The Body Covers: The 9th Conference on Retroviruses and Opportunistic Infections
Selected Highlights From Retrovirus
January 1, 1980
Many companies are also working on changing the formulations or combining some of the 17 approved anti-HIV drugs so that more anti-HIV medications can be taken only once or twice a day. This continuing development of medications is great news.
One of the most exciting new drugs presented was TMC125, a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) manufactured by Tibotec-Virco. There were two abstracts presented, one reporting on very early results in a tiny group of 12 naive patients and another reporting on results with 16 treatment-experienced patients.
When 900 mg of TMC125 was given twice a day for seven days to 16 treatment-experienced patients in Belgium (session 4) who had highly NNRTI-resistant virus and were currently failing on an NNRTI-containing regimen, it demonstrated significant antiviral potency and was well tolerated.
When the same dose of TMC125 was used with treatment-naive patients in Amsterdam (session 5), the initial rate of decline in plasma HIV-1 during the first week of therapy was similar to that of patients on a five-drug regimen during the same period of time. Quite remarkable results, however, only 12 patients were in the trial and these were the results after only one week.
SCH-C, by Schering-Plough, also had a lot of people talking. In a small, first study in humans, SCH-C, which blocks a chemokine receptor known as CCR5, appeared to be safe and effective in lowering viral loads. The study, which is ongoing, has only 12 patients. The reported data was based on results gathered after only 10 days. More studies will be needed.
Click here to see the description of this new drug from the Schering-Plough site.
DPC 083 (083) is a NNRTI with potent activity against wild-type HIV and greater potency against NNRTI-resistant mutants than efavirenz. The objective of this study was to compare the tolerability of three doses of DPC 083 to the standard dose of efavirenz in naive patients. Pharmacokinetic and efficacy data were also analyzed. In this ongoing, multi-center study, DPC 083 was found to be effective and well tolerated in patients who had never used any anti-HIV medication.
Some of the specific findings presented at the conference were pretty intriguing, though. Here are the highlights:
An analisys of HIV/AIDS surveillance data from 25 U.S. states (474-M) found that HIV progression was most severe in people who are diagnosed "late" (defined as receiving an HIV diagnosis a year or less before receiving an AIDS diagnosis). Nearly half of all HIV diagnoses are late, according to the study -- meaning that these patients are already at a major disadvantage when it comes to the effectiveness of life-saving antiretroviral medications. The key to preventing disease progression, these researchers note, is painfully simple: more people need to get tested early, before CD4 counts drop too low and AIDS develops.
Researchers in British Columbia (476-M) have found that patients whose CD4 levels were below 200 were more than twice as likely to die from AIDS-related causes as patients with CD4 levels above 200. According to their province-wide study of HIV-positive men and women, the odds of death stayed the same regardless of the patients' AIDS diagnosis or the type of anti-HIV drugs they used.
HAART is even more essential for HIV-positive people over age 50 than for those who are younger, according to a Johns Hopkins study of 2,500 patients at an urban clinic (472-M). The study found that while the mortality rate of older patients who don't use HAART is more than twice that of patients under 50, death rates are almost identical between the two age groups when both are taking HAART. This means that, relatively speaking, HAART is far more effective in prolonging the lives of the over-50 crowd, which makes early diagnosis and treatment of older patients all the more essential.
Only about half the deaths among HIV-positive patients can be directly attributed to AIDS-related causes, according to two independent studies conducted on opposite sides of the world. One of the studies, a nationwide survey of HIV clinics in France (753-W), revealed that cytomegalovirus, pneumonia, mycobacterial infections and toxoplasmosis were the most common AIDS-related causes of death. The most common non-AIDS-related causes of death were hepatitis C, non-AIDS-defining cancers, cardiovascular disease and unrelated infections. The other study, a small review of HIV-positive patients in the California Bay Area (752-W), found that old age, history of injection-drug use and low CD4-cell counts were found to be significant factors in speeding HIV progression. The French study found that medication side effects accounted for only one percent of all deaths -- one-third the rate of deaths attributed to accidents and alcohol abuse.
In one retrospective study (777-W) at Columbia Presbyterian Medical center, researchers sought to discover what has never been proven. Do women have the same virologic and CD4 response to HAART as men? In this small look back, women in the Columbia study were started on therapy with baseline CD4 counts similar to those of the men in the study. These women were more likely than men to reach an undetectable viral load. Both the men and women maintained a similar durable virologic and CD4 response to HAART.
A few other studies showed that gender does influence viral load, with women consistently having lower viral loads than men at similar stages of HIV infection. This has been shown in previous studies as well. One study (775-W) did a retrospective review looking for evidence of gender on viral loads. The researchers looked at publications in MEDLINE, AIDSLINE, Dissertation Abstracts Online and related proceedings of annual AIDS meetings over the past seven to ten years. They found that women consistently had lower viral loads than men at similar stages of disease -- in fact up to two-to-six-fold lower viral loads than men, particularly early in HIV infection, following HIV seroconversion. These findings clearly push for more research and, researchers say, perhaps treatment guidelines for when to initiate HAART should be adjusted according to gender.
Men who have sex with men (MSM) who were recently infected with HIV were shown to have more unprotected sexual partners than MSM who were not infected, according to a local University of California-San Francisco study (772-W). The finding is alarming, but not particularly surprising: After all, the more partners a person has, the more likely he or she is to become infected. The more frightening fact coming out of this survey may be the complacency among many MSM about HIV: 34 percent of the men who had recently been infected revealed that they had been less inclined to use condoms because effective treatment for HIV was so readily available.
A large survey of some of the cities hardest hit by HIV (773-W) found that young men who have sex with men (YMSM) are also very likely to use illegal drugs. Two-thirds of the nearly 3,500 YMSM studied said they took drugs, such as cocaine, crystal meth and ecstasy. Six out of every ten used marijuana and 29 percent said they had used drugs frequently in the past six months. Drug use is a risky endeavor because it impairs judgement and, in the case of injection drugs, may directly expose a person to HIV. More importantly, though, when you combine the prevalence of drug use among YMSM with the risks involved in unprotected sex between men -- with an increasingly casual attitude toward HIV infection -- you have at least a partial explanation for why the HIV-infection rates among gay men are once again on the rise.
For the first time ever, researchers have found undeniable proof that HIV can indeed be transmitted through a human bite (770-W). Brazilian researchers reported on the case of a 31-year-old HIV-positive man who, during an epileptic seizure in 1999, bit his mother on the arm. His mouth, according to the report, did have blood in it at the time, and the bite was severe enough that the mother required stitches. Forty days later, she was diagnosed with HIV. Although there have been a few cases of HIV transmitted this way previously, this is the first time the viruses have been molecularly confirmed as being related.
Of greater alarm may be the first documented case of a person contracting HIV through a blood transfusion that had been screened for HIV (768-W). The method of screening that was used, a commonly used procedure known as "nucleic acid amplification testing of minipools" (MP-NAT), apparently failed to detect a very small viral load in blood taken from a donor who had been very recently infected (and thus tested HIV-negative). The finding confirms that there is an incredibly small risk of HIV transmission through blood transfusions, even after the blood has been screened. According to the Red Cross, however, those odds are about one in 1.5 million (less than .00006 percent).
Another update on the risks of contracting HIV through blood transfusions (769-W): The CDC reported that, of the 774,467 people in the U.S. with AIDS through December 2000, about 9,000 of them (a little over 1 percent) contracted HIV, directly or indirectly, through receipt of HIV-infected blood -- with most of those cases occurring before HIV screening of the blood supply began in 1985. A third of those infected were over 60, and a quarter were black. On the plus side, the number of transfusions leading to HIV infection is less than the CDC expected -- although, admittedly, that could be because it doesn't include people who were infected before 1985 and have not yet developed AIDS. The majority of these people are no longer living.
A study of male and female inmates (767-W) at four New York prisons revealed that HIV incidence numbers have steadily dropped from 1988 to 2000. HIV infection among male inmates has dropped especially sharply, from 17.6% of the entire inmate population in 1988 to 4.7% in 2000. Though the study didn't investigate the reasons for this drop, its authors conclude that the most likely explanation is the drop in injection drug use over the same 12-year period. (See www.thebody.com/hepp/jan02/spotlight.html.)
413-W, 414-W, 415-W, 416-W) attest to tenofovir's strength beyond treatment-experienced patients, for whom tenofovir was originally tested. One new study that many HIV specialists seemed quite excited about, showed tenofovir to be a good choice for treatment-naive patients. Also encouraging are findings that tenofovir causes a minimal number of side effects -- comparable to that of patients taking a placebo instead. And because it's taken once a day it makes tenofovir a very attractive drug.
T-20, still in phase III trials and with good success at lowering viral loads for treatment-experienced patients, is part of a new class of anti-HIV drugs called fusion inhibitors. It continues to make strong showings in clinical trials. One nationwide study (418-W) shows that T-20 is effective in patients starting NNRTI therapy after becoming resistant to protease inhibitors. Another (417-W) finds that doubling the dosage of the drug (which is currently administered in two injections, twice a day) would allow patients to halve the number of daily injections to one every 12 hours, without sacrificing any of T-20's safety or effectiveness.
Two large-scale studies of HIV patients on triple-combination therapy in British Columbia (749-W, 750-W) have led researchers to the realization that the more experience a doctor has in treating HIV-positive patients, the more likely his or her patients are to live longer. The only real caveat to this finding was among the poor: After all, the researchers note, it's harder to get access to triple-combination therapies when you're making less money, no matter how knowledgeable your doctor is or how great socialized medicine is in Canada. True, all of this is only logical, but it's always nice to have research data backing that logic up -- it makes it easier to get lawmakers to do something about it.
Based on surveys of HIV healthcare workers (doctors, nurses and physician assistants) in Atlanta, Los Angeles, Baltimore and Miami, researchers found that HIV-experienced physicians with a background in primary care appear to address or emphasize preventive aspects of care like drug or condom use to a greater extent than those physicians with a background in infectious disease (751-W.) However, infectious disease doctors report more familiarity with HIV/AIDS care guidelines and are more likely to obtain information from medical journals and scientific conferences and less likely to use pharmaceutical representatives as a source of information. (This last bit was a scary little finding! It's terrifying to discover that there are any physicians who rely on drug salespeople for choosing a drug for patients!)
There was, however, one important new study evaluating the effect of adherence to HAART on the treatment of patients with primary HIV infection (544-T). Not surprisingly, these patients' viral loads were more likely to drop below 50 if they reported high adherence two months after initiating therapy.
Another study had an unexpected outcome: Despite theories that increased telephone contact with patients regarding their medications would improve adherence, this was found not to be the case (540-T). Most patients in this study -- both those who received standard adherence help and those who received additional support via the telephone -- already had high levels of adherence, so the additional telephone contact had no appreciable impact on reported adherence levels or viral loads. While not startling, this information should help HIV/AIDS practitioners and administrators allocate resources more efficiently when it comes to providing adherence help.
A quick summary of other findings presented at this year's poster session on adherence to therapy follows:
Patients in a study (541-T) in the south of France were provided with three individual counseling sessions about HAART regimens by specially trained nurses. Nearly all of the patients increased their adherence to HAART and decreased their viral load levels. This intervention would be relatively easy to provide and had great results.
Most patients who showed high levels of adherence to a mock Medication Electronic Monitoring System (MEMS) trial (542-T) were more likely to have low viral load levels after several months of HAART than those who failed the mock MEMS trial.
In a California study (546-T), patients with low adherence did not have a higher risk for developing drug-resistant mutations because they generally discontinued treatment early on. Highly adherent patients who continued therapy with a viral load over 100 developed drug resistance with greater frequency than less-adherent patients who discontinued therapy.
Odd that you would need a study to prove this, but patients in this Johns Hopkins University Medical Center study (547-T) who went from not abusing substances to becoming substance abusers where more likely to have decreased adherence, poor suppression of viral load, and decreased CD4 cell counts. Those who stopped abusing substances had better adherence, were more likely to suppress viral load and increased their CD4 cell counts.
While much of this seems to be just common sense, it is always good to have solid scientific evidence to support clinical practice and medical policy.
One study at an HIV clinic (69) compared current HIV-positive patients with the same clinic's patients in 1993, before HAART became available. It found that neurological problems (sensory neuropathy) are more common in today's patients than they were in 1993. This is particularly true for patients who had taken a dideoxynucleoside drug such as ddI, and older patients. So while HAART permits HIV-positive people to live longer, their senses (meaning their touch, smell, etc., not their intelligence) can be impaired in the process.
More serious, however, is the understanding of the growing risk of heart (cardiovascular) disease in HIV-positive people. Several studies examined the risk for such complications. They found that patients with undetectable HIV who were taking Indinavir tended to suffer from chronic inflammation and other heart disease risks (694-T). Other studies showed that taking any protease inhibitor increased patients' risk for developing other types of heart disease, ischemic cardiovascular disease (695-T), and myocardial infarction (698-T). Sounds grim, but all studies noted that many patients risked heart disease from other problems (e.g., being overweight, smoking, etc.) as well. Bottom line: try to live as healthy as possible, especially if you are taking anti-HIV medication.
One long-term study of HIV-positive patients who began medications with severely damaged immune systems, but recovered immune system function with HAART therapy, showed that recovery continued even after medications to prevent MAC (mycobacterium avium complex) were stopped (630-W). Other studies (634-W, 631-W) confirmed these findings and one (631-W) even showed similarly low rates of bacterial pneumonia (lung disease) after stopping preventative medication (Azithromycin) for that disease. HAART apparently can repair some patients' immune systems well enough that medications to prevent toxoplasma encephalitis (brain infection) may be safely withdrawn. However, this is not true for all patients, so doctors need to carefully test each patient before deciding whether to stop preventative treatments (633-W).
While HAART can help HIV-positive people live longer, hospitalization occurs frequently for some people. Why? One study of HIV-positive patients admitted to an Illinois hospital over the course of two years found that active substance abusers were less likely to take their medications on schedule and therefore more likely to wind up in the hospital for HIV-related problems. Older HIV-positive patients, who also had hepatitis C (liver disease), didn't spend as much time in the hospital than the first group and when they did, it was for other medical problems (e.g., diabetes) (636-W). The moral? Take your medications on schedule and don't do drugs and you just might stay out of the hospital.
Amidst staggering infection numbers and some governments' (read: South Africa's) unwillingness to offer nevirapine to pregnant women, there's still some good news coming out of sub-Saharan Africa (S26). A survey of clinics and hospitals in 11 southern countries found that HIV testing had increased anywhere between 25 and 90 percent or more over the past two years. The increase is largely thanks to a program launched by the Elizabeth Glaser Pediatric AIDS Foundation, which instituted HIV-prevention services in each of the 70 surveyed clinics and hospitals back in 1999, hoping to making inroads against mother-to-child transmission of HIV. Each site offers counseling, HIV testing, and nevirapine when needed; the 70 clinics and hospitals involved reach an estimated 42,000 pregnant women. The survey's findings raise hopes that prevention and treatment services will indeed go far to help HIV-infected women, children and families.
With the good news comes the bad: Testing and prevention efforts may be working, but the bottom line as we all know is that too many people in developing nations aren't getting the meds they need. A presentation on Uganda (S25) discusses the great difficulties that HIV-positive Ugandans -- currently 8 percent of the population -- have getting proper treatment. Anti-HIV drugs, where they're available (which is not in too many places) and when people can afford them (which is hardly ever), are too often not monitored by doctors, because patients get medications from friends and relatives rather than from pharmacies or clinics. This means that many people who take meds often are not properly educated on the importance of adherence, and, of course, are not given viral load or CD4 testing to gauge drug effectiveness, and don't have many choices when it comes to picking the wisest drug regimen for them. The end results are low adherence, low levels of success, and higher AIDS death tolls.
In hopes of eventually creating an AIDS vaccine for China, researchers in New York and Beijing (760-W) analyzed HIV strains in 96 patients scattered throughout the country. They discovered four distinct mutations of the HIV-1 bug. Interestingly, though China is a massive country, all four appeared to be closely related, indicating that the spread of HIV throughout the country was still in its earliest phases. This news is both good and bad: Good because fewer HIV mutations make it easier to develop effective prevention and treatment efforts; bad because this may be only the tip of the infection iceberg in a country that's already estimated to have well over half a million HIV-positive citizens.
In Southern Europe, meanwhile, treatment is getting more complicated. Researchers in Spain (759-W) are discovering more and more variety in HIV strains in the region, perhaps because of southern Europe's proximity to West Africa, with which Spain and Portugal still have very strong ties (what with all that colonialism that went on back in the 18th, 19th and early 20th centuries). All this co-mingling of different virus types could result in an even greater number of new strains, which may make it tougher for HIV treatment specialists to determine the most effective drug therapies for their patients.
Especially worrisome is the still rare but growing number of so-called "super-infection" cases, in which a person has been infected with two or more different strains of the virus. (A report by researchers in Geneva and London (757-W) discusses one such case.) Super-infection (also called re-infection) is so dangerous because it has the potential to thwart several different treatments at once; when anti-HIV drugs beat down one of the viral strains in a patient, another strain might simply slide in and take its place. There is a small but growing trove of evidence that these super-infection cases are rare but increasing, which could put a serious dent in efforts to treat existing HIV-positive patients and develop vaccines to prevent future outbreaks.
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