Video games, social networks, chat rooms, may help prevent HIV

Despite decades of outreach and education efforts that have stabilized human immunodeficiency (HIV) infection rates in the U.S., the pace of new infections among men who have sex with men has been steadily increasing, particularly among young adults and racial and ethnic minorities.

"This is a population that is very used to technology, and there is built-in privacy and immediacy with digital communication that may be especially appealing to men who aren't comfortable disclosing their sexual orientation or their HIV status in a face-to-face encounter," says lead study author Rebecca Schnall, PhD, RN, an assistant professor at Columbia Nursing. "If we want to reduce HIV infection rates, particularly among younger men, we need to explore the use of technology to meet them where they live -- online and on their phones."

A team of researchers led by Schnall conducted a systematic literature review to determine the effectiveness of eHealth interventions for HIV prevention among men who have sex with men. Included studies had to be focused exclusively on eHealth, limited to HIV prevention and testing rather than treatment, targeted only to adult men who have sex with men, written in English, designed as experimental or randomized controlled trials.

One interactive website, Sexpulse, designed by health professionals and computer scientists to target men who seek sexual partners online, successfully reduced high-risk sexual behaviors. Another site, Keep It Up! (KIU), used video games to help reduce rates of unprotected anal sex. A third initiative, a downloadable video game, helped mitigate shame felt by some young men who have sex with men, though the reduction in risky sexual behavior wasn't statistically significant.

Chat rooms may also help prevent HIV, the study found. When a sexual health expert entered a popular chat room to regularly post information about HIV testing and respond to instant messages seeking information on HIV, self-reported HIV testing among participants in the chat room significantly increased.

On social networks such as Facebook and Twitter, popular individuals can spread HIV-prevention messages to their friends and followers. The sharing of information about HIV testing via trusted sources on a social network appeared to increase requests for HIV testing kits, one study found. Another study found that using opinion leaders to disseminate HIV-prevention information via social networks may increase testing rates and bolster condom use during anal sex with partners found online.

"Taken together, the findings from all of these relatively small studies demonstrate the enormous potential of eHealth as a tool to prevent HIV," says Schnall. The task is urgent, she adds. Although men who have sex with men represent about 7 percent of the male population in the U.S., they account for about 78 percent of new HIV infections among males, reinforcing the need for new approaches to prevention. "What we now have is a road map to follow for larger, longer trials that may definitely confirm the effectiveness of eHealth in fighting the spread of HIV."

Antibody-producing cells in people infected with HIV found

By analyzing the blood of almost 100 treated and untreated HIV-infected volunteers, a team of scientists has identified previously unknown characteristics of B cells in the context of HIV infection. B cells are the immune system cells that make antibodies to HIV and other pathogens. The findings augment the current understanding of how HIV disease develops and have implications for the timing of treatment. Researchers at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, led the study.

Using advanced tools to probe B-cell responses to HIV and other pathogens in the laboratory, the researchers found that the B cells that make antibodies to HIV in infected, untreated people are abnormal in that they are more activated, unstable and unresponsive to further stimulation than normal B cells, and also are infrequently observed in healthy people. This finding may help explain why HIV-specific antibodies naturally produced by HIV-infected people do not clear the infection, according to the scientists.

The researchers also observed that when HIV-infected people start antiretroviral therapy, their B-cell response to HIV diminishes quantitatively but improves qualitatively, with normal B cells dominating. However, the earlier a person starts treatment for HIV, the greater their capacity to maintain their pre-treatment level of B-cell response to the virus. An HIV antibody response from primarily normal B cells correlated with both a low amount of virus in the blood (viral load) and a low level of immune activation. According to the scientists, more research is needed to determine whether normal B cells lead to a more effective antibody response than abnormal B cells, and whether HIV-infected people who maintain a low viral load and low immune activation generate a better B-cell response than people who have a higher viral load and a higher degree of immune activation.
Finally, the scientists observed that the B-cell response to HIV is unlike the B-cell responses to other pathogens in the same people. For instance, when researchers exposed the volunteers' blood cells to a tetanus probe, they observed a relatively normal B-cell response. This was likely, they say, because the volunteers had been vaccinated for tetanus before they became infected with HIV, had a normal B-cell response then, and maintained the normal response for years. However, the volunteers' B-cell response to influenza was less normal than their response to tetanus, probably because they had been exposed to certain strains of influenza after acquiring HIV, but more normal than their response to HIV.

Taken together, the study findings add to the growing body of evidence indicating that starting HIV treatment early benefits the health of infected individuals, according to the scientists.

HIV can cut and paste in human genome

A technology that uses the HIV virus as a tool in the fight against hereditary diseases - and in the long term, against HIV infection as well - has been developed in a first of its kind study. The technology repairs the genome in a new and safer manner. "Now we can simultaneously cut out the part of the genome that is broken in sick cells, and patch the gap that arises in the genetic information which we have removed from the genome. The new aspect here is that we can bring the scissors and the patch together in the HIV particles in a fashion that no one else has done before," says one researcher.

For the first time researchers have succeeded in altering HIV virus particles so that they can simultaneously, as it were, 'cut and paste' in our genome via biological processes. Developed at the Department of Biomedicine at Aarhus University, the technology makes it possible to repair genomes in a new way. It also offers good perspectives for individual treatment of both hereditary diseases and certain viral infections: "Now we can simultaneously cut out the part of the genome that is broken in sick cells, and patch the gap that arises in the genetic information which we have removed from the genome. The new aspect here is that we can bring the scissors and the patch together in the HIV particles in a fashion that no one else has done before," says associate professor in genetics Jacob Giehm Mikkelsen from Aarhus University. 'Hit-and-run' technique leaves no traces.

At the same time, the team of researchers from Aarhus have developed a technique that increases the safety of the cutting process, the so-called "gene editing": "In the past, the gene for the scissors has been transferred to the cells, which is dangerous because the cell keeps on producing scissors which can start cutting uncontrollably. But because we make the scissors in the form of a protein, they only cut for a few hours, after which they are broken down. And we ensure that the virus particle also brings along a small piece of genetic material to patch the hole," says Jacob Giehm Mikkelsen. "We call this a 'hit-and-run' technique because the process is fast and leaves no traces."

The researchers have benefited from many years of intense research into HIV as this has e.g. shown that HIV particles can be converted into transporters of genetic information. But when they also become transporters of proteins that are not normally found in the cells, as is the case now, the particles are altered. Virus particles are converted into nanoparticles which carry the substances that can have a direct effect on the treated cells.

HIV infection is one of the areas where the researchers want to make use of the technique, and here the goal is to stop a specific gene from functioning - something that the protein scissors can do. "By altering relevant cells in the immune system (T cells) we can make them resistant to HIV infection and perhaps even at the same time also equip them with genes that help fight HIV. "So in this way HIV can in time become a tool in the fight against HIV," says postdoc and PhD Yujia Cai of the research team.

Barriers to HIV testing in older children

Concerns about guardianship and privacy can discourage clinics from testing children for HIV, according to new research from Zimbabwe. The results of the study, by Rashida A. Ferrand of the London School of Hygiene & Tropical Medicine and colleagues, provide much-needed information on how to improve care of this vulnerable population.

More than three million children globally are living with HIV (90% in sub-Saharan Africa) and in 2011 an estimated 1000 infant infections occurred every day. HIV acquired through mother-to-child transmission around the time of birth is often unsuspected in older children, and the benefits of treatment are diminished in children who develop symptoms of immune system failure before infection is discovered.

Provider-initiated HIV testing and counseling (PITC) involves health care providers routinely recommending HIV testing and counseling when people attend health care facilities. To investigate the provision and uptake of PITC among children between 6 and 15 years old, the researchers collected and analyzed data from staff at 6 clinics in Harare, Zimbabwe.
Among 2,831 eligible children, about three-quarters were offered PITC, of whom 1,534 (54.2%) consented to HIV testing. The researchers diagnosed HIV infection in about 1 in 20 (5.3%) of the children tested, highlighting the need for more effective PITC. HIV infection was also found in 1 out of 5 guardians who tested with a child.

The main reasons that health-care workers gave for not offering PITC were perceived unsuitability of the accompanying guardian to provide consent for HIV testing on behalf of the child, and lack of availability of staff or HIV testing kits. Children who were asymptomatic, older, or attending with a male or a younger guardian were less likely to be offered HIV testing. Male guardians were less likely to consent to their child being tested.

In interviews, health-care workers raised concerns that a child might experience maltreatment if he or she tested positive, and showed uncertainty around whether testing of the guardian was mandatory and whether only a parent (if one was living) could legally provide consent. When parents were alive but not present, seeking consent from another adult raised ethical concerns that a positive HIV test in a child would disclose the HIV status of a parent who hadn't provided consent.

The study, which was funded by the Wellcome Trust, did not explore the reasons for refusal of HIV testing by clients. Also, because the relationship of the child to the accompanying adult was not available, the appropriateness of the guardian could not be independently ascertained.

Lead author Dr. Rashida Ferrand from the London School of Hygiene & Tropical Medicine said: "The fear of the stigma faced by the child and their family seems to be discouraging caregivers from testing children for HIV. However, with improved clarity of guidelines, engagement with staff, and organisational adjustments within clinics, it should be possible to harness the commitment of health-care workers and properly implement HIV testing and counseling."

In an accompanying Perspective, Mary-Ann Davies and Emma Kalk of the University of Cape Town, who were uninvolved in the study, point out that "The fact that >90% of infected children had a previous missed opportunity for testing indicates suboptimal pediatric PITC coverage in most routine settings," and call for "clear HIV testing policies for children and guidance on guardianship, together with training of [health-care workers] on such policies."

Men living with HIV have a lower risk of prostate cancer

Incidence of prostate cancer is significantly lower among men living with HIV, investigators from California report.

“We found a 27% reduced risk of prostate cancer among HIV-positive men after adjustment,” comment the authors. “HIV-positive men were more likely to be tested and were diagnosed with lower-stage cancers and lower PSA [prostate specific antigen].”

Thanks to antiretroviral therapy, an ever-increasing proportion of people with HIV are now living into older age. The diseases of ageing are therefore an increasingly important cause of illness among people living with HIV. For instance, diagnoses of prostate cancer increased fivefold among men living with HIV in the US between 1991 and 2005. Despite this, infection with HIV has been associated with a 20 to 25% reduction in the risk of being diagnosed with prostate cancer. It has been suggested that this is due to lower screening rates.

Investigators from Kaiser Permanente in California wanted to see if infection with HIV really was associated with a reduced risk of being diagnosed with prostate cancer and if this could be attributed to lower levels of PSA screening.

They therefore designed a case-controlled study matching each HIV-positive participant with ten HIV-negative controls who entered care in the same year, were of a similar age and were receiving care at the same centre.

Incidence of prostate cancer was compared between the HIV-positive and HIV-negative men, adjusting for potential confounders such as age, race, smoking, drug or alcohol use, diabetes and testosterone levels.

Data were also collected on rates of PSA screening for men enrolled in Northern California.

Study participants entered care after 1996 (Southern California) or 2000 (Northern California). The study population included 17,424 HIV-positive and 182,799 HIV-negative men. They were followed for a mean of 4.2 and 5.0 person-years/subjects, respectively. The groups were of similar age. However, the men living with HIV were more likely than the HIV-negative men to be white and to report a history of smoking (39 vs 23%), alcohol abuse (12 vs 7%), drug abuse (15 vs 4%) and testosterone deficiency (13 vs 1%). Prevalence of diabetes and obesity did not differ by HIV status.

Almost two-thirds of HIV-positive men (62%) were in the men who have sex with men (MSM) risk group. Only 42% of the men living with HIV were taking antiretroviral therapy at the time they entered the study. By the end of follow-up, 76% were taking HIV treatment, mean CD4 count was 466 cells/mm3 and 61% had a viral load below 500 copies/ml.

Prostate cancer was diagnosed in 74 HIV-positive and 1195 HIV-negative men. Differences according to HIV status were observed. Men living with HIV were more likely to be diagnosed with less advanced cancers (state II, 95 vs 89%; stage III-IV, 5 vs 11%) and to have localised (93 vs 83%) rather than regional/distal (3 vs 14%) cancers. Recent PSA levels were lower among men living with HIV (10 vs 17).

Overall incidence of prostate cancer was 102/100,000 person-years for men living with HIV compared to 131 per 100,000 person-years for HIV-negative men. After controlling for potential confounders, men living with HIV had a 27% reduction in the risk of prostate cancer (RR = 0.73; 95% CI, 0.57-0.92). The association between HIV infection and a reduced risk of prostate cancer was strongest for more advanced cancers (stage III/IV, RR = 0.28; 95% CI, 0.009-0.90; regional/distal cancers, RR = 0.28; 95% CI, 0.11-0.68). However, men living with HIV also had a reduced risk of less severe forms of cancer (stage II, RR = 0.77; 95% CI, 0.60-1.01; localised cancers, RR = 0.81; 95% CI, 0.63-1.05).

These differences could not be explained by lower levels of screening among men living with HIV. In fact, a higher proportion of HIV-positive than HIV-negative men had undergone PSA screening by the age of 55 (91 vs 86%, p < 0.001).

The investigators restricted their analysis to the sub-set of men in Northern California who had PSA testing. After adjustment, men living with HIV had a significantly reduced risk of prostate cancer (RR = 0.55; 95% CI, 0.39-0.80).

“Our results suggest that the observed lower incidence of prostate caner among HIV-positive men…is attributable to factors other than differences in PSA screening,” comment the investigators.

No HIV-related characteristics were associated with prostate cancer risk. For both HIV-positive and HIV-negative men, risk of the cancer increased with age (p < 0.001) and was also associated with black vs white ethnicity.

The investigators call for further research to investigate why men living with HIV have a lower risk of prostate cancer.

Soy sauce molecule may unlock drug therapy for HIV patients

For HIV patients being treated with anti-AIDS medications, resistance to drug therapy regimens is commonplace. Often, patients develop resistance to first-line drug therapies, and are forced to adopt more potent medications. Virologists at the University of Missouri now are testing the next generation of medications that stop HIV from spreading, and are using a molecule related to flavor enhancers found in soy sauce, to develop compounds that are more potent than other.

"Patients who are treated for HIV infections eventually develop resistance to the drugs that prevent an effective or successful defense against the virus," said Stefan Sarafianos, associate professor of molecular microbiology and immunology in the University of Missouri School of Medicine, and a virologist at the Bond Life Sciences Center at MU. "EFdA, the molecule we are studying, is less likely to cause resistance in HIV patients because it is more readily activated and is less quickly broken down by the body as similar existing drugs."

In 2001, a Japanese soy sauce company inadvertently discovered the EFdA molecule while trying to enhance the flavor of their product. The flavor enhancer is part of the family of compounds called "nucleoside analogues" which is very similar to existing drugs for the treatment of HIV and other viruses. EFdA samples were sent for further testing, which confirmed EFdA's potential usefulness against HIV and started more than a decade of research.

EFdA, along with eight existing HIV drugs, is part of the class of compounds called nucleoside reverse transcriptase inhibitors (NRTIs). NRTIs "hijack" the HIV replicating process by "tricking" building blocks inside the virus. Since EFdA appears similar to those building blocks, the virus is misled into using the imposter, which prevents HIV replication and halts the spread of the virus.

In their latest study, Sarafianos and his colleagues, including researchers from the University of Pittsburgh and the National Institutes of Health, helped define how EFdA works on a molecular level. Using virology techniques and nuclear magnetic resonance spectroscopy (NMR), they pieced together the exact structure and configuration of the molecule. Compounds developed by Sarafianos and his team currently are being tested for usefulness as potential HIV-halting drugs with pharmaceutical company Merck.

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."

Sustanon 250

Sustanon 250, a strong anabolic with pronounced androgenic activity, is considered by many as one of the most powerful combinations of testosterone.

Originally developed by the international drug firm Organon as an alternative to hormone replacement therapy (HRT), this anabolic androgenic steroid contains four different testosterone esters: Testosterone propionate (30 mg), testosterone phenylpropionate (60 mg), testosterone isocaproate (60mg), and testosterone decanoate (100 mg) that stimulate a fast yet extended release of testosterone.

Sustanon 250 has the chemical name of 17ß-hydroxyandrost-4-en-3-one and can be detected over a period of 2-3 months. This steroid has an active life of nearly 2-3 weeks and the molecular formula of Sustanon 250 is C19H28O2.

Sustanon 250 is one of the most commonly recommended drugs for the development and maintenance of reproductive tissues such as the prostate, epididymis, seminal vesicles, testes, and penis even at low doses. Sustanon 250 also has the ability to prevent degeneration of existing muscles in wasting diseases and is prescribed to individuals diagnosed with HIV/AIDS. Sustanon 250 can easily promote muscle function, muscle size, body strength, and nitrogen retention gains and also has the potential to improve plasma concentrations of Testosterone, Dihydrotestosterone, Oestradiol (estrogen hormone), and Androstenedione. Most athletes and bodybuilders use this steroid to experience improvements in the level of sexual function, such as libido and erectile function and reduction in the levels of serum LDL-C, HDL-C, and triglycerides.

When used as per medical advice, Sustanon 250 can even stimulate improvements in levels of hemoglobin and Hematocrit without resulting in any clinically relevant changes in liver enzymes and PSA. Sustanon 250 is commonly used by athletes as a bulking drug that leads to exceptional strength and muscle mass gains. Sustanon 250 does convert to estrogen but it is slightly more tolerable than testosterone cypionate or enanthate. This is primarily because blood levels of testosterone build slowly with the use of this steroid and it means that side effects do not happen fast.

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.