Category: HIV

New sensitive DNA assay for PCP infection

Pneumocystis jirovecii pneumonia (PCP) is a leading cause of morbidity and mortality in HIV and other immunocompromised patients. Currently the commonly used PCR for diagnosing P. jirovecii will miss some organisms by staining methods. The authors of a study published in Clinical Microbiology and Infection  developed a new assay using the same targeted genes.

This assay was compared with the currently used PCR and other conventional assays (Giemsa staining and immunofluorescence assay).   Brochoalveolar lavage (BAL) sample collected from human immunodeficiency virus (HIV)-infected (n = 66) and non-HIV (n = 36) immunocompromised patients presenting with fever, dyspnoea, cough and pulmonary infiltrates was tested by all the assays. Pneumocystis jirovecii was diagnosed with Giemsa-stained smear, immunofluorescence assay, conventional single-round and nested PCR, and the new PCR in 46 (45.1%), 53 (52.0%), 69 (67.6%), 74 (72.6%), 87 (85.3%) and 91 (89.2%) patients, respectively.

The new PCR could detectP. jirovecii DNA in BAL fluids two to three orders of magnitude more dilute than conventional PCR.  Although both conventional and new PCR assays were highly specific for diagnosing P. jirovecii, the new PCR yielded more positive results than conventional PCR among BAL samples that were negative by both Giemsa stain and immunofluorescence assay. Hence, the new PCR offered a more sensitive detection of P. jirovecii infection and colonization than conventional PCR.

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.

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?

Delay in diagnosis of HIV can cut 15 years off your life

Current treatment with antiviral drugs has changed a previously fatal disease into a chronic condition where those infected can expect to live a normal and healthy life for many years.

Forward projections from a number of large cohorts have, however, suggested that with current treatment regimens patients may still have a slightly shorter life expectancy than uninfected persons. This is because patients with HIV appear to experience diseases associated with aging such as heart attacks, diabetes and cancer at a younger age,

A recent study from a UK-based large cohort by May and colleagues confirm these projections with men expected to do worse than women. They estimated that for an average 20 year old man HIV decreases life expectancy by 18.1 years compared with 11.4 years for women. This may reflect life-style differences between the sexes (alcohol, smoking) but may also be because women of child-baring age are more likely to be diagnosed early during routine antenatal screening.

Their study showed that persons starting antiviral therapy with a low CD4 count of less than 100 – which is sign of severe immunological damage – rather than earlier (CD4 200-350) lose over 15 years of life. Currently guidelines recommend starting antiviral therapy when the CD4 falls at or below 350.

While there are problems with making accurate projections into the future this research further highlights the importance of routinely offering and testing for HIV at all clinical settings in order to identify the infection early and before any significant immunological damage has taken place.

See BMJ 2011:343-d6016

Doi:10.1136/bmj.d6016

Update on ongoing project funded by STIRF

An assessment of patients’ satisfaction with their HIV care

Project STIRF 012

People with HIV are living longer, healthier lives due to advances in treatments.  Their healthcare needs, therefore, have changed and doctors and nurses need to have the knowledge and skills to meet those needs.   The project funded by STIRF aims to find out what patients attending an HIV outpatient clinic want from the service and how well it is provided. The team started out by trying to find out whether there was an established way of measuring HIV patients satisfaction with there care and if a questionnaire already existed that could be used. Some of questionnaires which had been used in the past did not seem to be relevant to the patients today.

Since then the team have held focus groups with patients to ask them what questions they would like included and what would motivate them to fill in a questionnaire. Once the questionnaire has been tested on a small group of people, a larger survey will be conducted and the results analysed, to find out how happy HIV patients are with their outpatient service and what they would like to see changed. We hope to find the right tools so that a listening exercise can be turned into an effective plan of action.