Articles tagged as "Asia"

Novel specimens feasible and sensitive for Xpert® MTB/RIF diagnosis in children

Performance of Xpert® MTB/RIF and alternative specimen collection methods for the diagnosis of tuberculosis in HIV-infected children.

Marcy O, Ung V, Goyet S, Borand L, Msellati P, Tejiokem M, Nguyen Thi NL, Nacro B, Cheng S, Eyangoh S, Pham TH, Ouedraogo AS, Tarantola A, Godreuil S, Blanche S, Delacourt C, PAANTHER study group. Clin Infect Dis. 2016 Feb 7. pii: ciw036. [Epub ahead of print]

Methods: HIV-infected children aged 13 years with suspected intrathoracic tuberculosis were enrolled in 8 hospitals in Burkina Faso, Cambodia, Cameroon, and Vietnam. Gastric aspirates were taken for children aged <10 years and expectorated sputum samples were taken for children aged 10 years (standard samples); nasopharyngeal aspirate and stool were taken for all children, and a string test was performed if the child was aged 4 years (alternative samples). All samples were tested with Xpert®. The diagnostic accuracy of Xpert® for culture-confirmed tuberculosis was analyzed in intention-to-diagnose and per-protocol approaches.

Results: Of 281 children enrolled, 272 (96.8%) had ≥1 specimen tested with Xpert® (intention-to-diagnose population), and 179 (63.5%) had all samples tested with Xpert® (per-protocol population). Tuberculosis was culture-confirmed in 29/272 (10.7%) children. Intention-to-diagnose sensitivities of Xpert® performed on all, standard, and alternative samples were 79.3% (95% confidence interval [CI], 60.3-92.0), 72.4% (95% CI, 52.8-87.3), and 75.9% (95% CI, 56.5-89.7), respectively. Specificities were 97.5%. Xpert® combined on nasopharyngeal aspirate and stool had intention-to-diagnose and per-protocol sensitivities of 75.9% (95% CI, 56.5-89.7) and 75.0% (95% CI, 47.6-92.7), respectively.

Conclusions: The combination of nasopharyngeal aspirate and stool sample is a promising alternative to methods usually recommended by national programs. Xpert® performed on respiratory and stools samples enables rapid confirmation of tuberculosis diagnosis in HIV-infected children.

Abstract access  

Editor’s notes: This article reports on a prospective cohort study of HIV-positive children (≤ 13 years) with suspected intrathoracic tuberculosis in eight hospitals in Burkina Faso, Cambodia, Cameroon, and Viet Nam. Diagnosis of tuberculosis among children is challenging because it is more difficult to obtain sputum, and their sputum often has fewer bacilli, requiring more sensitive tests. In 2014, WHO recommended scaling-up the use of Xpert® MTB/RIF among children. However, any test which is dependent on obtaining a sputum specimen will be suboptimal for diagnosis of tuberculosis in children.

In this study the investigators examined the feasibility of using alternative specimens with Xpert® MTB/ RIF for the diagnosis of tuberculosis in HIV-positive children. Using an intention-to-diagnose and a per-protocol analysis, they also assessed the diagnostic accuracy of Xpert® on nasopharyngeal aspirate and stool samples, using culture-confirmed tuberculosis as the reference standard.

The authors found that the performance of Xpert® in alternative samples was comparable to that of standard samples. They found excellent feasibility of obtaining samples of nasopharyngeal aspirates and stool, and a good sensitivity of Xpert® (~76%) when using that combination of samples. The authors suggested more research to simplify the processing of the stool samples for Xpert®, which would make the combination of both samples an attractive collection method for children unable to produce sputum.

Although Xpert® produces results relatively rapidly, some testing was done retrospectively, and only half of the Xpert® results were immediately available. As many children in this study had features of severe disease, it is not surprising that clinicians often started TB treatment immediately without waiting for results. Thus in practice the Xpert® result often provided bacteriological confirmation of a clinical diagnosis for children who had already started TB treatment, although it did also lead to some TB treatment initiations.

Despite conducting this study over more than two years in eight hospitals, the final number of enrolled children with culture-confirmed tuberculosis was only 29. It would be interesting to know whether using Xpert® on alternative specimens from children had an impact on patient-important outcomes, particularly mortality, though this would have required a much larger study. Studies of Xpert® implementation among adults have found increased yield in terms of bacteriological diagnoses. However, most have not found an impact on patient-important outcomes. Several children died before all the protocol-required specimens could be obtained, emphasizing the importance of rapid and more sensitive TB diagnostic tests for severely-ill children.

Africa, Asia
Burkina Faso, Cambodia, Cameroon, Viet Nam
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Time to consider older adults on ART

Risk factors for mortality during antiretroviral therapy in older populations in resource-limited settings.

O'Brien D, Spelman T, Greig J, McMahon J, Ssonko C, Casas E, Mesic A, Du Cros P, Ford N. J Int AIDS Soc. 2016 Jan 14;19(1):20665. doi: 10.7448/IAS.19.1.20665. eCollection 2016.

Introduction: An increasing proportion of adult patients initiating antiretroviral therapy (ART) in resource-limited settings are aged >50 years. Older populations on ART appear to have heightened risk of death, but little is known about factors influencing mortality in this population.

Methods: We performed a retrospective observational multisite cohort study including all adult patients (≥15 years) initiating ART between 2003 and 2013 in programmes supported by Medecins Sans Frontieres across 12 countries in Asia, Africa and Europe. Patients were stratified into two age groups, >50 years and 15 to 50 years. A Cox proportional hazards model was used to explore factors associated with mortality.

Results: The study included 41 088 patients: 2591 (6.3%) were aged >50 years and 38 497 (93.7%) were aged 15 to 50 years. The mortality rate was significantly higher in the age group >50 years [367 (14.2%) deaths; mortality rate 7.67 deaths per 100 person-years (95% confidence interval, CI: 6.93 to 8.50)] compared to the age group 15 to 50 years [3788 (9.8%) deaths; mortality rate 4.18 deaths per 100 person-years (95% CI: 4.05 to 4.31)], p<0.0001. Higher CD4 levels at baseline were associated with significantly reduced mortality rates in the 15 to 50 age group but this association was not seen in the >50 age group. WHO Stage 4 conditions were more strongly associated with increased mortality rates in the 15 to 50 age group compared to populations >50 years. WHO Stage 3 conditions were associated with an increased mortality rate in the 15 to 50 age group but not in the >50 age group. Programme region did not affect mortality rates in the >50 age group; however being in an Asian programme was associated with a 36% reduced mortality rate in populations aged 15 to 50 years compared to being in an African programme. There was a higher overall incidence of Stage 3 WHO conditions in people >50 years (12.8/100 person-years) compared to those 15 to 50 years (8.1/100 person-years) (p<0.01). The rate of Stage 4 WHO conditions was similar (5.8/100 versus 6.1/100 respectively, p=0.52). Mortality rates on ART associated with the majority of specific WHO conditions were similar between the 15 to 50 and >50 age groups.

Conclusions: Older patients on ART in resource-limited settings have increased mortality rates, but compared to younger populations this appears to be less influenced by baseline CD4 count and WHO clinical stage. HIV treatment programmes in resource-limited settings need to consider risk factors associated with mortality on ART in older populations, which may differ to those related to younger adults.

Abstract Full-text [free] access

Editor’s notes: This article reports on a retrospective multisite cohort analysis that examined mortality rates and factors associated with mortality on ART for older individuals (> 50 years). The authors found that mortality was nearly two times greater in populations aged >50 years compared with people aged 15 to 50 years.

Contrary to other recent research, they did not find that the effect of age on mortality was stronger at lower CD4 cell counts. However, the analysis used pooled data from very diverse settings, with the great majority of patients (77%) from Asian programmes, and only 22% from Africa (and from nine different countries). This makes it difficult to tease out risk factors for mortality.

Interestingly they found that being in an Asian programme was associated with a 36% reduction in mortality (aHR: 0.64, 95%CI 0.59-0.69) among populations between 15 and 50 years compared to being in an African programme. The authors suggest that this might be due to a lower incidence of co-morbidities including opportunistic infections in Asian populations below 50 years compared to African populations.

As little is known about what it is like living with HIV for older people in resource-limited settings, the authors conclude with suggesting further social science research to address this issue. 

Africa, Asia, Europe
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Sex and drugs: poppers and HIV risk

Poppers use and risky sexual behaviors among men who have sex with men in Beijing, China.

Zhang H, Teng T, Lu H, Zhao Y, Liu H, Yin L, Sun Z, He X, Qian HZ, Ruan Y, Shao Y, Vermund SH. Drug Alcohol Depend. 2015 Dec 10. pii:S0376-8716(15)01807-4. doi:10.1016/j.drugalcdep.2015.11.037. [Epub ahead of print]

Background: Although poppers are increasingly popular among MSM in China, little is known about the patterns of poppers use. The objectives of this study were to describe the patterns of poppers use and examine its association with sexual behaviors and HIV infection among MSM in Beijing, China.

Methods: As part of a multi-component HIV intervention trial, 3588 MSM were surveyed between March 2013 and March 2014 in Beijing, China. Blood samples were collected and tested for HIV and syphilis. The questionnaire collected information about socio-demographic and behavioral characteristics. Univariate and multivariable logistic regression analyses were performed to evaluate the correlates of poppers use.

Results: Over a quarter of men (27.5%) reported having used at least one type of drugs in the past three months. Poppers were the most popular one (26.8%). Poppers use was correlated with a higher HIV prevalence [odds ratio (OR): 1.38, 95% confidence interval (CI): 1.11-1.70]. Demographic and sexual behavioral factors associated with poppers use included: younger age [adjusted OR (AOR): 1.56, 95% CI: 1.25-1.94], higher education (AOR: 1.61, 95% CI: 1.33-1.96), alcohol use (AOR: 1.32, 95% CI: 1.10-1.60), seeking male partners mainly via the internet (AOR: 1.60, 95% CI: 1.28-2.00), multiple male sex partnership (AOR: 2.22, 95% CI: 1.90-2.60), and unprotected receptive anal intercourse (AOR: 1.52, 95% CI: 1.28-1.81).

Conclusions: In this study, poppers use was positively associated with HIV infection and unprotected anal intercourse. Intervention efforts should be devoted to promote safer sex and HIV testing and counseling among MSM who use poppers.

 Abstract access   

Editor’s notes: Poppers are butyl and other nitrites that were used in the past for heart pain. They can be inhaled to facilitate anal sex. Sniffing poppers relaxes the anal sphincter muscles, making anal intercourse easier and enhancing pleasure. Numerous studies have found an association between popper use and an increased risk of acquiring HIV. This may be due to the effect of poppers in dilating capillaries and increasing blood flow to the rectum. Such a biological effect may increase the risk to the receptive partner in anal sex, further to having less autonomy in determining whether a condom is used.

This large community-based study gathered information from adult men living in Beijing, who reported sex with men in the previous 12 months. The descriptive data reported in this paper were gathered in the first phase of what is intended to be a large multi-component HIV prevention intervention trial. These data illustrate high prevalence of popper use among gay men and other men who have sex with men in Beijing. Clearly, a priority of the trial should be testing strategies to address popper use in this population. The HIV epidemic in China has evolved to one in which sexual transmission predominates, with four out of five new infections in 2011 acquired through sexual exposure. In contrast to other drugs used to enhance sexual pleasure (such as methamphetamine, ecstasy, and ketamine), poppers are widely available in China at adult stores or through the internet. In light of the finding that popper users are more likely to use the internet, it may be possible to work with the community to design programmes using internet platforms to reach men most at risk. These could aim to raise awareness and encourage changes in sex and popper use norms to reduce HIV risk and make sex safer for gay men and other men who have sex with men in Beijing.

Asia
China
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Determinants of HIV prevention costs at scale in India

What determines HIV prevention costs at scale? Evidence from the Avahan programme in India.

Lépine A, Chandrashekar S, Shetty G, Vickerman P, Bradley J, Alary M, Moses S, Group CI, Vassall A. Health Econ. 2016 Feb;25 Suppl 1:67-82. doi: 10.1002/hec.3296. Epub 2016 Jan 14.

Expanding essential health services through non-government organisations (NGOs) is a central strategy for achieving universal health coverage in many low-income and middle-income countries. Human immunodeficiency virus (HIV) prevention services for key populations are commonly delivered through NGOs and have been demonstrated to be cost-effective and of substantial global public health importance. However, funding for HIV prevention remains scarce, and there are growing calls internationally to improve the efficiency of HIV prevention programmes as a key strategy to reach global HIV targets. To date, there is limited evidence on the determinants of costs of HIV prevention delivered through NGOs; and thus, policymakers have little guidance in how best to design programmes that are both effective and efficient. We collected economic costs from the Indian Avahan initiative, the largest HIV prevention project conducted globally, during the first 4 years of its implementation. We use a fixed-effect panel estimator and a random-intercept model to investigate the determinants of average cost. We find that programme design choices such as NGO scale, the extent of community involvement, the way in which support is offered to NGOs and how clinical services are organised substantially impact average cost in a grant-based payment setting.

Abstract  Full-text [free] access

Editor’s notes: This paper was published in the journal Health Economics, as part of a supplement on methods for economic evaluation in low-income and middle-income countries. The supplement eloquently summarizes the current state of the art for economic evaluation in these countries, providing a good background for readers who are less familiar with this field.  It also reflects challenges for the design, conduct, and use of economic evaluations in these settings and highlights some of the methodological innovations arising out of these challenges. 

This contribution reflects the importance of using cost functions when conducting economic evaluations of programmes that need to be scaled up. The authors present average costs for 138 non-governmental organisations providing HIV prevention services to key populations across four years in India, as part of the Avahan project. They find that scale is an important determinant of cost, with average costs falling as scale increases. They also find that community mobilization activities can reduce costs, potentially by encouraging uptake of other services.  Further, the way in which NGOs are supported can impact on costs. 

This article presents an important methodological step towards informing better decision-making and programme design. Understanding of cost drivers can also facilitate programme monitoring and resource allocation. This is one of the first studies fully powered to analyse the determinants of costs for NGO-delivered HIV prevention services.  The authors use a wealth of cost data which are not often available to researchers working in lower and middle income countries. As noted in the foreword for this supplement, further analysis of cost functions will be essential to inform future global and national-level decision-making in these countries. This will require investment in additional large-scale cost studies globally to generate data for this type of analysis.

Asia
India
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Tuberculous meningitis: what more can we do?

Intensified antituberculosis therapy in adults with tuberculous meningitis.

Heemskerk AD, Bang ND, Mai NT, Chau TT, Phu NH, Loc PP, Chau NV, Hien TT, Dung NH, Lan NT, Lan NH, Lan NN, Phong le T, Vien NN, Hien NQ, Yen NT, Ha DT, Day JN, Caws M, Merson L, Thinh TT, Wolbers M, Thwaites GE, Farrar JJ. N Engl J Med. 2016 Jan 14;374(2):124-34. doi: 10.1056/NEJMoa1507062.

Background: Tuberculous meningitis is often lethal. Early antituberculosis treatment and adjunctive treatment with glucocorticoids improve survival, but nearly one third of patients with the condition still die. We hypothesized that intensified antituberculosis treatment would enhance the killing of intracerebral Mycobacterium tuberculosis organisms and decrease the rate of death among patients.

Methods: We performed a randomized, double-blind, placebo-controlled trial involving human immunodeficiency virus (HIV)-infected adults and HIV-uninfected adults with a clinical diagnosis of tuberculous meningitis who were admitted to one of two Vietnamese hospitals. We compared a standard, 9-month antituberculosis regimen (which included 10 mg of rifampin per kilogram of body weight per day) with an intensified regimen that included higher-dose rifampin (15 mg per kilogram per day) and levofloxacin (20 mg per kilogram per day) for the first 8 weeks of treatment. The primary outcome was death by 9 months after randomization.

Results: A total of 817 patients (349 of whom were HIV-infected) were enrolled; 409 were randomly assigned to receive the standard regimen, and 408 were assigned to receive intensified treatment. During the 9 months of follow-up, 113 patients in the intensified-treatment group and 114 patients in the standard-treatment group died (hazard ratio, 0.94; 95% confidence interval, 0.73 to 1.22; P=0.66). There was no evidence of a significant differential effect of intensified treatment in the overall population or in any of the subgroups, with the possible exception of patients infected with isoniazid-resistant M. tuberculosis. There were also no significant differences in secondary outcomes between the treatment groups. The overall number of adverse events leading to treatment interruption did not differ significantly between the treatment groups (64 events in the standard-treatment group and 95 events in the intensified-treatment group, P=0.08).

Conclusions: Intensified antituberculosis treatment was not associated with a higher rate of survival among patients with tuberculous meningitis than standard treatment.

Abstract  Full-text [free] access 

Editor’s notes: This was a well-designed and rigorously conducted clinical trial in two tertiary referral hospitals in Viet Nam. The underlying hypothesis that intensified TB treatment might improve outcomes was based on reasonable pharmacokinetic and clinical evidence. The findings are therefore disappointing and raise more questions about how to improve outcomes from TB meningitis.

In this trial, 43% of participants were HIV-positive. Two-thirds of participants were ART-naïve and the median CD4+ count was 38 cells/µL. Almost 40% of HIV-positive participants had died by nine months. Most deaths occurred in the first month. For people that were ART-naïve, two-thirds of deaths occurred before the scheduled start of ART (eight weeks). Interestingly, mortality was not affected by being on ART at enrolment, although higher CD4+ count was associated with lower mortality. Overall, the strongest predictors of mortality were rifampicin resistance and the severity of disease at enrolment.

There is a need for continued research to optimise treatment strategies for TB meningitis. Additional analyses from this trial should help to inform this research agenda. These data also clearly highlight the need to develop strategies upstream in the health system and community to ensure earlier diagnosis and treatment of both TB and HIV. 

Comorbidity, HIV Treatment
Asia
Viet Nam
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Continuous IPT: benefits in TB prevalent settings

Continuous isoniazid for the treatment of latent tuberculosis infection in people living with HIV: a systematic review and meta-analysis.

Boon SD, Matteelli A, Ford N, Getahun H. AIDS. 2016 Jan 4. [Epub ahead of print]

Objective: This systematic review was carried out to determine the effectiveness of continuous isoniazid (given for at least 36 months) for the treatment of latent tuberculosis infection (LTBI) in people living with HIV (PLHIV).

Methods: Six databases and HIV and tuberculosis (TB) conference abstract books were searched for randomized controlled trials that compared the effectiveness of continuous isoniazid treatment with 6 months of isoniazid application. Outcomes of interest were TB incidence, mortality, adverse events and risk of drug resistance. Data were pooled using fixed-effects meta-analysis.

Results: Three studies were included, from Botswana, South Africa and India. The risk of active TB was 38% lower among patients receiving continuous isoniazid compared with isoniazid regimen for 6 months [relative risk (RR) 0.62, 95% confidence interval (CI): 0.42-0.89; I = 0%], and 49% lower for those with a positive tuberculin skin test (TST) (RR 0.51, 95% CI: 0.30-0.86; I = 7%). Similarly, individuals with positive TST had a 50% lower chance of death (RR 0.50, 95% CI: 0.27-0.91; I = 3%). Two studies found no evidence of an increase in adverse events in the continuous isoniazid group, whereas a third study, that used a different definition for adverse events, found strong evidence of increase. There was no evidence of increased drug resistance when continuous isoniazid was given.

Conclusion: For PLHIV in settings with high TB and HIV prevalence and transmission, continuous isoniazid for at least 36 months is beneficial and probably outweighs the risk of increased adverse events compared with isoniazid regimen for 6 months.

Abstract access 

Editor’s notes: Isoniazid preventive therapy (IPT) reduces TB incidence among HIV-positive people. Evidence has accumulated from settings where TB is prevalent that the protective effect of a standard six-month course of isoniazid wanes after treatment stops. This may be because of reinfection with rapid progression to TB disease. However, in high transmission settings, where the bacillary burden of latent infection could be higher, six months of isoniazid may be insufficient to “cure” latent tuberculosis infection, and reactivation of residual latent infection may also contribute to TB disease after IPT is discontinued. 

This meta-analysis puts together data from three studies that compared a longer duration of IPT to the standard six-month course. Continuous versus a six-month course of IPT reduced TB incidence. Consistent with other studies, this benefit was clear in people with a positive tuberculin skin test (TST) at baseline but smaller and not significant in people with a negative TST. This meta-analysis also found a reduction in mortality among people with a positive TST receiving continuous IPT, primarily based on data from the study in Botswana. This is notable because most previous trials of IPT versus control have not demonstrated a mortality benefit. Most trials of short-course IPT were undertaken in the pre-antiretroviral therapy (ART) era, when all-cause mortality was very high. In the Botswana study, ART was available and will have reduced HIV-associated mortality among all participants, which may have allowed a difference in TB-specific mortality to become evident.

Adverse events were very similar between the continuous versus short course IPT groups in the studies from Botswana and India. However, in the South African study, adverse events were more common in the continuous IPT group, as were temporary or permanent discontinuations due to adverse events. Abnormal liver function tests were particularly common, but it is not clear how many of these were symptomatic and thus would be detected in a programme where liver function is not routinely monitored.

These data support WHO recommendations for continuous IPT for HIV-positive people in settings where TB transmission is common. What is not clear is how to define settings where TB transmission is common enough for this recommendation to be applied. 

Africa, Asia
Botswana, India, South Africa
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Current dosages for treatment of TB in children living with HIV may be sub-optimal

Low serum concentrations of rifampicin and pyrazinamide associated with poor treatment outcomes in children with tuberculosis related to HIV status.

Ramachandran G, Kumar AK, Kannan T, Bhavani PK, Kumar RS, Gangadevi NP, Banurekha VV, Sudha V, Venkatesh S, Ravichandran N, Kalpana S, Mathevan G, Sanjeeva GN, Agarwal D, Swaminathan S. Pediatr Infect Dis J. 2016 Jan 27. [Epub ahead of print]

Objectives: To compare the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) between HIV-infected and uninfected children with TB and correlate it with TB treatment outcome.

Methods: HIV-uninfected (n = 84) and HIV-infected (n = 77) children with TB receiving standard thrice weekly treatment, were recruited from six hospitals in India. Semi-intensive pharmacokinetic sampling was performed during intensive phase of TB treatment after directly observed administration of drugs. Drug concentrations were measured by high performance liquid chromatography (HPLC). INH acetylator status was determined and nutritional assessment was done. Children were followed up and treatment outcomes noted.

Results: Children with HIV & TB had significantly lower RMP peak concentration (Cmax) (2.6 vs. 5.1µg/ml; p<0.001) and exposure (AUC0-8) (10.4 vs. 23.4 µg/ml.h; p<0.001) than those with TB. Among HIV-infected children, a significantly higher proportion had stunting (77% vs 29%; p < 0.001) and underweight (73% vs 38%; p < 0.001) compared to children with TB. Combining both groups, RMP Cmax (p = 0.001; AOR = 1.437; 95% CI: 1.157 - 1.784) and PZA Cmax (p = 0.027; AOR = 1.041; 95% CI: 1.005 - 1.079) significantly influenced treatment outcome.

Conclusions: HIV infection was associated with lower Cmax of RMP and INH and AUC0-8 of RMP. Over 90% of children in both groups had sub-therapeutic RMP Cmax. Cmax of RMP and PZA significantly influenced TB treatment outcome in children with TB. The findings have important clinical implications and suggest the need to increase anti-TB drug doses in children with HIV & TB.

Abstract access 

Editor’s notes: Determinants of outcomes in childhood TB are relatively understudied compared to outcomes among adults. The authors have conducted a detailed pharmacokinetic study in Indian children to examine the association of HIV and anthropometric indices with the peak concentrations of rifampicin (RMP), isoniazid (INH) and pyrazinamide PZA). Despite the small sample size they demonstrated that HIV-positive children fared worse in terms of achieving therapeutic levels of INH and RMP, but also that only 10% of all children achieved therapeutic levels of RMP, irrespective of HIV status and malnutrition. Similar investigations of RMP pharmacokinetics in other very recent studies (Arya et al. 2015 IJTLD, Bekker et al. 2015 Antimicrob Agents Chemother) found overall sub-therapeutic levels and also called, as the authors do, for a review of paediatric dosages in TB programmes.  Kwara et al. (2015 J Pediatric Infect Dis Soc) also observed the association of levels with HIV.

The data seem to provide scientific consensus that, assuming the recommended therapeutic serum levels are appropriate, under the current WHO TB treatment guidelines; children and infants are not receiving optimal chemotherapy for TB. The data suggest that dosages should be reviewed and that particularly in settings where a high proportion of children treated for TB are HIV-positive, that HIV-positive children may require further alterations to the schedules to ensure adequate levels for treatment success. 

Comorbidity
Asia
India
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TB still responsible for large proportion of admissions and in-patient deaths among people living with HIV

TB as a cause of hospitalization and in-hospital mortality among people living with HIV worldwide: a systematic review and meta-analysis.

Ford N, Matteelli A, Shubber Z, Hermans S, Meintjes G, Grinsztejn B, Waldrop G, Kranzer K, Doherty M, Getahun H. J Int AIDS Soc. 2016 Jan 12;19(1):20714. doi: 10.7448/IAS.19.1.20714. eCollection 2016.

Introduction: Despite significant progress in improving access to antiretroviral therapy over the past decade, substantial numbers of people living with HIV (PLHIV) in all regions continue to experience severe illness and require hospitalization. We undertook a global review assessing the proportion of hospitalizations and in-hospital deaths because of tuberculosis (TB) in PLHIV.

Methods: Seven databases were searched to identify studies reporting causes of hospitalizations among PLHIV from 1 January 2007 to 31 January 2015 irrespective of age, geographical region or language. The proportion of hospitalizations and in-hospital mortality attributable to TB was estimated using random effects meta-analysis.

Results: From an initial screen of 9049 records, 66 studies were identified, providing data on 35 845 adults and 2792 children across 42 countries. Overall, 17.7% (95% CI 16.0 to 20.2%) of all adult hospitalizations were because of TB, making it the leading cause of hospitalization overall; the proportion of adult hospitalizations because of TB exceeded 10% in all regions except the European region. Of all paediatric hospitalizations, 10.8% (95% CI 7.6 to 13.9%) were because of TB. There was insufficient data among children for analysis by region. In-hospital mortality attributable to TB was 24.9% (95% CI 19.0 to 30.8%) among adults and 30.1% (95% CI 11.2 to 48.9%) among children.

Discussion: TB remains a leading cause of hospitalization and in-hospital death among adults and children living with HIV worldwide.

Abstract  Full-text [free] access

Editor’s notes: The last 30 years have seen radical improvements in outcomes for many people living with HIV. This study reminds us that in some parts of the world HIV-associated infections, tuberculosis (TB) in particular, still have a devastating effect on thousands of lives.

The importance of TB is widely recognised. WHO aim to reduce deaths due to TB by 75% over the next 10 years.  The question remains: do we really know how many people die due to TB?  Death certification has repeatedly been shown to be unreliable, particularly in the parts of the world where TB is most prevalent. Verbal autopsy is used to estimate cause of death in areas with poor notification systems, but poorly differentiates deaths due to TB and other HIV-associated conditions. Similar challenges are faced when counting and classifying morbidity and hospitalisations. Data are sparse, and determining the cause of an admission is not straightforward, even with access to well-maintained hospital records.  

This review, a sub-analysis of data from a broader study of HIV-associated hospital admissions, is by far the largest of its kind. The authors have been rigorous, given the heterogeneity of the studies included, and their findings are sobering. Among adults living with HIV, in all areas except Europe and South America, TB was the cause of 20-33% of admissions, and some 30% of adults and 45% of children who were admitted with TB were thought to have died from it. These findings are limited by the fact that not all reviewed studies reported on mortality and very few stated how causes of death were assigned.

This paper raises more questions than it answers, but they are important questions.  We are left in no doubt that TB is a major contributor to global morbidity and mortality in HIV-positive people, but we need to look closely at how we count and classify ‘TB deaths’ and ‘TB-associated admissions’. The recent systematic review of autopsy studies cited by the authors also found that almost half the TB seen at autopsy was not diagnosed before death. Global autopsy rates are in decline. Without access to more accurate data, how will we know if we’re winning or losing in our efforts to end TB deaths?

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How gender norms and power may impact on the acceptability, access and adherence to microbicides

Optimizing HIV prevention for women: a review of evidence from microbicide studies and considerations for gender-sensitive microbicide introduction.

Doggett EG, Lanham M, Wilcher R, Gafos M, Karim QA, Heise L. J Int AIDS Soc. 2015 Dec 21;18(1):20536. doi: 10.7448/IAS.18.1.20536. eCollection 2015.

Introduction: Microbicides were conceptualized as a product that could give women increased agency over HIV prevention. However, gender-related norms and inequalities that place women and girls at risk of acquiring HIV are also likely to affect their ability to use microbicides. Understanding how gendered norms and inequalities may pose obstacles to women's microbicide use is important to inform product design, microbicide trial implementation and eventually microbicide and other antiretroviral-based prevention programmes. We reviewed published vaginal microbicide studies to identify gender-related factors that are likely to affect microbicide acceptability, access and adherence. We make recommendations on product design, trial implementation, positioning, marketing and delivery of microbicides in a way that takes into account the gender-related norms and inequalities identified in the review.

Methods: We conducted PubMed searches for microbicide studies published in journals between 2000 and 2013. Search terms included trial names (e.g. "MDP301"), microbicide product names (e.g. "BufferGel"), researchers' names (e.g. "van der Straten") and other relevant terms (e.g. "microbicide"). We included microbicide clinical trials; surrogate studies in which a vaginal gel, ring or diaphragm was used without an active ingredient; and hypothetical studies in which no product was used. Social and behavioural studies implemented in conjunction with clinical trials and surrogate studies were also included. Although we recognize the importance of rectal microbicides to women, we did not include studies of rectal microbicides, as most of them focused on men who have sex with men. Using a standardized review template, three reviewers read the articles and looked for gender-related findings in key domains (e.g. product acceptability, sexual pleasure, partner communication, microbicide access and adherence).

Results and discussion: The gendered norms, roles and relations that will likely affect women's ability to access and use microbicides are related to two broad categories: norms regulating women's and men's sexuality and power dynamics within intimate relationships. Though norms about women's and men's sexuality vary among cultural contexts, women's sexual behaviour and pleasure are typically less socially acceptable and more restricted than men's. These norms drive the need for woman-initiated HIV prevention, but also have implications for microbicide acceptability and how they are likely to be used by women of different ages and relationship types. Women's limited power to negotiate the circumstances of their intimate relationships and sex lives will impact their ability to access and use microbicides. Men's role in women's effective microbicide use can range from opposition to non-interference to active support.

Conclusions: Identifying an effective microbicide that women can use consistently is vital to the future of HIV prevention for women. Once such a microbicide is identified and licensed, positioning, marketing and delivering microbicides in a way that takes into account the gendered norms and inequalities we have identified would help maximize access and adherence. It also has the potential to improve communication about sexuality, strengthen relationships between women and men and increase women's agency over their bodies and their health.

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Editor’s notes: This paper presents a review of the evidence of microbicides research to understand gender-associated factors that could impact on acceptability, access and adherence. These gender norms include women and men’s sexual norms and power differentials in intimate partner relationships. This review included studies conducted between 2000 and 2013 and thus only includes papers on hypothetical research and clinical trials. While the studies were conducted in a variety of contexts the authors found a number of similar norms and power differentials.

In relation to sexual norms, the review revealed findings on sexual risk, sexual pleasure, and sexual preferences. In terms of sexual risk there were differing opinions across the studies of which women were most likely to need microbicides. Some studies suggested that microbicides should be focused on women in steady partnerships where condom negotiation is difficult, while others suggested focusing on key populations such as sex workers. Across many studies the potential for promoting sexual pleasure for both women and men emerged as an advantage of microbicides, and had an impact on acceptability. However, many of the studies highlighted how men’s sexual pleasure takes precedence. In relation to sexual preferences, the much touted idea that men prefer ‘dry’ or ‘tight’ sex was challenged by some of the studies, which found that the lubricating effect of the gel was acceptable.

The review also uncovered issues associated to power inequalities in intimate partner relationships, including power to control time of sex, male partner engagement and communication, and intimate-partner violence. Women reported in many studies their lack of power to control the timing of sex and this is seen as likely to impact on their ability to use coitally-dependant microbicides. However, there is some evidence that men supported women’s use of the gel, although this depended on the type of relationship. While microbicides have been promoted as products that women can use without a partner’s knowledge the review illustrated that women do prefer to communicate with their partners about their use and there is evidence of joint-decision making. Further, there was evidence of women experiencing intimate partner violence in relation to trial participation. There is also some evidence that women were less likely to discuss or use microbicides in violent relationships.

This highly comprehensive review concludes that while microbicides will not empower women they do have the potential to enhance women’s agency in relation to their health and sexuality and may improve communication in their relationships. However, the authors conclude that gender norms and power differentials may impact on acceptability, access and adherence.

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Why get tested for HIV in Russia?

Motivators and barriers to HIV testing among street-based female sex workers in St. Petersburg, Russia.

King EJ, Maman S, Dudina VI, Moracco KE, Bowling JM. Glob Public Health. 2015 Dec 28:1-16. [Epub ahead of print]

Female sex workers are particularly susceptible to HIV-infection in Russia. However, a dearth of information exists on their utilisation of HIV services. A mixed-methods, cross-sectional study was conducted to examine motivators and barriers to HIV testing among street-based sex workers in St. Petersburg, Russia. The health belief model was the theoretical framework for the study. Twenty-nine sex workers participated in in-depth interviews, and 139 sex workers completed interviewer-administered surveys between February and September 2009. Barriers to getting an HIV test were fear of learning the results, worrying that other people would think they were sick, and the distance needed to travel to obtain services. Motivators for getting tested were protecting others from infection, wanting to know one's status and getting treatment if diagnosed. Logistic regression analysis demonstrated that knowing people living with HIV [aOR = 6.75, 95% CI (1.11, 41.10)] and length of time since start of injection drug use [aOR = 0.30, 95% CI (0.09, 0.97)] were significantly associated with recently getting tested. These results are important to consider when developing public health interventions to help female sex workers in Russia learn their HIV status and get linked to care and treatment services if needed.

Abstract access 

Editor’s notes: This paper summarises findings from a mixed-method study among a sample of female sex workers in St Petersburg, Russian Federation, the majority of whom also inject drugs. This is an important study, allowing the voices of a highly marginalised group to be heard and highlighting barriers and facilitators to HIV testing. Improving access to testing among this population is particularly important given the increased risk of HIV infection that they face. They are susceptible to HIV infection through both sexual and injecting transmission routes. The paper raises some important points such as the widespread misunderstanding about the severity of HIV in the absence of symptoms. HIV was not perceived to be a major problem among the population; there were more immediate problems associated with drug use and sex work. The necessity to travel for testing was seen as a barrier to HIV testing. For a population with multiple and complex health needs this is an acute problem given the vertical structure of the Russian health system. There is a lack of integration across sexual health, drug dependency and HIV and other infectious disease treatment services necessary for this population.  Many other structural barriers were reported to testing including  fear of being registered as having HIV, fear of stigma from friends and health care workers, fear of the unknown associated with infection and disease progression and uncertainty about availability of HIV treatment.  Concerns about treatment availability are particularly relevant since people who inject drugs are often denied HIV treatment in the Russian Federation while they continue to use drugs. This point is important in understanding the context in which HIV testing is accessed. Further discussion on what real benefits knowing your status brings weighed up against the disadvantages of knowing, warrants further discussion in the paper. We know that there is limited and often interrupted HIV treatment available and few ancillary services (such as opioid substitution therapy) to support maintenance of treatment.  We also know that there is much stigma associated with being HIV positive. People living with HIV experience frequent problems with employment and concerns about having children taken into care. All these problems are compounded if you use drugs or sell sex. In this context, the benefits of knowing your status is questionable and is bound to influence uptake of testing.

Asia, Europe
Russian Federation
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