Thursday, October 22, 2009

HIV-positive adolescents more likely to have poor language and writing skills

HIV-positive children and adolescents have poor language and reading skills, American researchers report in the June edition of AIDS Patient Care and STDs. The study also showed that HIV-exposed but uninfected children had lower educational attainment than expected for their age. “This study demonstrates poor verbal and reading ability among youths infected with and affected by HIV, and highlights the importance of educational interventions that address this emergent need,” comment the investigators. Thanks to effective HIV treatment, the majority of children infected with HIV by their mother are now surviving into adolescence. In New York City, where the current study was conducted, the majority of HIV-positive children and adolescents are from migrant or other minority racial/ethnic communities. There are often multiple factors that affect the educational and cognitive development of these children. These include exposure to illicit substances when in the womb, residence in areas with under-performing schools, and infrequent school attendance because of ill health. Although there is a considerable amount of research showing that infection with HIV has an adverse impact on the educational development of younger children, the data concerning older children and adolescents are limited. Therefore investigators compared the language and reading skills of 340 children and adolescents. Of these, 206 were HIV-positive, the others being HIV-exposed but uninfected. Recruitment to the study took place between 2003 and 2007. Information was also gathered on the children’s demographics, their school record, and for HIV-positive children, their CD4 cell count, viral load and use of antiretroviral therapy. The study participants were aged between nine and 16 years. The HIV-infected children had a median CD4 cell count of 572 cells/mm3. The majority (84%) were taking antiretroviral therapy, but only 34% had a viral load below 400 copies/ml. Tests showed that HIV-positive children had poorer word recognition (p = 0.008) and writing skills (p = 0.028) than the HIV-exposed children. Furthermore, the HIV-positive children were also more likely than their HIV-negative peers to have a history of special educational placement (52% vs 37%, p < p =" 0.024)" p =" 0.02)" p =" 0.018).

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Deaths in older children, teenagers with HIV set to grow in southern Africa

A growing epidemic among child and adolescent survivors of mother-to-child HIV transmission in southern Africa is emerging, highlighting the failure to recognise its development and address the clinical needs of this population, research published in the September 24th issue of AIDS shows. Although there is a high risk of death in the first year of life for infants infected perinatally, children may live with asymptomatic HIV infection for long periods, undiagnosed. According to the authors of the study, from South Africa, Zimbabwe and London’s School of Hygiene and Tropical Medicine, over one third of untreated HIV-infected children are slow progressors, with a median life expectancy of 16 years of age, whereas fast progressors die within a year. Deaths in South Africa among untreated HIV-infected children identified as slow progressors will increase from 7,000 a year in 2008 to 23,000 a year by 2030, the authors project. Provision of treatment to prevent mother-to-child transmission, they estimate, could reduce the death rate in South Africa to 8,700 a year by 2030 and in Zimbabwe to 2,800 a year by 2014. While some progress has been made to address the gap that persists in sub-Saharan Africa between those in need of antiretroviral treatment and those who receive it, the authors point out that numbers and outcomes of HIV-infected children and adolescents (defined by the World Health Organization as those between 10 and 19 years of age) remains uncertain. Most population-based HIV prevalence surveys have excluded children aged 5 to 15. However, recent surveys in Botswana, South Africa, Zimbabwe and Swaziland have included them, and have detected increasing numbers of HIV-infected children in this region seeking care. Despite the rising numbers,he authors note few HIV-related services are available to older children and adolescents. To estimate the future HIV burden among older children in two southern African countries, South Africa and Zimbabwe, illustrative of different stages of severe HIV epidemics the authors modeled population data, HIV prevalence, mother-to-child transmission and child survival data. Since there are no cohort studies of more than five years duration of children infected by their mothers the authors chose to combine available data with a meta-analysis of 38 studies in developed countries that determined survival as a function of age. The resulting data were sued to determine the proportion of fast and slow progressors in the population, after adjustment. To confirm the strength of the data the authors compared their predictions to available epidemiological data. The authors predict HIV prevalence among 10 year olds in South Africa will increase from 2.1% in 2008 to 3.3% in 2020, while in Zimbabwe a decrease from 3.2% in 2008 to 1.6% in 2020 is anticipated. The difference in predicted outcomes, say the authors, is explained by the different stages of the epidemic in South Africa and Zimbabwe. South Africa’s epidemic is approximately ten years behind Zimbabwe, where adult prevalence peaked in the late 1990s and has since declined. The authors suggest that recent recognition of the scale of the epidemic is explained in part by its slow and persistent nature in contrast to the immediacy of infant deaths. It is unknown why some children die within a relatively short time after infection and others do not. The authors suggest this is due perhaps to changes in the immune system making those infected after birth, through breastfeeding rather than during pregnancy or delivery, more likely to be slow progressors. The numbers of older (child) survivors increases for 10-20 years after having peaked in adults explaining the current high numbers. This also implies that even with scale up of PMTCT the current cohort of infected children will continue to grow. The authors note limitations of the study due to the lack of reliable age-specific cohort data from southern Africa on which to base projections, underscoring the need for better monitoring and more complete data in this population The authors stress that this population is poorly served by routine testing and care services largely due to the underestimation of the extent and nature of adolescents living with HIV in Africa. They conclude: “While awaiting more precise projections there is an urgent need to develop and rapidly implement policies and programmes aimed at providing early diagnosis, treatment and care including secondary prevention services to the expanding numbers of children and adolescents who are growing up with HIV.”

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Screening tool for HIV in children not being used effectively by health care workers

Incorrect use in routine practice of a World Health Organization (WHO)/UNICEF HIV screening tool for children at primary health care clinics in Limpopo and KwaZulu Natal provinces, South Africa, leads to the failure of life-saving interventions, Christiane Horwood and colleagues reported in a study in the September 22 2009 edition of BMC Pediatrics. Forty per cent of trained health workers failed to identify HIV in any child and not one was able to classify every child correctly for HIV. In South Africa where HIV prevalence rates among pregnant women remain at 29%, the burden of paediatric HIV disease continues to grow. Limpopo – with a mostly rural population of 5.5 million – has high rates of poverty and poor access to basic services. While KwaZulu Natal has less poverty, half of the 10-million-strong population lives in rural areas and antenatal HIV prevalence in 2006 was close to 40%. Insufficient testing and follow-up of HIV-exposed children leads to high mortality rates with over half of untreated children dying within the first two years of life. Few children who need antiretroviral treatment receive it in spite of it being free. Improved follow-up of HIV exposed children, increased early identification of children with symptomatic HIV and improved access to ART for children are urgently needed. New guidelines from WHO recommend that, where virological testing is unavailable, children should be started on antiretroviral treatment based on clinical diagnosis alone followed by quick confirmation of HIV status. WHO and UNICEF developed the Integrated Management of Childhood Illnesses (IMCI) strategy to improve child survival in resource-poor settings. Focusing on the well-being of the whole child, the aim is to reduce death, illness, disability, and to promote improved growth and development among children under five years of age. South Africa adopted these guidelines as the standard of care for children at the primary level in 1997. Multi-country evaluations of the IMCI strategy indicate, when used correctly, improved health worker performance and quality of care as well as a reduction in under-five mortality and improved nutritional status. The guidelines have been adapted to incorporate a validated HIV component (including an algorithm) to identify and manage HIV-infected (at risk for early death) and exposed (symptomatic) children. The IMCI course includes comprehensive training on this component. For effective use of the algorithm, healthcare workers are expected to ask every mother bringing a sick child to a healthcare facility whether she has been tested for HIV, so that children may be classified as HIV-exposed, and all children should be assessed for clinical symptoms suggestive of HIV. The presence of three or more symptoms should trigger further investigation and the carer should be advised of the need for the child to be tested for HIV. In this first known evaluation of the IMCI/HIV guidelines, the study was designed to show how the guidelines are used by IMCI trained health workers, the validity of the HIV algorithm when used by expert IMCI practitioners in routine practice and the burden of HIV disease among under-fives attending primary health care facilities in Limpopo and KwaZulu Natal provinces. Between May 2006 and January 2007 seventy-seven randomly selected IMCI trained health workers were observed by IMCI experts in 74 primary health care facilities in Limpopo and KwaZulu Natal provinces. All sick children between the ages of two months and five years were eligible. Consultations with a total of 1357 sick children were observed. A different IMCI expert reassessed each child to confirm correct findings. Consent for HIV testing for all children who attended was requested from parents or legal guardians. Positive rapid tests were confirmed with HIV polymerase chain reaction (PCR) tests in children under 18 months of age. HIV-positive children had CD4 counts and HIV clinical staging done. Each health worker was observed for a mean of 2.2 days and 17.7 consultations. The average age of the observed children was 19.6 months, of whom 40.7% (552) were under one year of age. A third of all consultations were observed in Limpopo and the remaining two-thirds in KwaZulu Natal. Of the 1064 children with available HIV test results, 76 tested positive giving an HIV prevalence rate of 7.1% (CI: 5.7 to 8.9%) among children in primary healthcare clinics. Of these 76, one was on antiretroviral treatment. Following CD4 counts or, if unavailable, WHO clinical staging, ART was indicated for 84% (63 of 75) of the remaining children. When compared to the HIV test results, IMCI experts skilled at using the HIV algorithm correctly identified 90.8% (69 of 76) of HIV-infected children as either suspected symptomatic HIV or HIV-exposed and therefore in need of further investigation. This shows that when used correctly the HIV algorithm is an effective screening tool and can lead to improved access to life-saving treatment for HIV infected and exposed children. In comparison, over 40% of IMCI-trained health workers failed to identify HIV in any child because of poor or incomplete use of the HIV component. And nine did not classify the disease stage of any child with HIV correctly. Even when health workers classified children with suspected symptomatic HIV, the need for testing, cotrimoxazole prophylaxis and feeding advice was only communicated to 64%, 31% and 43% of carers, respectively. The authors suggest several reasons for poor use of the algorithm:
Inadequate training
Lack of a clear understanding that the HIV algorithm is a screening tool and not a diagnostic test. IMCI training must clearly explain that most children will test negative and provide appropriate counselling messages. Even with a sensitivity of over 90% in this high-prevalence population it has a low positive predictive value (PPV) which would be lower still when used in low-prevalence settings
Poor use of the algorithm may be reflective of an overall poor use of IMCI due to: heavy workloads, lack of time for consultation, absence of clinical supervision and support
Poor application of prevention of mother-to-child transmission (PMTCT) programmes. Even though many mothers reported testing positive, few HIV-exposed children had been tested and most clinics did not test children under five. 73% of mothers had been tested for HIV, of whom 24% (221) tested positive. Of the 221 HIV-exposed children, only 35% (78) had been tested for HIV within routine services.The authors recommend the strengthening of PMTCT and linkage with IMCI as well as improved access to HIV PCR for exposed children. This may reduce the need for the algorithm to identify symptomatic HIV. However, it will remain important for children whose mothers do not disclose their status or become infected during pregnancy and breastfeeding, and in settings where virological testing is not available. The authors note that these findings show that undiagnosed HIV infection is common in primary healthcare clinics among under-five year olds and most have advanced disease. Current recommendations suggest that antiretroviral treatment is begun in children under one year of age as soon as HIV status is confirmed. They also note that their findings support the IMCI recommendation to check all children for possible HIV infection. The authors highlight the study’s strengths. The IMCI experts were all highly experienced and provided a “reliable gold standard”; observation of large numbers of children and health workers made it possible to describe performance using the health worker as the unit of analysis. Health workers had no notice of the observation and observation of large numbers over several days reduced bias. The authors note several limitations. The observer’s presence may have influenced performance and led to bias. For example, health workers may have worked out what to do during the observation. Evaluation of individual ability to identify specific signs did not take place to avoid interference during the consultation. Evaluation of the sensitivity of HIV rapid tests in children under 18 months of age remains incomplete. They did not get CD4 results for all HIV-infected children. The authors conclude that IMCI and the correct use of the current guidelines can identify HIV-infected and exposed children and provide increased and earlier access to care in South Africa to reduce under-five mortality. However, poor use of the guidelines limits its potential. The authors suggest further study to understand poor health worker performance “to provide evidence-based interventions to address poor IMCI implementation”.

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CD4 cell count below 500 increases cancer risk for patients with HIV

Maintaining a CD4 cell count above 500 cells/mm3 will protect HIV-positive patients from a range of AIDS-defining and non-AIDS-defining cancers, French investigators conclude in a paper published online on October 8th in The Lancet Oncology. The investigators analysed the rates of the seven most common cancers in people with HIV and found that CD4 cell count was the strongest risk factor for several of them. Most of the patients in the study, which included data collected between 1998 and 2006, were taking antiretroviral therapy. “Our results suggest that combination antiretroviral therapy would be most beneficial if it restores or maintains the CD4 cell count above 500 cells/mm3, thereby indicating earlier diagnosis of HIV infection and earlier treatment initiation”, comment the authors. Current guidelines recommend that HIV treatment should be started when a patient’s CD4 cell count is in the region of 350 cells/mm3. The findings of the French study will support the arguments of clinicians who believe that there will be additional survival benefits if treatment is started before a patient's CD4 cell count falls below 500 cells/mm3. Infection with HIV is associated with an increased risk of developing a number of cancers. Since effective HIV therapy became available there have been falls in the incidence of the AIDS-defining cancers Kaposi’s sarcoma and non-Hodgkin’s lymphoma, but the number of cases of several non-AIDS-defining cancers has increased. Many of these non-AIDS-defining cancers are linked to other infections, but it is unclear what role CD4 cell count, viral load and the use of antiretroviral therapy have in the development or prevention of several malignancies. Therefore investigators examined the French hospital HIV database to determine the incidence of the seven most common cancers in patients with HIV and their relationship with CD4 cell count, viral load and use of HIV treatment. These cancers were Kaposi’s sarcoma, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, lung cancer, liver cancer, cervical cancer and anal cancer. A total of 52,278 patients with 253,353 person years of follow-up were included in the analysis. HIV treatment was used by 73% of patients for the total period of follow-up between 1998 and 2006. Kaposi’s sarcoma was the most commonly diagnosed cancer (565 patients, incidence 2.32 per 100 person years). The next most common was non-Hodgkin’s lymphoma, which was diagnosed in 511 patients (incidence 2.09 per 100 person years), followed by lung cancer (207 cases, incidence 0.85 per 100 person years). There were also 149 cases of Hodgkin’s lymphoma (incidence 0.61 per 100 person years), 119 diagnoses of liver cancer (incidence 0.49 per 100 person years) and 74 cases of anal cancer (incidence 0.30 per 100 person years); cervical cancer was detected in 69 patients (incidence 0.93 per 100 person years). Most cancers developed approximately six to eight years after a patient was first diagnosed with HIV. However, both liver and anal cancer were associated with a longer duration of HIV infection, being diagnosed an average of ten years after diagnosis with HIV. Patients diagnosed with Kaposi’s sarcoma and non-Hodgkin’s lymphoma had low nadir and current CD4 cell counts (below 200 cells/mm3). Moreover, although half of the patients diagnosed with these malignancies were receiving antiretroviral therapy, they had a high viral load suggested frequent virological failure. HIV treatment was being used by two-thirds of patients diagnosed with non-AIDS-defining cancers. These patients had a median CD4 cell count of 244 cells/mm3, and median viral load was approximately 500 copies/ml. Nearly all the patients diagnosed with anal cancer were taking antiretroviral therapy. These individuals had a nadir CD4 cell count of 68 cells/mm3, had a long duration of diagnosed HIV infection, had spent an average of two years with a CD4 cell count below 200 cells/mm3, and a year with a viral load above 100,000 copies/ml. Median CD4 cell count at the time anal cancer was diagnosed was 276 cells/mm3. The investigators tested the risk factors for all seven cancers using 78 statistical models. These showed a clear relationship between CD4 cell count and the development of all the cancers with the exception of anal cancer. Indeed, the risk of these cancers was significantly increased for patients with a CD4 cell count between 350 and 499 cells/mm3 compared to patients with a CD4 cell count above 500 cells/mm3. A high viral load (above 100,000 copies/ml) was associated with an increased risk of AIDS-defining cancers, whereas the use of antiretroviral therapy, even when immunological and virologic responses were controlled for, was protective. The risk of anal cancer increased by 30% each year a patient had a CD4 cell count below 200 cells/mm3 (RR = 1.3; 95% CI, 1.2 to 1.5, p = 0.0001), and by 20% each year viral load was above 100,000 copies/ml (RR = 1.2; 95% CI, 1.1 to 1.14, p =0.005). Taking antiretroviral therapy reduced the risk of cervical cancer by 50% (RR = 0.5; 95% CI, 0.3 to 0.09, p = 0.03), and a higher CD4 cell count also significantly reduced the risk of this malignancy (p = 0.0002). “Immunodeficiency increased the risk of all the cancers that we investigated”, write the investigators, who suggest “immune deficiency would impair the ability of host cells to limit expansion of tumoral cells or viral replication”. The investigators emphasise that prompt diagnosis of HIV and the early initiation of antiretroviral therapy could cut the risk of cancer. They also suggest “access to cervical cancer screening programmes should be offered to all HIV-positive women, and cancer-specific screening programmes, such as for lung cancer and for anal cancer, need to be assessed in HIV-infected patients.”

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Wednesday, October 7, 2009

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

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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 <>

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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.”

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