Category: Viruses

Central obesity is a risk for HIV-associated cognitive impairment

Because effective antiviral therapy can suppress HIV replication and prolong the life of HIV-infected patients to that approaching non-infected individuals long term complications of antiviral therapy acquire particular importance. Among these are neuro-cognitive disorders.

Neurocognitive impairment, ranging from mild deficits to severe dementia, occurs in about half of HIV-infected individuals. A recent study by McCutchan et al has suggested that increased waist circumference was associated with increased prevalence of neuroognitive impairment in a subgroup of HIV-infected patients followed up in the CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) study. They found that central obesity, but not more generalized increases in body mass (BMI), was associated with a higher prevalence of neurocognitive impairment (NCI) in HIV+ persons. Diabetes appeared to be associated with NCI only in older patients.

These findings are similar to those reported in the non-infected populations with central obesity – known as metabolic syndrome. the mechanisms for these findings are unclear. However as central obesity and metabolic syndrome appear to be common in HIV-infected patients receiving antiviral therapy these findings may have important implication for patients.The authors concluded that avoidance of antiretroviral drugs that induce central obesity might protect from or help to reverse neurocognitive impairment in HIV-infected persons.

Research on the long term metabolic effects of anti-retroviral treatment, which has focused on the mechanisms for increased incidence of cardiovascular disease seen in patients on treatment should be widened to include neurocognitive impairment and its relations to central fat accumulation.

Oral human papillomavirus infection more common in US males

Almost 7 percent of American men and women are infected orally with the human papillomavirus (HPV), new research reveals, with men showing significantly higher infection rates than women. Indeed among those between the ages of 14 and 69, men seem to face a nearly threefold greater risk than women for oral HPV infection.

The study was part of the ongoing National Health and Nutrition Examination Survey (NHANES). To better understand that connection, Gillison’s team sifted through data on nearly 5,600 men and women collected between 2009 and 2011 NHANES. All NHANES participants had been examined in person, during which all were tested for HPV.

In a study published in the Journal of the American Medical Association (JAMA) on Janury 26, 2012 Dr. Maura Gillison, chair of cancer research in the department of viral oncology at Ohio State University’s Comprehensive Cancer Center in Columbus reported  an overall oral HPV infection rate of 6.9 percent, with HPV-16 being the most common type.

Oral HPV incidence varied with age, however, with peak rates occurring among those between the ages of 30 and 34 (at 7.3 percent) as well as among men and women between 60 and 64 (11.4 percent). Overall, oral HPV infection hit the 10 percent mark among men. Among women it was just shy of 4 percent.

While those with a history of smoking, heavy drinking, and/or marijuana use appeared to face a higher risk for infection, sexual behavior also plays a key role in upping a person’s risk. For example, while those who had never had sex faced less than a 1 percent risk for oral HPV infection, prevalence hit 7.5 percent among those who were sexually active. And the greater the number of sexual partners, the higher the risk.

Calls to immunise teenage boys after huge rise in throat cancer

Cases of oropharyngeal cancer have more than doubled to over 1,000 annually since the mid-1990s after remaining stable for many years, Professor Hisham Mehanna, director of the Institute of Head and Neck Studies in Coventry reports.

The Department of Health requested the latest figures from Professor Hisham Mehanna, who has surveyed the incidence of HPV-related oropharyngeal cancer in the UK and other countries. “We are experiencing a very significant rise in oropharyngeal cancer. It used to be rare in our practice – now [head and neck cancer] is the most common cancer we see. All the studies show there is a strong association with oral sex.” It is also occurring in younger patients.

More than 70 per cent of cases are caused by human papilloma virus (HPV), compared with less than a third a decade ago. HPV is transmitted during sex, including oral sex and also possibly spread by open-mouth kissing. HPV is the main cause of cervical cancer in women, affecting almost 3,000 women a year in the UK.

Currently women are offered HPV vaccine to prevent cervical cancer. The quadrivalent vaccine also protests against genital warts in both women and also their male partners and is now being advocated by the Department of Health.

The US is considering offering HPV vaccine to men.

HIV highly homogeneous in early infection

Current findings suggest that the mucosal barrier is the major site of viral selection in sexual transmission of human immunodeficiency virus type 1 (HIV-1), transforming the complex inoculum to a small, homogeneous founder virus population. In a recent study from Zurich the authors analyzed HIV-1 viral seqiuences in the C2-V3-C3 region in 145 patients with characteristics  primary HIV-1 infection. They found that  the meedian viral diversity within env was 0.39% (range 0.04%–3.23%). Viral diversity did not correlate with viral load, but it was slightly correlated with the duration of infection.

They also found that  neither transmission mode, gender, nor STI predicted transmission of more heterogeneous founder virus populations. Only 2 patients (1.4%) were infected with CXCR4-tropic HIV-1 with a duakl-tropic R5/X4-tropic–mixed population. The other patients were infecetd by the CCR5-trophic virus which targets the macrophage series.

The authors concluded that transmission of multiple HIV-1 variants might be a complex process that is not dependent on mucosal factors alone. CXCR4-tropic viruses can be sexually transmitted in rare instances, but their clinical relevance remains to be determined. These results have imprtant implications for vaccine development.

An alternative explanation for these results, not discussed by the authors, is that the individuals were infected by a small number or even a single CCR5-trophic virus which subseqeuntly mutates to the complex virus soup that is seen in long-term infected subjects.

Vitamin D deficiency and cardiovascular disease: more information needed

Vitamin D deficiency is common in the general population. It has been linked with hypertension, myocardial infarction, and stroke, as well as other cardiovascular-related diseases, such as diabetes, congestive heart failure, peripheral vascular disease, atherosclerosis, and endothelial dysfunction.

Yet a recent publication in The Annals of Internal Medicine  has highlighted the conflicting nature of the information available, as it relates to increased cardiovascular disease, and has called for proper prospective randomised studies.

Vitamin D deficiency, along with cardiovascular disease, diabetes and some malignancies are more commonly seen in HIV infected patients compared to age-matched controls. While the mechanism for the vitamin D deficiency in HIV infection is still unclear, this deficiency has been shown to be associated with an increased prevalence of type 2 diabetes mellitus.

In a cross sectional study of their HIV cohort in Pennsylvania, USA, Guaraldi and colleagues showed an almost doubling (OR 1.85 CI 1.03-3.3) of diabetes mellitus in those with vitamin D levels below 20 ng/ml compared to those with normal levels. The authors controlled for vitamin D supplementation, sex, age, body mass index (BMI), and hepatitis C, all of which are known to effect glucose metabolism.

We urgently need prospective studies to confirm these findings and to answer the question if vitamin D supplementation will prevent these putative complications of vitamin D deficiency.

Antiretroviral prophylaxis: a defining moment in HIV control

According to an editorial by Salim Abdool Karim in the Lancet  a defining moment in the global AIDS response has been reached. The discourse is no longer about HIV prevention or HIV treatment; it is now about HIV control through the implementation of antiretroviral treatments as key components of combination interventions.

Barely a year ago, visions of HIV control would have been considered far-fetched. The impetus for this change in mindset, which has been building since the XVIII International AIDS Conference in Vienna last year, emanates from the compelling evidence that antiretroviral drugs prevent HIV infection in the general heterosexual population, which is released this week and presented at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Rome by the Partners PrEP and Botswana TDF2 trials.

The Partners PrEP trial, involving 4758 HIV discordant couples from Kenya and Uganda, found that daily oral tenofovir disoproxil fumarate (TDF) and TDF-emtricitabine reduced HIV transmission by 62% and 73%, respectively. The Bostwana TDF2 trial, in 1200 heterosexual men and women from the general population, found that daily oral TDF-emtricitabine reduced HIV transmission by 63%.

Both these are of a similar order of magnitude to that seen with male circumcision and is probably caused by a significant reduction of HIV in the genital tract.

see fig 1 for comparison between different prevension strategies

Several issues were raised by the authors that need further research. There is now no doubt that antiretroviral drugs prevent HIV infection. However, important scientific questions remain. Does the inclusion of emtricitabine in pre-exposure prophylaxis (PrEP) formulations provide sufficient additional benefit to warrant the additional costs and side-effects? Are levels of effectiveness and safety similar for daily use and use-with-sex of PrEP? Do the safety, effectiveness, cost, and acceptability profiles of oral and topical PrEP merit implementation of both formulations? Does PrEP lead to masking of HIV acquisition that is then revealed once PrEP is withdrawn?

UK NHS finally accepts to use quadrivalent HPV vaccine in girls

From next September girls in the United Kingdom being vaccinated against human papillomavirus (HPV) will receive Gardasil, the vaccine that protects against genital warts as well as cervical cancer.

The Joint Committee on Vaccination and Immunisation recommended that the HPV vaccine should be offered routinely to girls aged 12 to 13 years and in a catch-up programme to those up to 18 years of age. Since then, 1.5 million young women and girls have been protected.

GlaxoSmithKline, which has been providing the Cervarix vaccine to the UK’s HPV vaccination programme since it launched in September 2008, said in a statement that it did not take part in the latest tendering exercise to provide a vaccine for the programme because the government made it clear that it wanted to protect girls against the types of HPV that caused cervical cancer and those that caused genital warts.

Gardasil, which is supplied by Sanofi Pasteur MSD, protects against HPV types 16 and 18, which cause 70% of cervical cancers, and HPV 6 and 11, which are responsible for nine in 10 cases of genital warts. Cervarix protects against HPV types 16 and 18.

When the UK programme launched, health campaigners criticised the choice of Cervarix as being short sighted and a missed opportunity (BMJ 2008;336:a451, doi:10.1136/bmj.a451)

Worldwide Gardasil has been the vaccine of choice. It has been selected by health authorities in the United States, Australia, New Zealand, Canada, Switzerland, Italy, Spain, and Sweden for regional or national vaccination programmes against cervical cancer.

Research from Australia has shown that cases of genital warts have nearly disappeared since 2007 when the national vaccination programme against cervical cancer using Gardasil was introduced (Sexually Transmitted Infectionsdoi:10.1136/sextrans-2011-050234). The study found that new diagnoses of genital warts among women under 21 years attending a sexual health centre in Melbourne fell from 18.6% in 2007-8 to 1.9% in 2010-11 and in heterosexual men aged under 21 from 22.9% to 2.9%. During the period before the introduction of the vaccination programme, new cases of genital warts rose by 1.8%.

Use of human papillomavirus (HPV) vaccine causes dramatic fall in genital warts

An important new study by a team of researchers working in a sexual health clinic in Melbourne, Australia has shown that 4 years after a government funded program of vaccinating girls and women aged 12-18 there was a dramatic decline in new cases of genital warts in heterosexual women and also of men with a new diagnosis of genital warts. Cases of genital warts attending the Melbourne Sexual Health Centre fell from 18.6% of all new diagnosis in women under 21 in 2007-2008  to 1.9% in 2010-2011. Interestingly there was a similar dramatic fall in new cases of genital warts in men under 21 over the same time period from 22.9% to 2.9%. The odds ratio per year for diagnosis of genital warts that was adjusted for number of sexual partners from July 2007 until June 2011 in women <21 years was 0.44 (95% CI 0.32 to 0.58) and in heterosexual men aged <21 was 0.42 (95% CI 0.31 to 0.60)  – a fall of over 55% in both sexes.

There was no drop in the incidence of new genital warts diagnosis in women aged over 30 or in men who have sex with men adding weight to the authors’ conclusions that the fall in new wart cases in younger men and women was a consequence of vaccination. It is argued that a reduction in new infections in young women had resulted in a reduced pool of infection and hence also caused a similar drop in their male sexual partners.

The Australian government was providing the vaccine free to all girls and women aged 12-18 from 2007 until the end of 2009. Since then free vaccine has been only offered girls aged 12-13.  The vaccine used in Australia contains antigens from HPV 6 and 11 which are the commonest HPV genotypes associated with genital warts as well as HPV 16 and 18 associated with cervical cancer.

Unfortunately the quadrivalent vaccine is not the one chosen for use by the Department of Health in the UK. A recent study which we reported earlier showed that the quadrivalent vaccine is more cost effective than the bivalent vaccine currently recommended for use in the UK.

 

US Committee recommends HPV vaccine for men

Human papilloma virus (HPV) causes warts but also is the underlying cause of various cancers, particularly cervical cancer in women.  HPV vaccines are now available and recommended for young women to prevent cervical cancer, and in the case of quadrivalent vaccine also genital warts. [see our news item: Quadrivalent wart vaccine would prevent high cost of care for genital warts ] The vaccine is more effective if administered to children aged 11-12 years, before they become sexually active

Now a study published in the New England Journal of Medicine showed that the quadrivalent vaccine can prevent intraepithelial neoplasia, a precursor of anal cancer, in young gay men. anal intraepithelial neoplasia associated with the HPV types linked to cervical cancer (HPV 16 and 18) were reduced by 55% in the vaccinated group. Consequently the US Advisory Committee on Immunisation Practice has recommended the roll out of vaccination to all children aged 11-12, regardless of sex.

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Quadrivalent wart vaccine would prevent high cost of care for genital warts

In a recent study by Desai et al published in the journal Sexually Transmitted infection it was estimated that the annual cost of treating genital warts in general practice and genitourinary clinics was approximately £16.8 million. Most of this is potentially preventable if the government chooses the quadrivalent Human Papilloma Virus (HPV) vaccine which includes HPV typed 6 and 11 which are the commonest cause of genital infections in addition to types 16 and 18 which are the main causes of cervical cancer. Unfortunately the Department of Health currently advocates vaccination with a vaccine containing types 16 and 18 only which would not protect against genital warts and is also more expensive.