HIV-positive women respond well to HPV vaccine

HIV-positive women respond well to a vaccine against the human papillomavirus (HPV), even when their immune system is struggling, according to newly published results of an international clinical trial. The study's findings counter doubts about whether the vaccine would be helpful, said the Brown University medical professor who led the study. Instead, the data support the World Health Organization's recommendation to vaccinate women with HIV.

HPV causes cervical and other cancers. The commonly used HPV vaccine  had not been tested in seriously immune-suppressed women with HIV, said Dr. Erna Milunka Kojic, associate professor of medicine at the Warren Alpert Medical School of Brown University and The Miriam Hospital. Despite the WHO recommendation, she said, skeptics have wondered whether the vaccine would be safe and helpful for women with weakened immune systems who were already likely to have been exposed to HPV through sex. Vaccines are often less effective in HIV-positive people.

To address that debate, Kojic's study, dubbed "AIDS Clinical Trials Group Protocol 5240," measured the safety and immune system response of the vaccine in HIV-positive women aged 13 to 45 with a wide range of immune statuses. In the vast majority of the 315 volunteers who were vaccinated at sites in the United States, Brazil, and South Africa, the vaccine built up antibodies against HPV and posed no unusual safety issues during the 28 weeks they were each involved.

"The vaccine works for HIV-infected women in terms of developing antibodies," Kojic said.

Co-author Dr. Susan Cu-Uvin, professor of public health and of obstetrics and gynecology at Brown, said women with HIV are especially susceptible to cervical cancer from HPV because their weakened immune systems are less able to clear the virus. That makes vaccinating HIV-positive women especially important, so long as it's safe and they respond.

"This is a very safe vaccine. It doesn't have any systemic side effects among these women who are already taking medicine for other conditions."

Response across the board

To investigate that response in the context of HIV, the study grouped women by their CD4 cell count, a measure of immune system health. Group A had CD4 counts above 350, group B rested between 200 and 350. Group C was composed of women with counts below 200, the defining level of AIDS for which response to an HPV vaccine had not yet been studied.

 "Quadrivalent" vaccine, in that it protects against four types of HPV (6, 11, 16, and 18). Each group in the study, therefore, had four measures of "seroconversion," or the buildup of a significant army of antibodies against each type of HPV. The researchers determined that seroconversion in at least 70 percent of patients for each HPV type would define success.

"Seroconversion proportions at week 28 among women in CD4 stratum A were 96 percent, 98 percent, 99 percent, and 91 percent for HPV types 6, 11, 16, and 18 respectively; in stratum B, 100 percent, 98 percent, 98 percent, and 85 percent; and in stratum C, 84 percent, 92 percent, 93 percent and 75 percent for each type respectively," the authors wrote.
Seroconversion rates were clearly lower for women with the weakest immune systems, but still high enough to be worthwhile, Kojic said. And although some of the women in the study had already been exposed to at least one type of HPV, only 1 in 25 had been exposed to all four, suggesting that even older, sexually active women can benefit from vaccination.

The extent of the benefit, she acknowledged, is not yet clear because the trial did not measure the vaccine's efficacy in preventing cancers. It only measured safety and the number of patients who had the desired immune system response. But that response has been shown to be effective in other studies of other populations of women.

What is clear from the study is that the vaccine produced no more side effects or problems than any vaccine typically does.

"Comparing vaccine reactions, this is a very safe vaccine," Kojic said. "It doesn't have any systemic side effects among these women who are already taking medicine for other conditions."

Kojic said she hopes that by confirming that women with HIV are responsive to the vaccine without unusual adverse effects, more doctors will vaccinate HIV-positive patients.

Low cholesterol in immune cells tied to slow progression of HIV

People infected with HIV whose immune cells have low cholesterol levels experience much slower disease progression, even without medication, according to University of Pittsburgh Graduate School of Public Health research that could lead to new strategies to control infection.

The Pitt Public Health researchers found that low cholesterol in certain cells, which is likely an inherited trait, affects the ability of the body to transmit the virus to other cells. The discovery, funded by the National Institutes of Health (NIH).

When HIV enters the body, it is typically picked up by immune system cells called dendritic cells, which recognize foreign agents and transport the virus to lymph nodes where it is passed to other immune system cells, including T cells. HIV then uses T cells as its main site of replication. It is through this mechanism that levels of HIV increase and overwhelm the immune system, leading to AIDS. Once a person develops AIDS, the body can no longer fight infections and cancers. Prior to effective drug therapy, the person died within one to two years after the AIDS diagnosis.

"We've known for two decades that some people don't have the dramatic loss in their T cells and progression to AIDS that you'd expect without drug therapy," said lead author Giovanna Rappocciolo, Ph.D., an assistant professor at Pitt Public Health. "Instead the disease is much slower to progress, and we believe low cholesterol in dendritic cells may be a reason."

The discovery was made possible by using 30 years of data and biologic specimens collected through the Pitt Men's Study, a confidential research study of the natural history of HIV/AIDS, part of the national NIH-funded Multicenter AIDS Cohort Study (MACS).

"We couldn't have made this discovery without the MACS. Results like ours are the real pay-off of the past three decades of meticulous data and specimen collection," said senior author Charles Rinaldo, Ph.D., chairman of Pitt Public Health's Department of Infectious Diseases and Microbiology, and professor of pathology. "It is thanks to our dedicated volunteer participants that we are making such important advances in understanding HIV, and applying it to preventing and treating AIDS."

Medications called combination antiretroviral therapy (ART) disrupt the viral replication process and can delay the onset of AIDS by decades.

However, even without taking ART, a small percentage of people infected with HIV do not have the persistent loss of T cells and increase in levels of HIV after initial infection. They can sometimes go many years, even more than a decade, without the virus seriously compromising the immune system or leading to AIDS.

Through the Pitt Men's Study/MACS, eight such "nonprogressors" were assessed twice a year for an average of 11 years and compared to eight typically progressing HIV-positive counterparts.

Dr. Rappocciolo and her colleagues found that in nonprogressors, the dendritic cells were not transferring the virus to T cells at detectible levels. When taking a closer look at these dendritic cells, the researchers discovered that the cells had low levels of cholesterol, even though the nonprogressors had regular levels of cholesterol in their blood. A similar finding was shown for B lymphocytes, which also pass HIV to T cells, leading to high rates of HIV replication.

Cholesterol is an essential component of the outer membranes of cells. It is required for HIV to replicate efficiently in different types of cells. None of the study participants were taking statins, which are cholesterol-lowering medications that some people take to prevent vascular problems when cholesterol in their blood is too high.

When HIV was directly mixed with the nonprogressors' T cells in the laboratory, those T cells became infected with the virus at the same rate as the T cells of the regularly progressing, HIV-positive participants. Indeed, T cells from the nonprogressors had normal levels of cholesterol.

"This means that the disruption is unlikely to be due to a problem with the T cells, further supporting our conclusion that the slow progression is linked to low cholesterol in the dendritic cells and B cells," said Dr. Rappocciolo.

"What is most intriguing is that dendritic cells in the nonprogressors had this protective trait years before they became infected with HIV," Dr. Rinaldo said. "This strongly suggests that the inability of their dendritic cells and B cells to pass HIV to their T cells is a protective trait genetically inherited by a small percentage of people. Understanding how this works could be an important clue in developing new approaches to prevent progression of HIV infection."

Testosterone Cypionate - still the best possible mass builder in the world.

Testosterone is the prime male androgen in the body, and as such still the best possible mass builder in the world. It has a high risk of side-effects because it readily converts to a more androgenic form (DHT) in androgen responsive tissues and forms estrogen quite easily. But these characteristics also provide it with its extreme anabolic tendencies. On the one hand estrogen increases growth hormone output, glucose utilization, improves immunity and upgrades the androgen receptor, while on the other hand a testosterone/DHT combination is extremely potent at activating the androgen receptor and eliciting major strength and size gains. While not always the most visually appealing result, there is no steroid on earth that packs on mass like testosterone does.

Testosterone Cypionate is a single-ester, long-acting form of testosterone. Due to the length of its ester (8 carbons) it is stored mostly in the adipose tissue upon intra-musuclar injection, and then slowly but very steadily released over a certain period of time. A peak is noted after 24-48 hours of injection and then a slow decline, reaching a steady point after 12 days and staying there for over 3 weeks time. Of course most users of anabolics will not find adequate benefit in the use of this steady-point dose, so Testosterone Cypionate is normally injected once a week, making the very lowest dose higher than half the peak dose at any given time. This is roughly the starting blood level as well. A long-acting testosterone ester is a must-have in any mass-building cycle. As such Testosterone Cypionate is a very decent product.

Personally I have more affinity for Testosterone Enanthate, but few users will note any real difference between the two products, and both remain a better buy than their popular counterpart sustanon 250, which is a poor choice of testosterone in my opinion. It makes sense that a user simply opts for which one is most readily available at the time. They sell for roughly the same price, and are almost equally good. So most North and South-American users will usually opt for the use of a cypionate, as it is more available in those regions, whereas Europeans and Asians will probably prefer the enanthate version.

A long-acting testosterone ester may be the best for all your mass-building needs, but its not an easy product to use. Because of the extreme length of action (3-4 weeks) one cannot easily solve occurring problems by simply discontinuing the product, as it will continue to act and aggravate side-effects over extended periods of time. In regards to damage control and post-cycle therapy, some familiarity with the use of ancillary drugs is required prior to using a long-acting testosterone product. Nolvadex and Proviron will come in very handy in such cases and post-cycle HCG and clomid or Nolvadex will be required as well to help restore natural testosterone. Frequency of side-effects is probably highest with this type of product.

While most will tell you it's a waste to not use testosterone, as it will take ages longer to build proper mass, these are all points to take into consideration. Testosterone is a product that is heavily used by beginners and veterans alike and justly so. Those who fear they may never understand the proper use of ancillary drugs, may want to suck it up and invest in some propionate or suspension testosterones instead. These are much shorter acting and easier to control, but they do need to be injected once every two days, whereas this type of ester will impart great gains with a single weekly injection. Something to keep in mind.

Testosterone is the most powerful compound there is, so obviously its perfectly fine to use it by itself. With a long-acting ester like Testosterone Cypionate doses of 500-1000 mg per week are used with very clear results over a 10 week period. If you've ever seen a man swell up with sheer size, then testosterone was the cause of it. But testosterone is nonetheless often stacked. Due to the high occurrence of side-effects, people will usually split up a stack in testosterone and a milder component in order to obtain a less risky cycle, but without having to give up as much of the gains. Primobolan, Equipoise and Deca-Durabolin are the weapons of choice in this matter. Deca seems to be the most popular, probably because of its extremely mild androgenic nature. But Deca being one of the highest risks for just about every other side-effects, I probably wouldn't advise it. If Deca is used, generally a dose of 200-400 mg is added to 500-750 mg of testosterone per week.

Primobolan is sometimes opted for, and can be handy since it doesn't aromatize, which will make the total level of water retention and fat gain a lot less than with more test or with Deca for example. Unfortunately, its mild nature combined with a lack of estrogen make Primobolan a very poor mass builder. Again, doses of 300-400 mg are used. I would actually suggest a higher dose, but with the current prices for Primo I don't think it would be very popular. My personal preference goes out to Equipoise. Androgenically its not that much stronger than Deca because it has next to no affinity for the 5-alpha-reductase enzyme and is only half as androgenic as testosterone. Its twice as strong as Deca, mg for mg, and has a lower occurrence of side-effects. It has some estrogen, but not a whole lot so it actually tends to lean a person out rather than bloat him up as Deca will. It also increases appetite, which promotes gains, and improves aerobic performance, which may be wishful as testosterone normally has an opposite effect.

Of course Testosterone Cypionate can be stacked with any number of compounds apart from these, but these make the best match. When stacking with testosterone, one needs to look at what the other compound can bring. Either it has a characteristic that testosterone doesn't have, or its nominally safer. The testosterone will bring all the mass, so adding another steroid to enhance mass alone, is futile. More testosterone is the best remedy for that.

One needs to be familiar with a host of other compounds when using long-acting testosterone esters however. First of all, anti-estrogens. The rate of aromatization of testosterone is quite great, so water retention and fat gain are a fact and gyno is never far off. If problems occur one is best to start on 20 mg of Nolvadex per day and stay on that until problems subside. I wouldn't stay on it for a whole cycle, as it may reduce the gains. In terms of an aromatase blocker, testosterone is one of the few compounds where Proviron may actually be preferred over arimidex. The proviron will not only reduce estrogen and can be used for extended time on a testosterone cycle, it will also bind with great affinity to sex-hormone binding proteins in the blood and will allow for a higher level of free testosterone in the body, thus improving gains.

Usually 50-100 mg will suffice, the lower end is preferred for maximal results since estrogen plays a key role in gains, but those more worried about estrogen should opt for a higher dose. For those worried about androgenic side-effects (hair loss, prostate hypertrophy, deepening of voice), one can utilize the hair loss treatment finasteride. This blocks the 5-alpha-reductase enzyme and stops the conversion of testosterone to the more androgenic compound DHT. I'm not a big fan of this, because DHT reduces estrogenic bloat, increases free levels of testosterone and is a very potent androgen that is 3-4 times stronger than testosterone. Those worried about hair loss however, may want to opt for arimidex as their anti-aromatase, since Proviron is a form of DHT after all. After a cycle, mainly due to the high aromatization and increased levels of estradiol in the blood after discontinuing, natural testosterone levels will be severely suppressed. This means steps need to be taken to assure the quick return of natural testosterone, or we stand to lose a lot of the gains we made while using testosterone. Since it's a non-toxic, potent mass-builder its mostly used in long 10-12 week cycles. So some testicular shrinkage will have occurred too. Its very important that people see that HCG and Nolvadex/clomid are essential as a post-cycle therapy, and that both are equally important in achieving our goal. HCG injections should be started the last week of the cycle and continued for 3-4 weeks, using 1500-3000 IU every 5-6 days. HCG will act as an alternative to LH and start the endogenous testosterone cycle, thereby increasing testicle size once again. Then about 2 weeks after the last shot of testosterone is given, Nolvadex/Clomid cycle should be started. 40 mg of Nolva or 150 mg of Clomid per day for two weeks, followed by two more weeks with either 20 mg of Nolva or 100 mg of Clomid per day should be adequate. Always remember that HCG is suppressive of natural testosterone itself and should be discontinued at least 2 weeks prior to finishing Nolvadex/Clomid.

Oxymetholone reduces wasting among HIV patients.

Oxymetholone, an anabolic steroid, appears to be effective in countering wasting among HIV-positive patients taking highly active antiretroviral therapy (HAART).

This finding results from a double-blind, randomised, placebo-controlled trial at the University of Essen, and the University of Bonn, Germany. Eighty-nine HIV-positive women and men participated.

Chronic involuntary weight loss is a serious problem among patients on HAART. The alterations in energy metabolism and endocrine regulation cause loss of lean body mass (LBM) and body cell mass (BCM).

There has been partial restoration of LBM in studies among HIV-positive men undergoing androgen replacement therapy, or treatment with recombinant growth hormone. However, these treatments have largely been ineffective among eugonadal individuals.

In the present study, the men and women with wasting were given Oxymetholone 50 mg twice (BID), or three times daily (TID), or placebo for 16 weeks, followed by open-label treatment. Endpoints were body weight, bioimpedance measurements, and appetite.

The clinicians found that Oxymetholone produced a significant weight gain of 3.0 ± 0.5 kg in the TID group, and 3.5 ± 0.7 kg in the BID group, while patients in the placebo group gained an average of 1.0 ± 0.7 kg. Body cell mass increased 3.8 ± 0.4 kg in the BID group and 2.1 ± 0.6 kg in the TID group. This corresponded to 12.4T and 7.4% of baseline BCM, respectively.

The patients taking Oxymetholone reported significant improvements in their appetite and food consumption, plus a reduction in feeling weak. The most important adverse event was liver-associated toxicity.

Overall, 35% of patients in the TID, 27% of patients in the BID Oxymetholone group, and no patients in the placebo group, had a greater than five times baseline increase for alanine aminotransferase during the double-blind phase of the study.

Clinicians concluded that “the BID (100 mg/day) regimen appeared to be equally effective as the TID (150 mg/day) regimen in terms of weight gain, LBM and BCM and was associated with less, but still significant liver toxicity.”

The Effects of Oxandralone on Body Weight and Composition in Patients with HIV-Associated Weight Loss

A variety of anabolic steroids are in use to help counteract the severe loss of body weight that effects many patients with advanced HIV disease. Studies have previously shown that HIV-related wasting causes the destruction of body cell mass (or BCM: active muscle and tissue) while leaving fat stores relatively untouched, so treatments that preserve or help regain healthy, active body tissue are obviously important.

This open-label observational study enrolled 572 patients (527 men and 45 women) with a mean age of 40 years and a mean baseline weight of 68.1 kilograms. Patients were on stable antiretroviral regimens, had documented weight loss, and had no active opportunistic infections or cancers. All patients were treated daily with 20 mg of oxandrolone, an anabolic steroid in pill form. Study visits were scheduled after 1, 2, 4, 8 and 12 months. At each visit, patients were weighed, asked to assess their appetite, sense of well-being, and energy levels, and underwent bioelectric impedance assay (BIA) analysis. BIA measures body cell mass, amount of water in the body, and fat vs. muscle ratio.

Only 26 of the 572 patients had completed the full year-long study before Geneva, but their results, and the interim results from other the patients, were promising. Among the first 26, mean increases in total body weight (and body cell mass, listed in parentheses) were as follows:

• Month 1 2.4 kg total (1.4 kg of which was BCM)
• Month 2 2.8 kg (1.5 kg)
• Month 4 4.4 kg (2.1 kg)
• Month 8 5.4 kg (3.1 kg)
• Month 12 6.1 kg (3.5 kg) 

Patients' self-assessment also improved, with increased appetite and sense of well-being, and oxandralone was generally well-tolerated, with fewer than one percent of patients experiencing liver function test abnormalities, a side effect associated with anabolic steroids. Most side effects were managed with dose reductions.