Viagra users may experience more condom failure

Men who use Viagra and other erectile dysfunction drugs are four times more likely to experience condom breakage than other men, report American researchers in the September issue of Sexually Transmitted Infections. However a separate study conducted by the same team did not find the same association, which would need to be confirmed by other research. In the first study, the researchers used newspaper and internet advertisements to recruit a convenience sample of 440 men who used condoms for vaginal sex. The self-completion questionnaire focused on the most recent occasion they had sex. Just under one in ten of the men had used an erectile dysfunction drug on that occasion. For 12% of these men the condom broke, compared to 5% of men who didn’t use an erectile dysfunction drug. Men reporting a longer duration of intercourse were also more likely to report condom breakage. However, in multivariate analysis, which controls for the skewing effect of other factors, erectile dysfunction drug use remained significant - users were four times more likely to report condom breakage (adjusted odds ratio 4.04, 95% confidence interval 1.06 - 15.41). The researchers suggest that as Viagra and related drugs increase swelling during an erection, it is plausible that condoms become more tight-fitting. They say that users of these drugs may need to be advised to use condoms that are large enough for an enhanced erection. Moreover, users should be made aware that having sex for longer is associated with condom breakage. However the same team of researchers published a separate study earlier this year in the Journal of Sexual Medicine, which did not find the same association. In this study, a different group of 705 men were recruited via a website selling sexual paraphernalia. Although most men were heterosexual, some were reporting on anal sex. Men who used recreational drugs were excluded. Once again, the men were asked about the last time they used a condom for penetrative sex. Seven per cent of men reported using an erectile dysfunction drug. Condom breakage was rarely reported in this sample, and was no more commonly reported by erectile dysfunction drug users. On the other hand, users were actually more likely to report the condom slipping off or erection problems during sex. The researchers concluded from this that while Viagra and similar drugs may improve men’s erections, they do not always eliminate all erection problems, especially those associated with condom use. The researchers believe that their studies highlight the importance of further research into the implications of using erectile dysfunction drugs

Read more!

Three-quarters of HIV-positive US prisoners stop anti-HIV drugs after release from jail

Few HIV-positive prisoners in the US continue to take HIV treatment once they are released from jail, Canadian and US investigators report in the online journal PLoS One. “We are concerned about the deleterious effects of intermittent therapy in light of the SMART data and the possibility of the development of resistance”, comment the investigators. They continue, “our study…highlights the need to support continuous antiretroviral therapy and the importance of continuity of care services for HIV infected persons who enter the cycle of incarceration.” HIV is a significant health problem in US prisons especially as it has been estimated that up to a quarter of HIV-positive individuals in the US will be imprisoned at some point. Prisons are an important site of HIV care, which should be provided in accordance with US treatment guidelines. However, many individuals who initiate HIV treatment whilst incarcerated interrupt are unable or unwilling to continue their therapy after their release. There is little information on the effects of antiretroviral therapy for prison inmates. Investigators therefore performed a retrospective study involving 512 individuals who were imprisoned in the San Francisco county jail over a ten year period between 1996 and 2005. Information was obtained on their use of antiretroviral therapy and changes in their CD4 cell count and viral load. All the individuals were incarcerated at least twice (median five instances), with each sentence averaging a little over three months. Just over half of the prisoners (51%) were African American, and the vast majority (86%) were male. Over three-quarters (76%) of individuals interrupted their HIV treatment after their release from prison. Only 15% took continuous HIV treatment and 9% refused antiretroviral altogether. Individuals taking continuous or intermittent HIV treatment had longer median periods of follow-up in jail than those who never took HIV treatment (38 vs. 40 vs. 26 months, p <>

Read more!

Topical treatment for pre-cancerous anal cell changes safe and moderately effective

A course of treatment with topical trichloroacetic acid appears to provide a safe and effective treatment for pre-cancerous cell changes in the anus, US investigators report in a study published in the online edition of the Journal of Acquired Immune Deficiency Syndromes. The treatment was equally effective in HIV-positive and HIV-negative men. “Given its ease of use, low cost, and good safety profile, trichloroacetic acid represents a reasonable first-line therapy with carefully selected patients”, comment the investigators. Higher rates of anal cancer are seen in gay men, especially those with HIV, than in the general population. Anal intraepithelial neoplasia (AIN) is the name given to pre-cancerous changes in the anus. AIN is graded AIN I, AIN II, and AIN III according to its severity. Topical 85% trichloroacetic acid is a recommended first-line treatment for genital warts. Investigators from the University of California San Francisco Anal Neoplasia Clinic performed a retrospective study to determine the safety and effectiveness of treatment with this product for AIN. Their study involved 54 men, 35 (64%) of whom were HIV-positive. They were provided with four treatments with 85% trichloroacetic acid at intervals of one to two weeks. The treatment was administered in the clinic by healthcare staff. Treatment was considered successful if AIN II/III resolved or regressed to AIN I. It was also considered a success if AIN I resolved. Patients were followed for at regular intervals for a year after completing their treatment and were monitored for the recurrence of lesions. Of the 28 patients with confirmed AIN II/III, 32% experienced a complete resolution of their lesions, and 29% a regression of their lesions to AIN I. This provided an overall treatment response of 61%. Treatment with trichloroacetic acid led to a resolution of lesions in 73% of individuals with AIN I at baseline. Complete clearance of lesions was observed in 34% of patients with HIV and 47% of HIV-negative men, a non-significant difference. However, on a per lesion basis, the average rate of clearance was 64%. When treatment response was defined as clearance of AIN II/III or the reversion of lesions to AIN I, the response rate was 71%. Patients who cleared their lesions required a mean of two applications of the treatment. Only 5% of patients reported side-effects, the most common being pain and discomfort in the site of the treatment. HIV-positive patients with one or two lesions were significantly more likely to have a successful response to treatment than those with three or four lesions (p = 0.01). A higher CD4 cell count was also associated with a greater chance of clearance, but this did not achieve statistical significance. However, the lesions recurred in 72% of HIV-positive patients and 67% of HIV-negative men. The investigators suggest that in many cases these lesions are likely to have been new rather than the reappearance of the treated AIN. The investigators are encouraged by these results and suggest that the treatment could provide a useful first-line treatment for patients with AIN. They conclude, “larger, prospective, randomized studies are needed to determine efficacy of trichloroacetic acid for treatment of AIN in comparison with other treatment modalities and ultimately to reduce the risk of progression of AIN to invasive cancer.”

Read more!

HAART signicantly lowers risk of non-Hodgkin's lymphoma for up to ten years, regardless of nadir CD4 count

Antiretroviral therapy greatly reduces the incidence of non-Hodgkin’s lymphoma and its beneficial effect remains after ten years of treatment, according to the results of the largest, and longest, study into the effects of highly active antiretroviral therapy (HAART) on the incidence of this AIDS-defining cancer. The results were published in the January 11th edition of the journal, AIDS. Following the advent and widespread use of HAART in wealthier nations more than a decade ago, a decrease in the incidence of AIDS-related illnesses was observed, including that of non-Hodgkin’s lymphoma. However, previous studies of non-Hodgkin’s lymphoma incidence in the post-HAART era included relatively small numbers of people diagnosed with non-Hodgkin’s lymphoma following HAART initiation. Consequently, there are few data on the incidence of non-Hodgkin’s lymphoma in the HAART era and the effects of long-term HAART on incidence over time. Investigators for the Swiss HIV Cohort Study – which includes half of all people with HIV, and 68% of people with AIDS in Switzerland – analysed their database (which began in 1984 and included data until March 31st 2006) of 12,959 individuals, contributing a total of 75,222 person-years, of which 36,787 were spent on HAART. They identified a total of 429 non-Hodgkin’s lymphoma cases between 1984 and 2006 (365 from the Swiss HIV Cohort Study dataset and a further 64 from the Swiss Cantonal Cancer Registries). Of the approximately 3,870 cohort participants who developed AIDS during follow-up, non-Hodgkin’s lymphoma was the AIDS-defining illness for 201 (5.2%). They found that the highest incidence of non-Hodgkin’s lymphoma (13.6 per 1000) took place in the pre-HAART era (1993-1995). During the period, 2002-2006, the incidence declined to a low of 1.8 per 1000. The investigators found that individuals on HAART had a reduced risk (hazard ratio, HR) of non-Hodgkin’s lymphoma of 0.26 (95% CI, 0.20-0.33) compared with individuals not on HAART. Significant factors that increased the risk of non-Hodgkin’s lymphoma for individuals not on HAART included being male (HR versus women = 1.94; 95% CI, 1.43-2.61); being over 45 years of age (HR ≥ 45 versus < years =" 2.71;" users =" 1.81;" ratio =" 0.12">

Read more!

Abnormal anal cells and high-risk HPV common in HIV-positive Australians

Over two-thirds of HIV-positive patients in an Australian cohort had abnormal cells in the anus, and 84% had anal infection with strains of human papilloma virus (HPV) that are associated with a high risk of anal cancer, according to an Australian study published in the April edition of Sexually Transmitted Infections. The investigators found that infection with high risk HPV was associated with the presence of high-grade pre-cancerous cells and pre-cancerous cells of undetermined, but potentially high-grade, significance. Anal cancer is a serious condition associated with high rates of illness and death. The prevalence of anal cancer amongst gay men is thought to be similar to that amongst women before screening for cervical cancer was introduced (approximately 35 cases per 100,000). Higher rates of anal cancer have been observed in HIV-positive individuals, (but the condition is still rare in this patient group). Both anal and cervical cancer have been linked to infection with certain strains of HPV. PAP smear tests are routinely used to check for the presence of potentially cancerous cell changes in the cervix. But it is not known if such screening for anal cancer means that treatment is more likely to work and that survival rates are increased. It is however well established that localised early-stage anal cancer is more likely to respond to treatment than more advanced anal cancer, and some clinicians and treatment advocates have therefore suggested that gay men should have screens similar to PAP smears to check for abnormal cells in the anus. Studies from the US have suggested that as many as 93% of HIV-positive gay men and 14% of HIV-positive women have abnormal cells in the anus. Investigators in Melbourne and Sydney, Australia, wanted to see how many of their HIV-positive patients had abnormal anal cells and infection with high-risk HPV. The study involved 126 patients aged between 18 and 60 (median age, 45 years), most of whom (124, 98%) were gay men. All had a CD4 cell count above 300 cells/mm3, the median CD4 cell count being 545 cells/mm3. An undetectable viral load was present in two-thirds of patients. A quarter of individuals had previously been diagnosed with AIDS. A history of medical or surgical treatment of the anus was present in 25% of patients, and 18% had had anal warts removed. Anal cytology results were available for 113 patients, and 85 (67%) had cells which were to some extent abnormal. Most patients (106, 84%), had anal infection with a high-risk strain of HPV, and 79 (74%) of these individuals had abnormal anal cells. A total of 16 patients (13%) had high-grade pre-cancerous cells changes (high-grade squamous intraepithelial lesion, HGSIL), all of whom had anal infection with high-risk strains of HPV. Furthermore, 13 patients (10%) had cell changes of undetermined significance with possibly high-grade changes, and 92% of these individuals had high-risk HPV strains present. There was no association between the presence of abnormal anal cells with age, current CD4 cell count, viral load, or previous AIDS-defining illness. But previous anal treatment for warts was associated with the presence of abnormal cells (p = 0.04). Statistical analysis showed that patients with high-risk HPV were much more likely to have any abnormal anal cells (odds ratio [OR], 5.03; 95% CI: 1.45 – 17.39), and high-grade or potentially high-grade cell changes (OR, 4.22; 95% CI: 0.766 – 78.89) compared to patients who did not have high-risk HPV in the anus. Further analysis showed a statistically significant association between high-risk strains of HPV and high-grade precancerous cell changes, or potentially pre-cancerous cell changes, in the anus (p = 0.029). The investigators write, “the presence of abnormal anal cytology was significantly associated with anal infection with high-risk HPV types.” But they add, “it should be noted that high-risk HPV type anal infection was also common in people with no detected cytological abnormalities.” They suggest that screening programmes, similar to those used for cervical cancer prevention, may benefit patients with abnormal anal cell changes. However, “before such programmes are introduced, greater understanding is required of the aetiology [natural history] and role of intervention in this condition.” Patients enrolled in the study were given the opportunity to enroll into a study investigating a potential HPV-16 therapeutic vaccine.

Read more!

Non-AIDS-defining cancers now outweigh AIDS-defining cancers in US cohort

A retrospective analysis of 2566 patients in an urban HIV clinic in the US has found that rates of AIDS-defining cancers have declined dramatically since 1996. However, a wide range of other, non-AIDS-defining cancers remain more common in this HIV-positive cohort than in the general population, and now represent a large proportion of the cancers seen in this population. The results, which mirror those of many other recent studies, were reported in the February 19 issue of AIDS. "AIDS-defining" cancers are those which – in an admittedly circular definition – are defined by health authorities as constituting an AIDS diagnosis in persons with HIV. There are currently three in the United States: Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer. Many earlier studies have shown markedly decreased incidences of these AIDS-defining cancers, while many other non-AIDS-defining cancers remain more common or even appear to be on the increase among people with HIV.In this retrospective analysis, clinical records of HIV-positive patients at the Johns Hopkins University AIDS Service – a large urban clinic in Baltimore, Maryland – were analysed for diagnoses of cancer, and their outcomes. The analysis was based on the 2566 patients whose clinic medical records were available for the calendar years from 1996 to 2005, inclusive, for a total of 19,491 person-years of follow-up. This was an urban cohort with a large proportion of black, street-involved, and/or injection drug using (IDU) patients: the cohort was 68% male, 75% black, 48% heterosexual, 29% men who have sex with men (MSM) and 42% IDU, with a median age of 38; 41% were hepatitis C co-infected. The median baseline CD cell count was 281 cells/mm3 and the median viral load was 4.42 log10 copies/ml. AIDS-defining cancers Kaposi's sarcoma was diagnosed in 68 patients (standardised incidence ratio [SIR], 5600; 95% confidence interval [CI], 4400–7200), non-Hodgkin's lymphoma (NHL) in 55 (SIR, 23.1; 95% CI, 17.8–30.0), and cervical cancer in 15 (SIR, 16.6; 95% CI, 9.3–27.4) (where the standardised incidence ratios compare the observed rates to those seen in the general, HIV-negative population). Overall, rates of AIDS-defining cancers (ADCs) decreased from 12.5 cases per 1000 person-years (in 1996) to 3.5 cases per 1000 person-years (in 2005) (p<.001). This decrease was due to decreases in NHL and Kaposi's sarcoma; rates of cervical cancer remained unchanged. Non-AIDS-defining cancers A total of 115 non-AIDS-defining cancers (non-ADCs) were diagnosed in this cohort between 1996 and 2005, for an overall incidence rate of 5.9 per 1000 person-years. The annual incidence rate increased from 3.9 to 7.1 cases per 1000 person-years between 1996 and 2005 – a trend that was not quite statistically significant (p=0.13). The most commonly diagnoses were cancers of the lung (n=29; SIR, 5.5; 95% CI, 3.7–8.0), liver (n=13; SIR, 16.5; 95% CI, 8.8–28.2), anus (n=10; SIR, 39.0; 95% CI, 18.7–71.7), head and neck (n=14; SIR, 5.1; 95% CI, 2.8–8.6), and Hodgkin’s lymphoma (n=8; SIR, 9.8; 95% CI, 4.2–19.2). These rates were 5- to 39-fold higher than comparable rates in the general population. Increased rates (compared to the general population) were also seen for esophageal and bladder cancer and melanoma; risks of breast, prostate and colorectal cancers were not elevated. Other analyses In this cohort, patients with non-ADCs were more likely to be injection drug users (49% vs. 26% with ADCs, p=.001) and to have HCV co-infection (50% vs. 30%, p=.003). They also tended to be older (median 48 vs. 38 years, p<.001) and be less immunosuppressed (CD4 counts 270 vs. 60 cells/mm3, p<.001; history of opportunistic infections 57% vs. 70%, p=.033). Statistically, there was no difference in survival after diagnosis for AIDS-defining and non-AIDS-defining cancers, although the median survival time varied very widely between different types of cancer. For ADCs, older age and lower CD4 count increased the risk of mortality (adjusted hazard ratio 2.21 for age ≥ 50, 95% CI, 1.00–4.89, p=.05; hazard ratio 4.02 for CD4 count ≤ 50 cells/mm3, 95% CI, 1.75–9.26, p=.001). Neither age, race, sex, nor CD4 count were significantly associated with mortality risk for non-ADCs. However, the number of cases was too small to analyse factors affecting incidence or survival for any specific types of cancer. In conclusion, the authors note that the trends observed in this cohort "mirror trends seen nationally." Kaposi's sarcoma and non-Hodgkin's lymphoma, both of which are strongly linked to immune suppression, have become much less common, while rates of cervical cancer and many non-AIDS defining cancers have not declined. As seen in other studies, a number of non-AIDS-defining cancers including anal, lung and liver cancers, and cancers of the head and neck, were more common in this HIV-positive cohort than in the general population. These results "underscore the importance of prevention and early clinical evaluation of patients possibly symptomatic for [the more common non-AIDS-defining cancers]," particularly lung, head and neck, liver and anal cancer.

Read more!

New type of Kaposi’s sarcoma seen in HIV-negative gay men

A new variant of Kaposi’s sarcoma (KS) has been described by French skin specialists in middle-aged, HIV-negative gay men with normal immune function. The skin cancer, which is caused by HHV-8, a virus of the herpes family, is an AIDS-defining illness when it occurs in HIV-positive men. The cases seen in HIV-negative men were less aggressive and rapidly-progressing than those in people with AIDS. However they tended to be more aggressive than in the ‘classical’, originally described type of KS which is seen most often in men of Mediterranean origin, and occurred at an earlier age (mid-50s instead of late 60s). In addition the researchers found a worrying association with other cancers. One in seven of the HIV-negative KS sufferers went on to develop other cancers – in one case, another skin cancer, but in other cases cancers of the lymphatic system. This is the same proportion of patients who go on to develop other cancers as in HIV-positive KS cases. Most patients had some form of treatment – the majority topical treatment such as surgery or radiotherapy. But one in six had systemic chemotherapy. While only a minority treated with conventional anti-cancer drugs had a complete response, better results were obtained with interferon-alpha, with a complete response in two out of five patients treated and a partial response in the other three. Anecdotal cases of KS in HIV-negative people have been described in scientific literature from the late 1980s but this was the first systematic search for such patients in the post-HAART era. The researchers retrospectively studied all consecutive patients seen between 1995 and 2007 at the dermatology clinics of two Paris hospitals. During this period, approximately 300 cases of KS were seen in HIV-negative people. Of these, 28 (9%) were identified as gay or bisexual men. The researchers were unable to calculate directly whether this represented a greater prevalence of KS than in heterosexual patients, but a previous study found HHV-8 seropositivity rates of 4% in heterosexual white men attending a sexual health clinic and 24% in gay men. It is thought that HHV-8, which was only discovered in 1994, was already widespread in gay men before the advent of HIV, because prevalence figures did not increase significantly in the HIV era. HHV-8 is carried in saliva and the higher rates seen in gay men are attributed to oral sex. The average age at the onset of symptoms was 53 and at diagnosis 56 – considerably younger than the 64-72 age range for diagnosis of classical KS. The youngest person diagnosed was 35. All but two patients were white – the others were French-Caribbean and Japanese. Eleven patients had travelled in Africa, where HHV-8 is considerably more prevalent in the general population, (causing an aggressive form of KS in HIV-positive and negative people including children as young as six), and six had lived in other southern Mediterranean countries. None had immunosuppression (average CD4 count 920, range 465-1648) and only one had a history of taking immunomodulating drugs (steroids). There were no cases of the rapidly progressing type of KS involving internal organs seen in AIDS. 54% had ‘indolent’, slowly progressing lesions on one or more limbs; 32% had more aggressive, periodically inflamed lesions; while 14% had more severe disease such as widely disseminated multiple lesions or evidence of systemic disease such as swollen lymph nodes and oedema (fluid accumulation). Four patients (14%) developed other cancers after the KS diagnosis: one the skin cancer basal cell carcinoma, the other three different lymphomas; follicular lymphoma, Castleman’s disease and Burkitt lymphoma, with an average gap of five years between KS and lymphoma diagnosis. 14% of patients also had diabetes, suggesting a possible link. HHV-8 antibodies were detected in the blood of 22 of the 25 patients that were tested for them (88%). In the three negative cases antibodies were detected when more sensitive antibody tests were used on KS tissue samples. Only two of 22 patients who underwent HHV-8 DNA tests had HHV-8 virus detectable in their blood at the time of diagnosis, one with mild disease and one with severe disease. But perhaps significantly, when two out of three patients who developed lymphomas were tested, both had detectable HHV-8 viral loads at the time of these later diagnoses. In conclusion, the researchers say, they have identified a fourth type of KS to go alongside the three already known: the relatively benign ‘classical’ type seen in older Mediterranean men, the AIDS-related type, and the endemic type seen in Africa that often affects children. It appears midway in virulence between the classical and other types. Cases of KS with a similar presentation and progression pattern have also been seen in HIV-positive gay men with normal CD4 counts. While the disease was relatively benign on most cases and not life-threatening in any, KS apears to be triggered or exacerbated in HHV-8-positive people given immunomodulating drugs such as steroids, and it is of concern that in one patient that responded partially to interferon, KS later reappeared in a more aggressive form. The researchers suggest that all men who have sex with men should have their HHV-8 antibody status ascertained, especially if immunosuppressive drugs such as steroids are prescribed.

Read more!

Patients often perceive no risk if they delay attending STI clinics

Over a third of patients are declining appointments that genitourinary medicine clinics offer within the UK target time of 48 hours, a study published in the September edition of the International Journal of STD and AIDS suggests. Work commitments were the most common reason for appointments being declined. The presence of symptoms did not affect the likelihood of patients turning down an appointment within 48 hours. The investigators also found that the majority of patients declining prompt appointments did not perceive any health risks from delaying the diagnosis and treatment of sexually transmitted infections. “There are certainly a cohort of patients who have symptoms of an STI but do not see this as a risk to their health if assessment and treatment are delayed”, write the study’s authors. Prompt treatment for individuals with sexually transmitted infections helps avoid illness and discomfort in the patient and also helps prevent the onward transmission of infections. It is a UK government target that all patients seeking the services of sexual health clinics should be offered an appointment within 48 hours of requesting one. An additional target is that 95% of all individuals should be seen within 48 hours of making their appointment, although some clinicians have questioned if this is necessary. Investigators from the Department of Sexual Health at the Countess of Chester Hospital, Chester, a large genitourinary medicine clinic in north-west England, designed a study to see if patient choice to be seen within 48 hours was related to the presence of symptoms. They also wished to ascertain the perceptions of patients regarding the health consequences of untreated sexually transmitted infections. Two groups of patients were included in the study. The first comprised 110 individuals who completed questionnaires at the clinic. The second involved 138 patients who were contacted by telephone and asked questions about their decision to accept or decline an appointment within 48 hours. Records showed that all individuals contacting the clinic were offered an appointment within 48 hours. Of the individuals interviewed whilst attending the clinic, 16% recalled declining such an appointment. Work commitments were the most common reason for individuals delaying their clinic appointment (75%). A total of 37% of individuals interviewed by telephone declined an appointment within 48 hours. Symptoms were reported by 45% of those declining a prompt appointment, and work commitments were once again the most common reason (87%) for deferring attendance at the clinic. The investigators then combined the results of the two surveys. They found that individuals accepting an appointment within 48 hours were significantly more likely than the patients declining an appointment to believe that delaying their attendance at the clinic could involve health risks (41/80 vs. 9/60, p < 0.0001). “Our…data suggest that 37% of patients preferred not to accept the offer of an appointment to be seen within 48 hours. This is high”, comment the investigators. They add, “patients wish to be able to choose an appointment that suits them and are happy with this, even if it is more than 48 hours from booking.” “We should be providing information as to why being seen within 48 hours may be important”, conclude the investigators, adding “our findings represent a clear justification for increased public awareness of the dangers of sexually transmitted infections.” Although they recognise the importance of patient choice regarding the timing of appointments, the investigators stress that it is important that “their choice is an informed one.”

Read more!

Topical treatment for pre-cancerous anal cell changes safe and moderately effective

A course of treatment with topical trichloroacetic acid appears to provide a safe and effective treatment for pre-cancerous cell changes in the anus, US investigators report in a study published in the online edition of the Journal of Acquired Immune Deficiency Syndromes. The treatment was equally effective in HIV-positive and HIV-negative men. “Given its ease of use, low cost, and good safety profile, trichloroacetic acid represents a reasonable first-line therapy with carefully selected patients”, comment the investigators. Higher rates of anal cancer are seen in gay men, especially those with HIV, than in the general population. Anal intraepithelial neoplasia (AIN) is the name given to pre-cancerous changes in the anus. AIN is graded AIN I, AIN II, and AIN III according to its severity. Topical 85% trichloroacetic acid is a recommended first-line treatment for genital warts. Investigators from the University of California San Francisco Anal Neoplasia Clinic performed a retrospective study to determine the safety and effectiveness of treatment with this product for AIN. Their study involved 54 men, 35 (64%) of whom were HIV-positive. They were provided with four treatments with 85% trichloroacetic acid at intervals of one to two weeks. The treatment was administered in the clinic by healthcare staff. Treatment was considered successful if AIN II/III resolved or regressed to AIN I. It was also considered a success if AIN I resolved. Patients were followed for at regular intervals for a year after completing their treatment and were monitored for the recurrence of lesions. Of the 28 patients with confirmed AIN II/III, 32% experienced a complete resolution of their lesions, and 29% a regression of their lesions to AIN I. This provided an overall treatment response of 61%. Treatment with trichloroacetic acid led to a resolution of lesions in 73% of individuals with AIN I at baseline. Complete clearance of lesions was observed in 34% of patients with HIV and 47% of HIV-negative men, a non-significant difference. However, on a per lesion basis, the average rate of clearance was 64%. When treatment response was defined as clearance of AIN II/III or the reversion of lesions to AIN I, the response rate was 71%. Patients who cleared their lesions required a mean of two applications of the treatment. Only 5% of patients reported side-effects, the most common being pain and discomfort in the site of the treatment. HIV-positive patients with one or two lesions were significantly more likely to have a successful response to treatment than those with three or four lesions (p = 0.01). A higher CD4 cell count was also associated with a greater chance of clearance, but this did not achieve statistical significance. However, the lesions recurred in 72% of HIV-positive patients and 67% of HIV-negative men. The investigators suggest that in many cases these lesions are likely to have been new rather than the reappearance of the treated AIN. The investigators are encouraged by these results and suggest that the treatment could provide a useful first-line treatment for patients with AIN. They conclude, “larger, prospective, randomized studies are needed to determine efficacy of trichloroacetic acid for treatment of AIN in comparison with other treatment modalities and ultimately to reduce the risk of progression of AIN to invasive cancer.”

Read more!

Food insecurity increases risk of death for patients taking HIV treatment in Canada

Patients taking HIV treatment in Vancouver, Canada, who are food insecure have an increased risk of death, researchers report in the online edition of the Journal of Acquired Immune Deficiency Syndromes. The risk of death was especially high for food-insecure individuals who were of low weight. “Our findings suggest that targeted food supplementation coupled with other measures to alleviate poverty should…be a priority among urban poor HIV-infected individuals in well-resourced settings”, comment the investigators. There have been significant improvements in the health and life expectancy of HIV-positive patients since the advent of effective antiretroviral therapy. However, some groups of HIV-infected individuals, such as those from minority communities or patients with a history of drug or alcohol abuse, are less likely to access HIV treatment and care and have higher rates of illness and death. Food insecurity is defined as “limited or uncertain availability of nutritionally adequate safe foods or the inability to acquire personally acceptable foods in socially acceptable ways.” It has been associated with worse outcomes in a number of disease areas. Food insecurity has also been recognised as a factor contributing to the continued spread of HIV in resource-limited settings and to poorer outcomes amongst individuals living with HIV in such countries. Moreover, food insecurity was independently associated with a detectable viral load in HIV-positive patients in San Francisco. However, the relationship between mortality and food insecurity amongst patients with HIV in industrialised countries has never previously been examined. Therefore researchers from the British Columbia Centre for Excellence in HIV/AIDS’ Drug Treatment undertook a study involving 1119 individuals. The patients completed questionnaires assessing eight measures of food insecurity, and information was also obtained on non-accidental deaths. The investigators also assessed the relationship between food insecurity, death and body mass index, and their statistical analysis took into account a number of potentially confounding factors such as CD4 cell count, education, housing status, and HIV treatment history. Almost half (48%) of patients reported food insecurity. Women and individuals of aboriginal descent were more likely to report food insecurity, and it was also associated with younger age, lower CD4 cell count, high viral load, fewer years of HIV treatment, a history of injecting drug use, lower education, and unstable housing. Adherence was poorer amongst patients who were insecure than it was amongst patients who reported food security (62% non-adherent vs. 38%). Furthermore, the mortality rate due to non accidental causes was twice as high amongst patients with food insecurity compared to food secure individuals (22% vs. 11%). When the researchers took into account possible confounding factors, they still found that food insecure patients had a 50% increase in their risk of death (adjusted hazard ratio [AHR] = 1.51, 95% CI, 1.03-2.23). The investigators’ analysis then considered the role of low body weight. They found that after controlling for all possible confounding factors, patients who were both food insecure and underweight (BMI below 18.5 m2) were almost twice as likely to die than patients who were neither food insecure nor underweight (AHR = 1.94, 95% CI, 1.10-3.40). Finally, the researchers found that mortality rates were significantly elevated in food insecure patients who were underweight (p < 0.008) and also in food insecure patients of normal weight (p < 0 .001). “We found that HAART-treated individuals who were food insecure were significantly more likely to die of nonaccidental causes compared with individuals who were food secure”, write the investigators. They stress that there was a very high prevalence of food insecurity in their study population meaning that “the negative impacts of food insecurity on health outcomes may be experienced by a large proportion of urban poor HIV-infected individuals.” The investigators conclude, “novel interventions to alleviate food insecurity and poverty among urban poor individuals in resource-rich settings are needed to avoid clinical deterioration and excess mortality.” They therefore recommend that “clinicians caring for HIV infected individuals may consider working in multidisciplinary teams that include both case managers and nutritionists. These teams can screen individuals for food insecurity and poor nutritional status, inquire about barriers to food access, and help individuals who are food insecure identify reliable sources of good quality food”.

Read more!

Further evidence that HIV-positive men have higher rates of anal cancer

HIV-positive men are at significantly greater risk of developing anal cancer than men who do not have HIV, say US researchers writing in the Journal of Acquired Immune Deficiency Syndromes. As HIV therapy means HIV-positive people are living longer, they add, this cancer is posing an increasing problem. The incidence of anal cancer has increased in the past decade – particularly among some subgroups of the population. It is already known that HIV-positive men - and men who have sex with men - are at increased risk of anal cancer compared to the general population. Now researchers at the John Hopkins Bloomberg School of Public Health in Baltimore have compared the incidence and risk factors for anal cancer in HIV-positive and HIV-negative men who have sex with men. In the follow-up period between 1984 and 2006 there were 28 cases of anal cancer in the 6972 men studied. But the incidence was almost five times greater in HIV-positive men - with a rate of 69 cases per 100,000 patient years compared to just 14 cases per 100,000 in the HIV-negative group. The researchers also compared incidence rates in the years since effective antiretroviral treatment became available to the pre-treatment era. They found that - among HIV-positive men - the incidence of anal cancer was higher since effective HIV treatment became available – 137 cases per 100,000 person years compared to 30. It is thought this might be because improved survival is allowing enough time for pre-cancerous lesions to develop into full-blown cases of anal cancer. A further analysis of the data confirmed a previously noted result that the risk of anal cancer rose with increasing number of unprotected receptive anal sex partners among the HIV-positive men. Anal cancer – like cervical cancer – is associated with infection with the human papillomavirus (HPV). HIV treatment has reduced the risk of many HIV-associated illnesses, but studies like this suggest it does not reduce the risk of HPV-associated anal, genital and oropharyngeal cancers. Although cervical cancer is currently considered to be an AIDS-defining illness, anal cancer is not. The researchers conclude by saying that anal cancer may be preventable but the benefits of screening for it and treating it have not yet been fully evaluated. They call for further research to calculate the benefits and costs of risk reduction interventions, screening and treating pre-cancerous anal lesions in high-risk individuals such as those living with HIV.

Read more!

Incidence increasing of HIV-associated multicentric Castleman's disease, a relatively rare lymphatic cancer

Increasing numbers of cases of the relatively rare lymphatic cancer, multicentric Castleman's disease, are being diagnosed in HIV-positive individuals attending the UK’s largest HIV clinic, according to a presentation to the XVII International AIDS Conference in Mexico City earlier this month by Dr Mark Bower of London’s Chelsea and Westminster Hospital. Castleman’s disease, first described 50 years ago by Dr Benjamin Castleman, is a disorder resulting from over-activity of lymph tissue that can develop into a type of lymphoma. Although rare, it is most often seen in HIV-positive individuals as multicentric Castleman's disease (MCD) which is characterised by swollen lymph nodes, fever, fatigue, weight loss, night sweats, blood disorders and sometimes liver and spleen irregularities. Like Kaposi’s sarcoma (KS), MCD is caused by human herpesvirus-8 (HHV-8). Unlike KS, however, is it very difficult to diagnose and, as Dr Bower revealed during his presentation, MCD is neither associated with a prior AIDS diagnosis, nor are men disproportionately affected. No information exists regarding the incidence and risk factors for MCD in HIV-positive individuals, so these data from the Chelsea and Westminster cohort – which includes 10,997 patients, prospectively followed for over 56,202 patient-years between 1983 and 2007 – provide the first overview of the impact of MCD on HIV-positive people. Since MCD and KS are caused by the same virus, the investigators compared the incidence of both diseases over time. During 25 years of follow-up there were 1180 diagnoses of Kaposi's sarcoma in the Chelsea and Westminster cohort, compared to just 24 cases of multicentric Castleman's disease. This translates to a MCD incidence of 4.3 cases per 10,000 patient-years – about one-fiftieth of KS incidence. However, when incidence was examined during three time periods – the pre-highly active antiretroviral therapy (HAART) era (1983-1996); the early HAART era (1997-2001); and the current HAART era (2002-2007) – incidence of multicentric Castleman's disease was found to have risen progressively, from 0.58 cases per 10,000 patient-years in the pre-HAART era; to 2.8 cases per 10,000 patient-years in the early HAART era; to 8.3 cases per 10,000 patient-years in the current HAART era. Dr Bower conceded that, “there may be some diagnostic ascertainment bias” in the current era, since "we're more familiar with the diagnosis and more likely to make the diagnosis and search for it a bit harder." However, he pointed out, rising MCD incidence in this cohort comes in stark contrast to declining KS incidence over the same three time periods. Multivariate analysis found that unlike the risk of developing KS – which is much greater in men, and much greater with a prior AIDS diagnosis – this was not the case for multicentric Castleman's disease. “There was no gender preference for developing Castleman's disease,” said Dr Bower. The factors that were associated with an increased risk of developing multicentric Castleman's disease included:
increasing age;
non-Caucasian ethnicity – the risk was higher particularly in black African members of the cohort;
a shorter duration since HIV diagnosis; and
higher, rather than lower, nadir CD4 cell counts, unlike most HIV-related cancers – one third of MCD patients in the cohort had CD4 counts above 350 cells/mm3. In addition, the analysis found that HIV treatment appears to protect against the development of multicentric Castleman's disease. Although he said that MCD is "a diagnosis that we're going to be making more frequently", Dr Bower pointed out that “the diagnosis is very difficult to make” since clinical and pathological features of MCD overlap with a large number of other illnesses in people who are HIV-positive. Although a lymph node biopsy is the most effective way of establishing a diagnosis, data from the Chelsea and Westminster suggest that measuring HHV-8 plasma viral load may be an important diagnostic tool. In a study of 240 HIV-positive individuals, the vast majority (83%) of those with multicentric Castleman's disease had a detectable HHV-8 viral load at the time of active MCD whereas 65% of those with KS, and 97% of those with lymphoma from other causes had undetectable HHV-8 viral load (p = 0.0001). In addition, individuals with KS with detectable HHV-8 had far lower median viral loads compared with the individuals with multicentric Castleman's disease (3900 vs 41,000 copies/ml). He added that other data suggested that using the HHV-8 viral load may be a helpful marker of MCD activity, since it will fall when the disease goes into remission, and rise again when the disease relapses. However, “as yet,” said Dr Bower, “this is an insufficient assay to make the diagnosis of Castleman's disease, but it certainly seems to help push towards undertaking a biopsy.” Data published in the pre-HAART era suggested that the median survival following a diagnosis of HIV-associated multicentric Castleman's disease was 14 months. However, Dr Bower and colleagues have recently seen long-term remissions with a two-year survival rate of 95% and a five-year survival rate of 67%, following dramatic improvements in treatment that combines chemotherapy and immunotherapy. (Bower 2007) Dr Bower concluded by reiterating that the incidence of multicentric Castleman's disease appears to be rising; and that, unlike KS, the risk of MCD is not associated with the degree of immunosuppression. He added that plasma HHV-8 viral load may be used as a useful diagnostic marker, and that with an aggressive combination of chemotherapy, immunotherapy and splenectomy surgery, where necessary, a five-year survival rate of 67% can be achieved. The British HIV Association (BHIVA) has recently published guidelines in HIV Medicine on the diagnosis and management of HIV-associated malignancies that includes a section on multicentric Castleman's disease.

Read more!