by distribution of clean needles, a method that has been proven in several studies to reduce HIV transmission among drug users.

Patient zero - HIV-1 Strain

There were several other presentations during the day that will be of interest to the community. Dr. Blick presented a paper called "Patient zero: The Connecticut source of the multi-drug resistant dual-tropic, rapidly progressing HIV-1 strain found in New York City." He first reminded the group of a unique case that was reported by a press release earlier this year from the New York Health Department. It was a crystal methamphetamine-using individual who appeared to have been infected for months to a few years that had acquired a virus resistant to most antiretroviral agents and was experiencing rapid disease progression. The primary provider for this patient was contacted by companies that performed the resistance testing stating that they identified an individual with a virus that appeared to be highly related to that of the patient. Dr. Blick described how the person identified by the company, along with this individual's stable HIV-infected partner admitted to sexual relations with the "NY patient" around the time of his new infection. Further studies demonstrated evidence that there was some exchange of viruses between the HIV-infected stable partners and that their viruses were very similar to that of the New York patient. Despite this, the persons that were presumed to be the source or the virus had been infected for many years and did not experience rapid disease progression, as seen in the NY case. While there are still many details that need to be sorted out from these cases, there are several important lessons to be learned. First, it illustrates that crystal methamphetamine-use continues to be an important driving force behind the HIV epidemic. Second, it emphasizes the importance of using barrier protection, including among HIV-infected partners, where in this case there was evidence of possible superinfection which could have adverse effects on the course of disease. Finally it shows that rapid progression is influenced by a multitude of factors, not just the virus. Further research related to patients like this may someday advance our understanding of why different people handle viruses differently.

HIV / AIDS Conference -

HIV / AIDS Conference - Monday July 25, 2005

Welcome from the 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment in Rio de Janeiro Brazil. The International AIDS Society (IAS) is the world's professional society for scientists, health care and public health worker, and other engaged in HIV/AIDS prevention, control and care. Delegates arrived in Rio de Janeiro from across the globe to share information regarding a wide range of scientific areas. This meeting includes new information regarding novel therapeutic agents as well as prevention measures in both the developed and developing world. Recent International meetings have further focused on the roll out of antiretroviral therapy to some of the countries most devastated by the HIV/AIDS epidemic.

Diversity of HIV Strains

The first full day of the meeting began with a presentation by Dr. Francine McCutchan who leads the Global Molecular Epidemiology Programme for the U.S. Military HIV Research Program. Dr. McCutchan presented data from work showing the diversity of HIV strains around the world. In addition to outlining how such extensive viral diversity may hinder the ability to develop a protective vaccine she also showed how these viruses can further mix within a given individual. This situation has been referred to as recombination and it rapidly results in new strains that are different from those previously recognized. Many of these new viruses have subsequently spread throughout different parts of the world. More recent work has used novel laboratory techniques to explore how often a given individual is infected by more than one strain of HIV, so called co-infection. This can occur as a result of an uninfected person being simultaneously infected by two different partners around the same time, or for a chronically infected person to be re-infected by a new partner, so called superinfection. This study showed that amongst those chronically infected who have many partners there is an increasing number with evidence of superinfection, in fact it may occur in up to 40% of select individuals. These types of studies have major implications for those infected by HIV. Firstly it illustrates how variable HIV can be, which will certainly make vaccine development very challenging. In addition it supports current recommendations that those infected with HIV do everything possible to prevent themselves from becoming superinfected. In fact, other studies have suggested that when superinfection occurs it is often associated with disease progression.

A patient information sheet provided

A patient information sheet provided with the new test will outline the limitations of urine HIV-1 testing in addition to the usual information on HIV and AIDS provided to people before HIV testing. After reading the information sheet, the person being tested will initial the statement confirming the receipt of the pre-test counseling, peel off the sample label and apply it to the urine collection cup. FDA's approval was based on clinical studies demonstrating that the test is sufficiently accurate for screening in medical and public health settings. The urine-based ELISA test is not approved to screen blood donors. For that purpose, more accurate ELISA tests using blood samples are required.

In the clinical studies, urine and blood samples were taken from 298 patients diagnosed with AIDS and tested with both the Calypte HIV-1 Urine EIA and a licensed ELISA test using a blood specimen. The urine test was positive as an initial screening test 99.3% of the time in persons known to have AIDS. In asymptomatic HIV-1 infected patients, the test would be expected to miss 1 or 2 people in every 100.

Other studies showed that the urine-based test would give a falsely positive result in one or two people out of 100 without HIV-1 antibodies in their blood, compared to one in 1000 with a blood-based ELISA test.

ROCKVILLE, MARYLAND--On August 6, 1996

ROCKVILLE, MARYLAND--On August 6, 1996, the Food and Drug Administration approved the first HIV test that uses urine samples. All previously approved HIV tests use either blood or oral fluid samples.

The new urine-based test detects the presence of antibodies to HIV-1, the virus that causes the vast majority of U.S. AIDS cases, using an enzyme linked immunosorbent assay (ELISA) method.

The test is approved to screen for HIV-1 infection and may be useful for medical purposes when the collection of blood samples is impractical.

The test is manufactured by the Calypte Biomedical Corporation of Berkeley, Calif., and will be marketed as the Calypte HIV-1 Urine EIA. It will also be marketed by Seradyn Inc. of Indianapolis, Indiana as the Seradyn Sentinel HIV-1 Urine EIA.

The test can be ordered only by a physician. Samples will be analyzed in certified medical laboratories. Any initially reactive sample will be retested twice. If even one of the second tests is reactive, the screening test will be considered positive, although this positive result does not always indicate HIV infection.

For confirming a positive screening test, anyone testing positive with the Calypte test must be retested with a more accurate test using a blood sample.

Investigators have also proposed other goals for the interruption

Investigators have also proposed other goals for the interruption of treatment. For example, the suggestion has been made that patients who have developed resistance to their antiretroviral therapy may be able to stop the therapy to allow the resistant virus to "go away." Then, a new drug regimen can be started with enhanced viral suppression. Finally, others have proposed serial interruptions of therapy to minimize the amount of time people are actually taking their medications. The hope here is that the diminished time on the drugs will result in less toxicity for the patient.

So, the goals of interrupting therapy in these different situations differ. Yet, despite these important differences, each of these strategies has been described in a similar way, as "strategic, structured, or scheduled" treatment interruptions, often abbreviated as STI. The problem is that this one term, STI, has been used loosely to describe various situations. As a result, this use of the term STI has led to considerable confusion among patients and their doctors.

Consequently, it is vital that people understand certain key aspects of each of these different strategies. For instance, for each situation, people need to know the circumstances under which STI is being explored, the data supporting the use of STI, and the potential risks of STI. Below, I have outlined the situations in which interruption of treatment, or STI, is currently being considered.

In 1995, the availability of potent antiretroviral therapy changed the management of HIV

In 1995, the availability of potent antiretroviral therapy changed the management of HIV infection forever. At that time, "drug cocktails" of medications became the standard of care, with the ultimate goal being long-term viral suppression. The subsequent years brought the realization, however, that long-term antiretroviral therapy also had its limitations, such as the development of drug resistance and toxicity. Nevertheless, simultaneously, major advances were being made in the understanding of HIV immunology.

For example, studies demonstrated that during the first months of infection, the body ordinarily mounts an immune (defensive) response to the virus. This response results in variable levels of viral control. Yet, notably, in rare cases, without therapy, the immune system is able to suppress the viral load to very low levels for prolonged periods of time. These fortunate, albeit rare, individuals have been referred to as long-term nonprogressors. On the other hand, when the virus is suppressed by antiretroviral therapy, the body's natural immunity is not stimulated by the presence of virus in the blood, and thus, the immunity declines.

This important immunologic data provided a scientific rationale for considering interruption of antiretroviral therapy. The idea of interrupting treatment is to allow the viral load to increase and thereby, stimulate the body's immune response to the virus. In other words, the virus already in the body stimulates the body's immune response in a reaction referred to as "autoimmunization." (You see, "auto" means self.) With a regular immunization, in contrast, the virus, previously rendered harmless, is injected into the body to generate the immune response. Accordingly, the goal of this strategy of autoimmunization is to allow the immune system itself to control viral replication (reproduction) after therapy was interrupted.

Moreover, many of the factors associated with new HIV infections

Moreover, many of the factors associated with new HIV infections, outlined above, are associated with a reluctance to get tested and diagnosed, and to enter into treatment. Furthermore, even if those individuals who are infected enter into treatment, factors such as depression, illicit drugs, and alcohol abuse often limit their ability to strictly follow their medication regimens. This poor adherence then promotes the development of resistance by the HIV to the medications (drug resistance), which, in turn, increases the risk of progression to symptoms and death.

Finally, the issues discussed above may in part explain why there has been a leveling off or even a slight increase in AIDS-related deaths. Thus, many individuals are dealing with issues that prevent them from getting into care, or when entered into care, being successful with their treatment. In addition, people who do not perceive themselves to be at risk are less likely to get tested for HIV. Consequently, these people often first find out they have HIV when they are having symptoms from AIDS. As a matter of fact, many people I care for who have HIV disease and symptoms or who have died from AIDS during the last few years are coming to the hospital without having ever been tested for HIV.

Only a better understanding of the reasons for these trends in HIV disease will enable us to approach the underlying basic problems. Hopefully, studies that address all of these issues will ultimately lead to changes in our national HIV prevention efforts. These changes should then reduce the number of new HIV infections, cases of AIDS, and AIDS-related deaths. In the interim, education and encouraging people to get tested remain a good start

Why would these gay men put themselves at increased risk

Why would these gay men put themselves at increased risk? Actually, many factors may be contributing to this major setback in our efforts to control HIV. For one thing, there is the inappropriate perception that therapy is so good that getting infected is no longer a "big deal." For another, many individuals are putting themselves at risk because they suffer from depression, drug and alcohol abuse, or sexual addiction. While education has been the mainstay of HIV prevention, these observations illustrate that there are indeed underlying, basic problems. Moreover, these fundamental problems need to be better identified and addressed if there is to be a decrease in the overall infection rate.

With no decline in the rate of new HIV infections and an initial decline in AIDS deaths, increasing numbers of HIV-infected individuals are to be expected. Of course, this increase would expand the population that can then transmit HIV to others. At the same time, it also would increase the number of individuals that can eventually progress to AIDS and death.

Americans continue to be contracting HIV and dying from AIDS.

I am frequently asked why, despite major educational campaigns and the development of new therapies, Americans continue to be contracting HIV and dying from AIDS. In fact, in association with the availability of more effective antiretroviral therapy, a sharp decline did occur in AIDS deaths between 1995 and 1997. The current estimate is that there are approximately 15-20,000 AIDS deaths per year, down from 40-50,000. However, the estimated rate of new HIV infections in the United States has not declined and has remained stable at approximately 40,000 per year.

Let us consider the HIV problem as a continuous sequence (continuum) from the initial HIV infection, to clinical progression with symptoms and AIDS, and finally to death. This approach enables us to address each potentially significant factor individually. First of all, the nature of the HIV epidemic has changed. For example, increasing numbers of people are being infected who do not perceive themselves to be at risk, such as heterosexual women. In addition, there is evidence that even gay men, particularly younger individuals, are putting themselves at increasing risk.

Why Circumcision Protects Against HIV and AIDS?

Why Circumcision Protects Against HIV and AIDS?

The explanation for this remarkable effect seems logical. The HIV virus targets certain cells called Langerhans cells that are present in abundance on the inner surface of the foreskin. These cells are likely "the primary point of viral entry into the penis of an uncircumcised man." Langerhans cells possess HIV receptors, making them particularly susceptible to infection. Male circumcision may act to provide significant protection against HIV infection by removing most of the receptors.

Whether to Circumcise or Not?

In light of the available evidence, male circumcision should clearly be considered as a measure to prevent HIV in countries with a high level of infection. Should the matter of AIDS (and other STDs) figure into the decision whether or not to circumcise a boy here?

To Circumcise Or Not? - The Matter of AIDS

To Circumcise Or Not? - The Matter of AIDS

Berkeley, California, June 12, 2000 -- For some time, circumcision has been a matter of debate in the world at large and within our family which is large enough to contain some differing opinions and both circumcised and uncircumcised males.

The National Organization of Circumcision Information Resource Centers (NOCIRC) states that it is "dedicated to making a safer world" and "committed to securing the birthright of male and female children and babies to keep their sexual organs intact."

Not everyone equates male and female circumcision. No health rationale can be conjured up to defend female circumcision. But there are some health reasons for male circumcision.

The Protective Effect of Circumcision Against HIV

Among the foremost factors favoring male circumcision today is its protective effect against HIV (the human immunodeficiency virus), the agent of AIDS.

Uncircumcised men are known to be at much greater risk of becoming infected with HIV than circumcised men. Over 40 studies have found that men who are circumcised have a lower risk of becoming infected with HIV from an infected sexual partner than uncircumcised men. Circumcised men are two to eight times less likely to contract HIV and other sexually transmitted diseases (STDs) than uncircumcised men.

Perhaps the most dramatic evidence for this protective effect has just appeared in a new study published in the British Medical Journal (BMJ). The study was of couples in Uganda where each woman was HIV positive and her male partner was not. Over a period of 30 months, no new infections occurred among 50 circumcised men, whereas 40 of 137 (29.2%) of the uncircumcised men became infected -- even though all couples were given advice about preventing infection and free condoms were available to them

When To Call A Professional

When To Call A Professional

Call your doctor if you believe that you have been exposed to the body fluids of someone who has HIV or AIDS. If you test yourself for HIV at home, call your doctor immediately if your result is positive. Even if your result is negative, speak with your doctor about your concerns, questions, how to prevent HIV infection, and the need for follow up testing.

Prognosis

The average time for HIV infection to progress to AIDS is 10 to 11 years if the person does not use antiviral medication or if just one antiviral drug (monotherapy) is used. However, in about 20% of people with HIV infection, usually those with the highest viral load, AIDS develops sooner (5 years after infection). In 2% of people, it develops later (more than 12 years after infection).

Once HIV infection has progressed to AIDS, there is an increased risk of death that varies dramatically from person to person. For example, some people with AIDS have died shortly after they were diagnosed, whereas others have lived 12 years or more. Since the FDA approved newer antiretroviral drugs in 1995, the number of deaths from AIDS has decreased dramatically in the United States. The rate of AIDS hospitalizations and complications also declined.

Treatment Your doctor may choose a combination of drugs to fight HIV infectionaa

Treatment

Your doctor may choose a combination of drugs to fight HIV infection. These drugs are called antiretroviral therapy. By using several drugs simultaneously (often called a drug cocktail), your doctor hopes to increase the effectiveness of AIDS treatment by attacking HIV at multiple points. Combining drugs also limits the risk that HIV will become resistant to drugs, which would make the drugs ineffective.

Many studies have shown that people with high levels of virus in the blood (the viral load) will progress more rapidly to AIDS. Though it is not possible to completely clear the virus from the body, the goal of anti-retroviral therapy is to suppress the virus so that it cannot be detected in the blood, to increase the CD4 count, and to strengthen the weakened immune system. Currently available anti-retroviral drugs include:

• Nucleoside reverse transcriptase inhibitors, such as zidovudine (Retrovir, AZT), didanosine (Videx, ddI), stavudine (Zerit, d4T), abacavir (ABC) and lamivudine (Epivir, 3TC). There is a combination pill called Combivir, which contains lamivudine and zidovudine. Tenofovir (Viread) is a commonly prescribed drug in a related family (nucleotide reverse transcriptase inhibitors).
• Protease inhibitors, such as saquinavir (Invirase, Fortovase), ritonavir (Norvir), indinavir (Crixivan), nelfinavir (Viracept); these also come in combinations, such as lopinavir/ritonavir (Kaletra)
• Non-nucleoside reverse transcriptase inhibitors, such as nevirapine (Viramune), and efavirenz (Sustiva)
• Fusion inhibitors, such as T-20 (Fuzeon)

One common treatment approach is HAART (highly active antiretroviral therapy), which combines three nucleoside analogues, two nucleoside analogues and one protease inhibitor, or two nucleoside analogues and one non-nucleoside reverse transcriptase inhibitor. Many other variations exist. Many of these drugs have side effects, such as nausea and diarrhea. In addition, some have severe drug interactions with commonly used medications. Fusion inhibitors are reserved for patients who are infected with a drug-resistant HIV strain.

The U.S. Food and Drug Administration (FDA) has approved more than 22 drugs for treating AIDS-related conditions, including drugs that fight opportunistic infections and Kaposi's sarcoma. In addition to these medications, people with low CD4 counts should take certain medications to prevent the development of opportunistic infections. For example, people should take trimethoprim-sulfamethoxazole (Bactrim) if their CD4 count is less than 200 per cubic milliliter of blood.

Treatment scams for AIDS rob trusting people of up to $10 billion annually. To fight these scams, the FDA formed the AIDS Health Fraud Task Force in 1989. Based on results of FDA investigations, some unapproved therapies to avoid are "energized" water, "ozone therapy" and the hydrogen-peroxide "treatment."

HIV infection can be passed from person to person in any of the following ways:

Prevention

HIV infection can be passed from person to person in any of the following ways:

• Unprotected sexual intercourse (heterosexual or homosexual)
• Oral sex with an infected person
• A contaminated blood transfusion (very rare in the United States since 1985, when blood supplies started being tested for HIV)
• Needle sharing (if one intravenous drug user is infected)
• Occupational exposure (needle stick with infected blood)
• Artificial insemination with infected semen
• Organ transplant taken from an HIV-infected donor

Newborns can catch HIV infection from their mothers before birth or through breastfeeding.

There is no evidence that HIV can be spread through the following: kissing; sharing food utensils, towels or bedding; swimming in pools; using toilet seats; using telephones; or having mosquito or other insect bites.

Although several HIV vaccines are being tested, none has been approved. You can decrease your chances of being infected with HIV by avoiding high-risk behaviors. To decrease the risk of HIV infection:

• Don't have sex, have sex with only one partner who is also committed to having sex with only you or use barrier methods of contraception such as condoms.
• If you use intravenous drugs, never share needles.
• If you are a health care worker, strictly follow universal precautions (the established infection-control procedures to avoid contact with bodily fluids).
• If you are a woman thinking about becoming pregnant, have a test for HIV beforehand, especially if you have a history of behaviors that put you at risk of HIV infection. Pregnant women who are HIV-positive need special prenatal care and medications to decrease the risk that HIV will pass to their newborn babies.

Diagnosis Your doctor will ask about possible HIV risk factors,

Diagnosis

Your doctor will ask about possible HIV risk factors, such as previous sexual partners, intravenous drug use, blood transfusion and occupational exposure to blood. Your doctor will ask about a variety of symptoms, such as fever, weight loss, muscle and joint aches, fatigue and headache, and about medical problems you may have had, such as skin rashes or infections, sinusitis, pneumonia and yeast infections. This typically is followed by a complete physical examination. Your doctor will look for a thick, white coating on your tongue that may be thrush (infection with Candida fungus), skin abnormalities such as Kaposi's sarcoma or recurrent infections and other abnormalities that suggest the diagnosis of AIDS.

HIV testing can be done in your doctor's office or in an anonymous clinic. Your doctor will confirm the diagnosis of HIV infection through blood tests. The initial screening test is called enzyme linked immunosorbent assay (ELISA). It detects disease-fighting proteins in your immune system (antibodies) specific to HIV. A Western blot test, which also measures the body's response to HIV, is more accurate, and is done to confirm the diagnosis. Neither the ELISA nor Western blot is accurate immediately after exposure to the HIV virus. It can take a few months for these tests to become positive.

The period between infection with HIV and the development of positive test results on ELISA and Western blot is called the window period. This term refers to the window of time between getting the HIV infection and the ability to detect the body's response to infection with one of these two tests. If the test results are positive, another test, called the HIV RNA blood test, can measure the amount of HIV virus in the blood (viral load). To confirm the diagnosis of AIDS, your doctor will order a blood test for CD4 cell count. A count less than 200 cells per cubic milliliter of blood indicates AIDS. You also may have tests to diagnose AIDS-related conditions, including opportunistic infections, brain illness, a tumor, body wasting or lung illness, depending on your symptoms.

Symptoms

Symptoms

In its early stages, HIV infection has no symptoms or causes only a flu-like illness with many of the following symptoms: fever, sore throat, rash, nausea and vomiting, diarrhea, fatigue, swollen lymph nodes, muscle aches, headaches and joint pain. Although 50% to 90% of people experience symptoms within the first few weeks of contracting HIV infection, most people and doctors dismiss the illness as a routine cold or flu. In a small number of cases, this early stage of infection may progress to meningitis (inflammation of membranes covering the brain) or other severe flulike symptoms that require hospitalization.

As the number of CD4 cells drops below normal (800 to 1,200 cells per cubic millimeter of blood), the person may begin to develop swollen lymph nodes and skin problems, such as seborrheic dermatitis (dandruff), new or worsening psoriasis and minor infections. Ulcers can develop around the mouth.

Over the next few years, as CD4 cells continue to die, skin problems and mouth ulcers develop more often. Recurring herpes and varicella-zoster infections (shingles) can occur. Many people develop diarrhea, fever, unexplained weight loss, joint and muscle pain, and fatigue. Old tuberculosis infections may reactivate even before AIDS develops. (Tuberculosis is one of the most common AIDS-related infections in the developing world.)

Finally, with further decreases in the levels of CD4 cells, the person develops AIDS. In an HIV-infected person, some signs that AIDS has developed are:

• The CD4 count has decreased to 200 cells per cubic milliliter of blood or fewer.
• An infection has developed, causing certain types of pneumonia, diarrhea, eye infections or meningitis. Some of the germs that can cause these opportunistic infections include Candida fungus, cryptococcosis, cytomegalovirus, herpes simplex virus, Mycobacterium avium complex and Pneumocystis carinii. The person also can develop fungal infections specific to certain areas of the United States, such as histoplasmosis and coccidioidomycosis.
• A tumor has developed, including cervical cancer, Kaposi's sarcoma (cancer-causing round, reddish spots in the skin and mouth), certain types of non-Hodgkin's lymphoma or brain lymphoma.
• An AIDS-related brain illness has developed, including HIV encephalopathy (AIDS dementia) or progressive multifocal leukoencephalopathy.
• There is severe body wasting (HIV wasting syndrome).
• There is an AIDS-related lung illness, such as pulmonary lymphoid hyperplasia or lymphoid interstitial pneumonia (usually seen only in children).

What Is It?

What Is It?

The human immunodeficiency virus (HIV) weakens the body's immune defenses by destroying CD4 (T-cell) lymphocytes, which are a group of white blood cells that normally help guard the body against attacks by bacteria, viruses and other germs. When HIV destroys CD4 lymphocytes, the body becomes vulnerable to many different types of infections. These infections are called opportunistic because they have an opportunity to invade the body when the immune defenses are weak. HIV infection also increases the risk of certain cancers, illnesses of the brain (neurological) and nerves, body wasting and death. The entire spectrum of symptoms and illnesses that can happen when HIV infection significantly depletes the body's immune defenses is called acquired immunodeficiency syndrome or AIDS.

Since 1981, when HIV/AIDS was first recognized as a new illness, scientists have learned much about how a person becomes infected with HIV. The virus is spread through contact with an infected person's body fluids, especially through blood, semen and vaginal fluids. Once inside the body, HIV particles invade CD4 lymphocytes and use the cells' own genetic material to produce billions of new HIV particles. These new particles cause the infected CD4 cell to burst (lyse). The new particles can then enter the bloodstream and infect other cells. Once someone is infected with HIV, their number of normal CD4 cells continues to decrease.

Eventually, the number of normal CD4 cells drops below the threshold level needed to defend the body against infections, and the person develops AIDS. Doctors used to think that HIV was inactive (dormant or latent) between the initial infection and the diagnosis of AIDS. We now know that HIV is active, copying itself and killing CD4 cells from the time the infection starts through and beyond the diagnosis of AIDS.

Within the past two decades, about 60 million people worldwide have become infected with HIV. More than 20 million have died. More than 90% of these people live in developing countries. In some parts of Africa, more than half of adult deaths are caused by HIV infection, leaving millions of children orphaned after their parents died of AIDS. In the United States, as of the end of 2002, there were more than 886,000 cases of AIDS reported, with almost 500,000 deaths, including 5,315 children. HIV rates are increasing most rapidly among minority populations. The infection occurs 6 times as often in African-Americans and 3 times as often in Hispanics compared with whites.

Maturation

Maturation

HIV matures and the cycle starts again.

During (or soon after) the budding of the new HIV particle from the host cell membrane, the viral proteinase in p160 becomes active, generating the mature form of HIV. It's at this final step the the cycle begins again to form more HIV.

Extrusion

Extrusion

The new virus gets its lipid coating.

As the virus buds from the cell, it acquires a lipid coat, carrying the gp 120 and gp 41 proteins. The virus is extruded into extra-cellular space in this immature state.

Assembly

Assembly

Viral assembly

Proteins associate with the inner surface of the plasma membrane and interact with proteins present in the plasma membrane. As these proteins accumulate on the inner surface of the plasma membrane, they aggregate and commence assembly to form the virus. As assembly continues, the new HIV leaves the cell.

Translation

Translation

The viral RNA leaves the cell.

The viral mRNA leaves the nucleus. The translation of the viral mRNA results in the synthesis of three polyproteins essential in the continue process of viral reproduction.

Transcription

Transcription

Changing DNA to RNA.

Once inside the host cell nucleus, the RNA changes viral DNA into RNA.

Integration

Integration

Integration of DNA into the host cell.

The viral DNA migrates to and enters the host cell nucleus and becomes integrated into the cell DNA with the help of the enzyme integrase.

Reverse Transcriptase

Reverse Transcriptase

Synthesis od double stranded DNA

Reverse transcriptase synthesizes a double-stranded DNA copy of the single-stranded viral RNA generating a provirus.

Uncoating

Uncoating

Uncoating of the viral RNA

Partial uncoating of the viral core occurs to expose the viral RNA. Once in the cell cytoplasm, the conversion of the viral RNA into double-stranded DNA commences as the viral reverse transcriptase becomes active.

Penetration

Penetration

Penetration of the genetic material

After attachement, HIV releases genetic material into the CD4 cell.

HIV Binding

HIV Binding

HIV binding to the CD4 target cell

The HIV infection starts with the attachment of HIV by way of the gp120 protein to the CD4 target cell.

Reverse Transcription

Reverse Transcription

Once in the cell, the single stranded RNA of the HIV must be converted to the double stranded DNA. It accomplishes this with the help of the enzyme reverse transcriptase. Reverse transcriptase uses building blocks from the T-cell to help change the HIV RNA to DNA. The DNA contains the genetic information needed for HIV reproduction.

Drugs called reverse transcriptase inhibitors block HIV's reverse transcriptase from using these building blocks. Nucleoside and nucleotide analog reverse transcriptase inhibitors (NRTIs) and contain faulty imitations of the proteins found in a T-cell's cytoplasm. Instead of incorporating a protein into the growing chain of DNA, the imitation building blocks in NRTIs are inserted, which prevents the double strand of DNA from becoming fully formed.Non-nucleoside reverse transcriptase inhibitors block reverse transcription by attaching to the enzyme in a way that prevents it from functioning.

NNRTI Fact Sheets

Integration

To use the cell to reproduce, it must integrate the newly formed DNA into the cell nucleus. While the process is not fully understood, it is thought to be aided by transport proteins supplied by HIV.

Viral Latency

Once integration has occurred, HIV must wait for more protein building blocks to be formed by the cells or in other words, HIV is waiting for materials it needs to complete the reproductive process.

Final Assembly

Now that all the materials are available, they must be separated (cleavage) and assembled into new HIV. This process is possible because of the enzyme protease. This enzyme separates the parts allowing them to be reassembled into new HIV.

Drugs called such as Kaletra, Crixivan, and Viracept bind to the protease enzyme and prevent it from separating, or cleaving, the subunits.

Budding

The final step of the viral life cycle is called budding. With its genetic material tucked away and a new outer coat made from the host CD4 cell's membrane, the newly formed HIV pinches off and enters into circulation, ready to start the whole process again. This is obviously a very simple look at the HIV life cycle. But it gives you an idea of what an intricate process HIV replication is. Our understanding of the life cycle continues to grow and from that knowledge new drugs targetting new stages in the life cycle are being developed. Giving HIV+ people medication options makes understanding the HIV life cycle a must.

Introduction of HIV

Understanding the HIV life cycle and HIV replication has made it possible to develop the medications we use to treat HIV and AIDS. Knowing about HIV replication or how HIV makes copies of itself allows us to develop ways to block the process, and in turn slow HIV's attack on our immune system. This article will explain the process of HIV replication, will review the HIV life cycle step-by-step and will explain what HIV medications do to interrupt the process.

Introduction of HIV

Obviously, before HIV infection can occur it must enter the body. Exposure to infected bodily fluids through sexual contact or sharing of neeedles is the primary way HIV enters the body. Infection through child birth and breastfeeding are also ways people become exposed to HIV.

HIV Infection Routes and Risks

Viral Attachment

Once in the body, HIV needs a host to help it reproduce. The host in the case of HIV is the T-cell or CD4 cell. HIV seeks out CD4 cells and must attach to them by way of a "lock and key" type system. Proteins on the surface of HIV attach to complimentary proteins on the CD4 cell much like the way a key fits into a lock.

This is What Viral Attachment Looks Like

Viral attachment is blocked by the class of drugs called entry inhibitors. Blocking this stage prevents HIV from using the T-cell. If allowed to attach, HIV uses the cell for the next steps in reproduction.

Question: Symptoms of HIV - What Does HIV Do to Your Body?

Question: Symptoms of HIV - What Does HIV Do to Your Body?

What are the symptoms of HIV? How does HIV change your body? The symptoms of HIV after being infected; AIDS defining illnesses occur if you don't get treatment. What do the symptoms of HIV do to your body? This page will provide the answer to your frequently asked question about the symptoms of HIV.

Answer:
HIV is a virus that uses the genetic material from our CD4 cells to make more copies of itself. The virus likes one particular cell in our immune system called a CD4 cell or t-cell. When it uses that cell's genetic material, it damages the T-cell making it unable to do its job in our immune system. The more of these CD4 cells that are damaged, the weaker your immune system becomes. Eventually, your immune system will become so weak that it will not be able to protect you from other illnesses and infections, thus you become sick. Simply put, HIV doesn't make you sick. It weakens your immune system, allowing other illnesses and infections to make you sick.

HIV for a Lifetime

HIV for a Lifetime

In the fight against HIV new drugs, called protease inhibitors and non-nucleoside reverse transcriptase inhibitors, have brought hope to many infected persons. When combined with older drugs like AZT, these 'drug cocktails' are very effective in suppressing the amount of HIV virus in the body. However, new research suggests that even when suppressed to almost undetectable levels, the HIV virus remains in the body for a long time, perhaps even for life.

Scientists at the Johns Hopkins Moore HIV Clinic recently announced a study in which they followed approximately 35 patients with HIV for two years. The patients were all taking some form of a drug cocktail and had very low levels of detectable HIV in their blood.

The researchers found that the HIV virus is resilient. Even with undetectable amounts in the blood, the virus remains in the patients' bodies. The virus "hides" in a type of T cell in the immune system. When these T cells are inactive, the virus integrates itself into the cell's DNA making it extremely difficult to detect.

When the patient experiences an immune response, from a simple cold for instance, these T cells are activated. In the process, the HIV is activated as well, taking over the cellular production machinery and replicating itself millions of times.

The study illustrates that it is extremely important that people with HIV continue taking the HIV cocktail--perhaps for a lifetime. The drugs would counteract the produced virus. Without the cocktail, the patients would succumb to the deadly affects of AIDS.

Using sensitive cellular sorting techniques and a statistical projection model, scientists determined that the HIV virus could lay dormant for 60 years, perhaps more. In addition, the sorting techniques revealed that when the cocktail therapy is maintained, the level of dormant cells containing the HIV virus remains relatively stable.

Patients on the regimen have to be vigilant in taking their medicine. Some forms of the cocktail therapy require patients to take the medicines at strict times during the day and to make significant modifications to their diet.

Researchers admit that the long dormancy of the virus will make finding a cure for HIV that much more difficult.

What do you think? From an evolutionary standpoint, how did the virus develop this "hiding" mechanism? Will we ever find a cure, or will we simply "manage" the disease? Come over to the Biology Forum and share your thoughts, opinions, and feelings. 'Til next time...

How Does the HIV Virus Multiply?

How Does the HIV Virus Multiply?

Once inside the body the virus attacks specialized immune system cells known as CD4 cells. The HIV virus attaches to these cells and infects them by injecting HIV proteins (DNA and RNA) into the cell. The new HIV virus then infects other CD4 cells as the cycle repeats itself.

How Does the HIV Virus Harm the Body?

As the HIV virus reproduces, the CD4 cells are damaged, becoming unable to fight infections. As this process continues, the body's immune system weakens and the infected person becomes susceptible to a score of different infections, all capable of making the person sick and in extreme cases can lead to death.

What Can Be Done to Stop the HIV Virus?

While there is no cure for HIV, medications are now available that diminish the virus's ability to reproduce. This in turn helps the immune system stay healthy and able to fight infection. Keep in mind that these medications can't rid the body entirely of HIV and people can still infect others while on medications.

One Virus Fighting Another

One Virus Fighting AnotherOne Virus Fighting Another
Scientists from the VA Healthcare System and the University of Iowa School of Medicine are studying how one harmless virus impacts the progression from HIV to AIDS. In a study looking at blood samples from 1984 to 1990, researchers found that those patients infected with the harmless virus GBV-C progressed to AIDS much slower than those only infected with HIV. GBV-C is a relatively common virus that is harmless to humans, causing no symptoms or illness. The blood samples used in the study were from 271 men who were HIV negative at the onset of the study but who were positive by time the study follow-up was done. The study showed that those HIV-infected men with persistent GBV-C infection along with HIV progressed to AIDS three times slower than those men infected with only HIV. Those men with GBV-C had much slower immune system destruction compared to those without GBV-C. While there is no immediate use for this discovery, researchers are now studying samples from women to see if the same trends hold true.

Gene Therapy

Gene Therapy

Researchers at the University of Pennsylvania School of Medicine have reported favorable results using gene-based therapies in the fight against HIV. Gene therapy uses genetically altered CD4 cells that are resistant to HIV, protecting them from the damage caused by the virus. By protecting the CD4 cells, the immune system is preserved and remains able to do its job of fighting infection. In Phase I of the gene therapy trials, the experimental drug VRX496 was given to five patients who previously demonstrated resistance to conventional HIV therapies. When they re-examined the five after nine months of therapy, four of the five showed stable or increased CD4 counts, as well as improved immune system function. In addition, a decrease in HIV viral load was observed in three of the patients. While these results are positive, researchers will follow the five patients for up to 15 years after therapy in order to get a better picture of just how well gene therapy works. In the meantime, researchers are planning a second trial, this time using patients who have well-controlled HIV viral loads to see if the results are similar.

Radioactive Antibodies

Conventional HIV therapies have resulted in fewer deaths and longer life spans. But as people live longer with HIV, there need to be more therapy choices available to them. We all know that eventually, HIV resistance makes therapies less effective. Over time, HIV medication resistance can eliminate all available conventional therapies, leaving the patient without further treatment choices. For this reason, it is important that scientists look past conventional ways to fight the virus. The following information details the work of three research teams not afraid to look outside the box for the next HIV therapy.

Radioactive Antibodies

For many years, cancer patients have been treated with radioactive substances in hopes of shrinking their cancer and extending their lives. Now nuclear medicine specialists at the Albert Einstein College of Medicine are studying radioactive antibodies and their ability to kill HIV. So far the results have been favorable. In their studies using HIV-infected mice, researchers attached two radioactive isotopes to the antibodies that normally attach to proteins found on the surface of HIV-infected cells. By attaching only to HIV infected cells, the lethal radiation killed the infected cells while leaving the healthy, functioning CD4 cells unharmed. By killing infected cells, HIV replication is slowed or halted, which in turn may slow the progression from HIV to AIDS. In the case of this study, researchers are now looking for a pharmaceutical sponsor that is interested in taking trials to the next step - developing an FDA-approved therapy against HIV.

Understanding Opportunistic Infections

Understanding Opportunistic Infections

The opportunistic infections associated with HIV disease can affect every system in the body, such as:

• Pneumocystis carinii (nu-mo-SIS-tis kah-RIH-neeeye) pneumonia (PCP): pneumonia caused by an organism that has both parasite and fungus properties. It leads to fever, cough, and trouble breathing and can spread to the liver, spleen, and bone marrow. Untreated, the infection causes death.
• Cryptosporidiosis (krip-toh-spo-rid-e-O-sis) and isosporiasis (eye-so-spuh-RYE-uh-sis): intestinal infections caused by parasites that can cause diarrhea, fever, and stomach cramps.
• Cytomegalovirus (sye-tuh-meh-guh-lo-VY-rus): member of the herpesvirus family. Can cause severe infections in people with weakened immune systems. In people with HIV, it can cause an eye infection that may lead to blindness.
• Histoplasmosis (his-toh-plaz-MO-sis): a fungal infection that usually begins in the lungs and causes symptoms such as fever and cough. In people with HIV infection, it can spread throughout the body and lead to problems such as nausea (NAW-zeeuh) and vomiting, joint pain, rash, and sores on the skin.
• Cryptococcal meningitis (krip-toh-KAH-kul mehnin-JY-tis): an infection of the membranes lining the brain and spinal cord caused by a fungus-like organism found in soil. It can cause fever, vomiting, and hallucinations, and can eventually lead to coma or death.
• Cerebral toxoplasmosis (suh-REE-brul tox-oplaz-MO-sis): an infection caused by an organism that affects the brain, heart, lungs, and other vital organs. It can cause headaches, blurred vision, seizures, and brain damage in people with HIV infection.
• Disseminated mycobacterium avium (my-ko-bak-TEER-e-um A-vee-um) complex (MAC): an infection caused by bacteria found in food, water, and soil. Though these germs usually do not make people sick, in those with weakened immune systems they can cause lung disease, fever, night sweats, weight loss, and diarrhea.

For pregnant women infected with HIV, taking antiretroviral drugs during pregnancy and delivering the infant by cesarean section can greatly reduce the risk of a woman passing the infection to her baby. When treatment is given to both mother and infant, the risk of HIV transmission drops by about 75 percent. Doctors also advise that HIV-infected mothers feed their infants formula to prevent passing the virus through breast milk.

Can HIV/AIDS Cause Other Medical Complications?

Can HIV/AIDS Cause Other Medical Complications?

Complications include AIDS-related opportunistic infections; invasive bacterial infection; certain cancers such as non-Hodgkin's lymphoma, Kaposi's (kuh-POE-zees) sarcoma, and cervical ^* cancer; pneumonia; and AIDS dementia (dih-MEN-sha), in which there is impairment of thinking, memory, and concentration. HIV-infected people who use IV drugs are at increased risk for hepatitis ^* C infection, which can lead to severe liver damage and death. People with AIDS also are more likely to develop more severe symptoms and complications from other infections such as syphilis ^* and tuberculosis ^* .

How Can HIV/AIDS Be Prevented?

Researchers are working to develop a vaccine ^* for AIDS. Until one is available, the best means of prevention is avoiding contact with the bodily fluids of someone who is infected. This means:

• avoiding sexual contact; this is the only certain way of preventing HIV infection from heterosexual or homosexual sexual contact
• practicing safer sex (using a latex condom properly every time for vaginal, anal, or oral sex), which reduces but does not eliminate the risk of HIV infection; other forms of birth control such as birth control pills offer no protection against the HIV virus
• avoiding IV drug use and never sharing needles for drugs, steroids, medications, tattooing, or body piercing.

^* vaccine (vak-SEEN) is a preparation of killed or weakened germs, or a part of a germ or product it produces, given to prevent or lessen the severity of the disease that can result If a person is exposed to the germ itself. Use of vaccines for this purpose is called immunization.

How Is HIV/AIDS Treated?

How Is HIV/AIDS Treated?

Receiving treatment as early as possible, before the start of symptoms, increases a person's chances of staying healthier and living longer with HIV infection. Advances in treatment have greatly improved the quality of life, and prolonged life, for many people living with HIV and AIDS. Since the 1980s, various types of medications have been developed to treat AIDS. All of these drugs work by interfering with the replication cycle of HIV; they block the action of certain enzymes ^* that the virus needs in order to make copies of itself. Taking these medicines slows the spread of HIV in a person's body, delaying the onset of AIDS. The class of drugs called protease (PRO-tee-aze) inhibitors (the enzyme that the drug blocks is known as a protease) has proven to be especially effective. These drugs and others are most often used in combinations of three to five medications in a treatment known as highly active antiretroviral (an-tie-REH-tro-vy-rul) therapy (HAART). Other medicines also are used to treat or prevent the opportunistic infections associated with HIV infection. The amount of HIV in the body, called the viral load, is followed with regular blood tests to see how well treatment is working. CD4+ (T-helper) cell counts are followed as well. Over time, the virus can develop resistance to the drugs used to fight it and treatment may have to be changed, so research and development of new medicines is essential.

Taking all medications exactly as they are prescribed is crucial because it can help keep resistance to the medicines from developing. Maintaining general good health, getting enough rest, eating a nutritious diet, not smoking or taking drugs, and visiting the doctor for regular checkups are also important parts of treatment.

Currently there is no cure for HIV and AIDS, so once someone becomes infected that person is infected for life. Experts believe that people with AIDS eventually will die from it, unless death from another cause occurs sooner.

^* enzymes (EN-zimes) are proteins that help speed up a chemical reaction in a cell or organism.

^* cervical refers to the cervix (SIR-viks), the lower, narrow end of the uterus that opens into the vagina.

^* hepatitis (heh-puh-TIE-tis) is an inflammation of the liver. Hepatitis can be caused by viruses, bacteria, and a number of other noninfectious medical conditions.

^* syphilis (SIH-fih-lis) is a sexually transmitted disease that, if untreated, can lead to serious lifelong problems throughout the body, including blindness and paralysis.

^* tuberculosis (too-ber-kyoo-LO-sis) is a bacterial infection that primarily attacks the lungs but can spread to other parts of the body.

* lymph (LIMF) nodes are small,

^* lymph (LIMF) nodes are small, bean-shaped masses of tissue that contain immune system cells that fight harmful microorganisms. Lymph nodes may swell during infections.

^* antibodies (AN-tih-bah-deez) are protein molecules produced by the body's immune system to help fight specific infections caused by microorganisms, such as bacteria and viruses.

^* cultures (KUL-churz) are tests in which a sample of fluid or tissue from the body is placed in a dish containing material that supports the growth of certain organisms. Typically, within a few days the organisms will grow and can be identified.

^* placenta (pluh-SEN-ta) is an organ that provides nutrients and oxygen to a developing baby; it is located within the womb during pregnancy.

About one in four infants born to mothers infected with HIV will be infected with the virus if the mother does not receive treatment during her pregnancy, and the baby after birth, to prevent spread of HIV to the infant. Sometimes infants who are not infected test positive for HIV antibodies in their blood for more than a year because antibodies were passed to the baby through the placenta ^* from the mother. Other tests must be done to help determine whether an infant is truly infected.

(1) The human immunodeficiency virus (HIV) particle (top) travels through the bloodstream and (2) attaches to the receptor on the surface of a lymphocyte (bottom), an immune system cell involved in fighting infections. (3) Genetic material (RNA) from the virus enters the lymphocyte and, (4) with the help of an enzyme called reverse transcriptase, makes copies of itself to be inserted into the genetic material of the host lymphocyte. Drugs known as reverse transcriptase inhibitors act at this step to block the virus' genetic material from copying itself. (5) Copies of the virus' genetic material are inserted into the genetic material of the lymphocyte. (6) This new genetic material in the cell causes the lymphocyte to make the "blueprint" needed for manufacturing new HIV particles. This blueprint contains the code for making virus proteins. An enzyme known as a protease acts to clip the large virus protein molecules into smaller pieces so they can be used to make new HIV particles. Drugs known as protease inhibitors work at this step by interfering with the processing of virus protein. (7,8) New HIV particles are produced and released from the lymphocyte, which is destroyed. These viruses can then travel through the body and enter and destroy other cells.

How Is HIV/AIDS Diagnosed?

How Is HIV/AIDS Diagnosed?

In order to diagnose HIV infection, doctors perform a blood test to look for antibodies ^* to the virus. This test may not show signs of infection until several months after infection occurs. Other tests can detect the presence of the virus in the blood directly. The most common of these uses a technique called the polymerase (pah-LIM-er-ace) chain reaction (PCR). Special cultures ^* of the blood for HIV or a measurement of p24 antigen (AN-tih-jen), a part of the virus's coat, are available but are used less frequently.

A diagnosis of AIDS is made when a person who is infected with HIV develops certain infections or conditions associated with the disease that indicate a weakening of the immune system. AIDS is also diagnosed when the number of CD4+ T-cells in the body drops below a certain level. The level or "count" of these cells can be measured by taking a blood sample.