Category: New treatments

Daily pri-exposure prophylaxis (PrEP) prevents HIV infection in high risk gay men

Daily HIV medicine taken by men who have sex with men (MSM) reduces risk of HIV infection by 86% as was reported by Molina J-M, and colleagues in the ANRS Ipergay trial  at the Conference on Retroviruses and Opportunistic Infections held in Seattle, USA in 2015 (23LB.).

Molina et al reported the final results of a three year study which randomised MSM who were negative for HIV to either take daily HIV prophylaxis with two anti-retroviral drugs in a single tablet immediately or deferred for 1 year.

The study showed that those taking the drugs on a daily basis have a 86% reduction in the risk of being infected by HIV than MSM not taking the drug (p=0.0001). The trial was stopped in October of 2014 and all participants in the  deferred group were offered pre-exposure prophylaxis (PrEP)

As a Lancet editorial commented:

The science is now clear: oral pre-exposure prophylaxis (PrEP) with a coformulation of tenofovir disoproxil fumarate and emtricitabine (Truvada) significantly reduces the risk of HIV infection among individuals at high risk of HIV infection.

The news that PrEP has shown consistent efficacy among those who take it as prescribed should be a cause for celebration, and galvanise action to ensure access to PrEP for those who could benefit the most. But almost 3 years since the US Food and Drug Administration approved tenofovir–emtricitabine for PrEP little is being done on implementation.

With more than 2 million new HIV infections every year worldwide, it is time for that to change.

Start HIV treatment regardless of CD4 count

A large international study (INSIGHT START) published in the New England Journal of Medicine has found that starting antiretroviral therapy immediately after human immunodeficiency virus (HIV) diagnosis rather than waiting until a patient’s CD4+ count has declined is of considerable benefit.

The results of the study were also released at the International AIDS Society conference in Vancouver, Canada, on 20 July.

Currently most authorities strongly recommend starting anti-HIV once CD4+ count drops to below 350 cells per cubic millimetre. Until the INSIGHT START study there was no randomized trials  showing the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic HIV infection who have a CD4+ count of more than 350 .

START study conducted in 35 countries randomly assigned 4,685 HIV positive patients to either receive immediate antiretroviral therapy (median CD4+ of 650) or wait until their counts fell to below 350.

After a mean follow up of 3 years the study found that 42 patients in the immediate-initiation group died, as compared with 96 patients in the deferred-initiation group  (95% confidence interval, 0.30 to 0.62; P<0.001). Reduction in deaths were largely from tuberculosis, Kaposi’s sarcoma, and malignant lymphomas – conditions that can occur in HIV-infected individuals with only moderately damaged immune systems.

Currently the WHO requires all patients with HIV to be treated CD4+ of 500 or less. WHO may need to extend that to treating anyone at diagnosis. This would not only benefit the individual but by reducing viral shedding in body secretions reduce transmission and hence have a public health benefit. Moreover some of the costs of starting early would be offset by not needing to perform repeated CD4+ counts.

Important new research on lymphogranuloma venereum (LGV) in gay men in the UK

Lymphogranuloma venereum (LGV), previously predominantly a tropical disease, re-emerged in Western Europe in 2003, and has arguably now regained endemic status in many countries. It remains largely contained within in a population of men who have sex with men (MSM) with high rates of other sexually transmitted infections (STIs) including HIV, though a first female case was reported in Sexually Transmitted Infections in 2012.

A recent series of papers in Sexually Transmitted Infections sheds further light on the risk factors for rectal LGV in men who have sex with men in the UK, the key symptoms and ways in which LGV presents to the clinician, and pitfalls in the currently recommended treatment and prevention strategies.

Moreover, microbiological  characteristic of LGV repeaters using surveillance data has convinced Rönn and colleagues that behaviour alone does not explain reinfection, which they see as related to centrality in sexual networks.

Together these four articles add important information on the clinical presentation, epidemiology and treatment of LGV in MSM.

Need and acceptability of human papillomavirus (HPV) vaccination in men

HPV vaccination of young women with the quadrivalent vaccine (HPV4) resulted in a dramatic fall in genital warts and cervical cancer rates. However rolling out a similar vaccination in young men has been hampered by arguments that  male HPV4 vaccination programmes exceed cost-effectiveness thresholds.

Unlike the USA and Australia, European countries do not include men in HPV vaccination programmes, instead focusing on achieving expanded coverage among women to promote herd immunity.

Yet there is  evidence that HPV4 vaccination offers substantial clinical benefits to men and is cost effective among men who have sex with men (MSM). MSM have largely been excluded from mathematical models. A recent study in the journal Sexually Transmitted Infections has shown that HPV related conditions such as anal/genital warts and rectal infections are likely to be profoundly underdiagnosed among MSM in most European cities. The paper concluded that there is an urgent need to improve sexual healthcare tailored to MSM at risk for STIs.

There is also the argument  for a gender-neutral (universal) approach to vaccination.

In the same issue of STI a meta-analysis shows that there are currently a number of obstacles to acceptability of HPV vaccination in  men. They concluded that Public health campaigns should aim to promote positive HPV vaccine attitudes and awareness about HPV risk in men. The paper recommended interventions to promote HPV vaccination for boys and to overcome  obstacles to HPV vaccine acceptability for men.

Trichomonas vaginalis – a neglected STI with major global health implications

Trichomonas vaginalis (TV) is the most prevalent curable sexually transmitted infection (STI) globally. Yet at least 80% of TV infections are asymptomatic, though even asymptomatic infections are a public health concern.

In addition to the risk of transmission to sex partners, TV infection has been associated with as much as a 2.7-fold increase in the risk of HIV acquisition, a 1.3-fold increase in the risk of preterm labour, and a 4.7-fold increase in the risk of pelvic inflammatory disease.

A recent review in the journal Sexually Transmitted Infections (STI) highlights the current knowledge of the global epidemiology of TV infection. These include sex differences in the incidence and prevalence of infection, and the potentially important role of female sex hormones, and the menstrual cycle in mediating TV susceptibility and natural history.

WHO has estimated that over half the 248 million new TV infections each year occur in men. By contrast, 89% of prevalent TV cases are found among women. Biological differences between the sexes contribute to these striking differences between men and women.

There has also been an increased understanding of the mechanisms underlying resistance to metronidazole – the current sole drug available to eradicate the organism.

Recent innovations in detection, including the availability of nucleic acid amplification tests (NAATs), have improved our understanding of the natural history of TV infections. These innovations and our increased understanding of this common sexually transmitted infection should help us combat the global epidemic in TV.

Rising gonorrhoea antimicrobial resistance in Europe

A recent report by the European Centre for Disease Prevention and Control has highlighted the danger that rising antibiotic resistance may mean that soon gonorrhoea may become an untreatable disease in some parts of Europe.

According to the report the most worrying result is the increase in the percentage of isolates with decreased susceptibility to cefixime and the increase in the number of countries where this phenotype was identified between 2009 and 2010. [Fig 1]


Fig 1. European Centre for Disease Prevention and Control

Patient characteristics of isolates with decreased susceptibility did not differ greatly when compared to the overall population, except for age: patients with decreased susceptibility to cefixime were more likely to be older.

There is some evidence that the rates of ciprofloxacin and azithromycin resistance have both decreased since 2009. However they remain worringly high across Europe (53% and 7%, respectively).

Similar results for cefixime – which is the first line drug therapy in many centres – have been reported by the European gonococcal antimicrobial surveillance programme (Euro-GASP) – Fig 2


Cephalosporine resistance in gonococcal isolates 2009 – Euro-GASP

Dramatic drop in health spending according to OECD

Growth in health spending slowed or fell in real terms in 2010 in almost all OECD countries, reversing a long-term trend of rapid increases, according to OECD Health Data 2012.

In real terms average health spending has declined by over 6% compared to the start of the millenium.

Overall health spending grew by nearly 5% per year in real terms in OECD countries over the period 2000-2009, but this was followed by zero growth in 2010. Preliminary figures for a limited number of countries suggest little or no growth in 2011. The halt in total health spending in 2010 was driven by a fall of 0.5% in public spending for health, following an increase of over 5% per year in 2008 and 2009.

While government health spending tended to be maintained at the start of the economic crisis, cuts in spending really began to take effect in 2010. This was particularly the case in the European countries hardest hit by the recession.

CROI 2012 Review web cast

Register now for web-cast education on the most important topics covered by CROI (Conference on Retroviruses and Opportunistic Infections) in February 2012. The web-cast will cover the following topics

  1. Review the latest data on anti-retroviral medication.
  2. Describe studies using HCV protease inhibitors in HIV infected patients.
  3. Describe the latest data on treatment of TB and opportunistic infections in HIV patients.
The target audience are

  • Physicians
  • Physician Assistants Nurses
  • Nurse Practitioners
  • Other health care professionals caring for people with HIV

Registration deadline is May 1.

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.