Articles tagged as "Health systems and services"

Worms and HIV – time to end the debate?

Effect of Wuchereria bancrofti infection on HIV incidence in southwest Tanzania: a prospective cohort study.

Kroidl I, Saathoff E, Maganga L, Makunde WH, Hoerauf A, Geldmacher C, Clowes P, Maboko L, Hoelscher M. Lancet. 2016 Oct 15;388(10054):1912-1920. doi: 10.1016/S0140-6736(16)31252-1. Epub 2016 Aug 3.

Background: The past decades have seen an ongoing controversial debate about whether the immune activation induced by helminths has an effect on the susceptibility of individuals to HIV. In view of this, we assessed the effect of lymphatic filariasis, a chronic helminth disease elicited by Wuchereria bancrofti, on HIV incidence in southwest Tanzania.

Methods: In this population-based cohort study, we enrolled a geographically stratified randomly chosen sample of about 10% of the households in nine distinct sites in southwest Tanzania. All household members present were followed up and tested for HIV and circulating filarial antigen, an indicator of W bancrofti adult worm burden. Our main outcome of interest was HIV incidence in participants with or without lymphatic filariasis.

Findings: Between May 29, 2006, and June 16, 2011, we enrolled 4283 households with roughly      18 000 participants. Of these, 2699 individuals from Kyela district participated in at least one round of the EMINI study. In the 1055 initially HIV-negative adolescents and adults with clearly defined lymphatic filariasis status, 32 new HIV infections were observed in 2626 person-years. HIV incidence in lymphatic filariasis-positive participants (1.91 cases per 100 person-years) was significantly higher than the incidence in lymphatic filariasis-negative participants (0.80 cases per 100 person-years). The age-adjusted and sex-adjusted incidence rate ratio was 2.17 (95% CI 1.08-4.37, p=0.0300). Lymphatic filariasis status remained an independent and significantly relevant risk factor for HIV infection when controlled for other known risk factors such as sexual behaviour and socioeconomic factors.

Interpretation: To our knowledge, this is the first prospective study demonstrating a significantly increased risk of acquiring HIV for lymphatic filariasis-infected individuals. Immunological studies and interventional treatment studies that eliminate the adult worms and not only the microfilariae are needed to follow up on the results presented.

Abstract access    

Editor’s notes: The interest in the link between helminth infections and HIV is based on our understanding of how helminth infections affect the human immune system. One core hypothesis has been that the shift to a predominantly T-helper type 2 (Th2) immune response associated with helminth infection might increase the risk of HIV acquisition. Until now, there has been no compelling evidence to support this. Observational studies looking at co-prevalence of HIV and filarial infection have not consistently illustrated an association between filarial infection and prevalent HIV infection. This relatively large population-based cohort study allowed a different approach, exploring the association between helminth infection and incident HIV infection over an average of three years follow-up. The presence of circulating filarial antigens doubled the risk of HIV acquisition.

So do the findings of this study end the debate? Perhaps not. The analysis did not account for the presence or absence of other helminth infections around the time of HIV acquisition. Also, although the analysis controlled for some socio-economic and behavioural factors known to be associated with HIV acquisition, this was incomplete so there is the possibility of residual confounding.

The findings from this study have led to renewed calls for clinical trials to evaluate the effect of antihelminthic treatment on HIV acquisition, but it may be too late. Elimination of neglected tropical diseases (including filariasis) is a global health priority in its own right, as is scale-up of combination HIV prevention strategies, including universal test and treat and pre-exposure prophylaxis. Clinical trials might therefore require unfeasibly large sample sizes to demonstrate an independent effect of antihelminthic treatment.

Africa
United Republic of Tanzania
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It’s hard to tell: healthcare workers experiences of telling children of their HIV positive status.

Experiences with disclosure of HIV-positive status to the infected child: perspectives of healthcare providers in Dar es Salaam, Tanzania.

Sariah A, Rugemalila J, Somba M, Minja A, Makuchilo M, Tarimo E, Urassa D, Siril H. BMC Public Health. 2016 Oct 13;16(1):1083.

Background: The specific age to which an HIV infected child can be disclosed to is stipulated to begin between ages 4 and 6 years. It has also been documented that before disclosure of HIV positive status to the infected child. Health care providers should consider children's cognitive-developmental ability. However, observation and situation analysis show that, health care providers still feel uncomfortable disclosing the HIV positive status to the infected child. The aim of the study was to explore healthcare providers' experiences in disclosure of HIV-positive status to the infected child.

Methods: A qualitative study involving 20 health care providers who attend HIV-positive children was conducted in September, 2014 in Dar es Salaam, Tanzania. Participants were selected from ten HIV care and treatment clinics (CTC) by purposive sampling. An interview guide, translated into participants' national language (Kiswahili) was used during in-depth interviews. Sampling followed the principle of data saturation. The interviews focused on perspectives of health-care providers regarding their experience with paediatric HIV disclosure. Data from in-depth interviews were transcribed into text; data analysis followed qualitative content analysis.

Results: The results show how complex the process of disclosure to children living with HIV can be to healthcare providers. Confusion was noted among healthcare providers about their role and responsibility in the process of disclosing to the HIV infected child. This was reported to be largely due to unclear guidelines and lack of standardized training in paediatric HIV disclosure. Furthermore, healthcare providers were concerned about parental hesitancy to disclose early to the child due to lack of disclosure skills and fear of stigma. In order to improve the disclosure process in HIV infected children, healthcare providers recommended further standardized training on paediatric HIV disclosure with more emphasis on practical skills and inclusion of disclosure content that is age appropriate for children with HIV.

Discussion: The disclosure process was found to be a complex process. Perspectives regarding disclosure in children infected with HIV varied among healthcare providers in terms of their role in the process, clear national guidelines and appropriate standardized training for paediatric disclosure. Consistent with other studies, healthcare providers reported difficulties during disclosure because parents /guardians largely fear blame, social stigma, child's negative emotional reaction when disclosed to and have concerns about the child being too young and immature to understand the HIV condition.

Conclusions: In order to prevent inconsistencies during the disclosure process, it is important to have in place clear guidelines and standardized paediatric HIV disclosure training for healthcare providers. This would help improve their skills in paediatric disclosure, leading to positive health outcomes for children infected with HIV.

Abstract  Full-text [free] access 

Editor’s notes: This valuable paper explores the experiences of healthcare providers who are disclosing to children and young people living with HIV. It focusses on a clinical setting in a district of Dar es Salaam in the United Republic of Tanzania. The authors examine factors that hinder and facilitate the process of disclosing to children and young people living with HIV through interviews with healthcare workers. Disclosure is understood to be pivotal in supporting children and young people’s adaptation to the realities of living with HIV and in managing their treatment and care effectively. While this topic has been the subject of much policy and research attention, this paper presents valuable insights into how disclosure is practised in reality. The authors point to the gap between what is in the guidelines and healthcare workers’ ability to deliver these principles within the context of the clinic. They note that disclosure is often with parental resistance and/ or concern. Another significant feature hindering healthcare workers’ ability to follow the disclosure guidelines was their limited training on disclosure, as well as in some cases their limited awareness of the guidelines. The authors present a stark picture of the distance between what ‘should’ be being done and what ‘is’ being done. The primary conclusion the authors draw is the significant need for improved training for healthcare workers. The provision of such training across clinics would enable healthcare workers to respond to the various dynamics. For example, parental reticence and lack of support, which currently result in disclosure being delayed or being done ineffectively.  

Africa
United Republic of Tanzania
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Standard methods underestimate the effect of HIV on fertility

The effects of HIV on fertility by infection duration: evidence from African population cohorts before ART availability: fertility by duration of HIV infection.

Marston M, Nakiyingi-Miiro J, Kusemererwa S, Urassa M, Michael D, Nyamukapa C, Gregson S, Zaba B, Eaton JW. AIDS. 2016 Oct 20. [Epub ahead of print]

Objectives: To estimate the relationship between HIV natural history and fertility by duration of infection in East and Southern Africa before the availability of antiretroviral therapy, and assess potential biases in estimates of age-specific sub-fertility when using retrospective birth histories in cross-sectional studies.

Design: Pooled analysis of prospective population-based HIV cohort studies in Masaka (Uganda) Kisesa (Tanzania), and Manicaland (Zimbabwe).

Methods: Women aged 15-49 who had ever tested for HIV were included. Analyses were censored at antiretroviral treatment roll out. Fertility rate ratios were calculated to see the relationship of duration of HIV infection on fertility, adjusting for background characteristics. Survivorship and misclassification biases on age-specific subfertility estimates from cross-sectional surveys were estimated by reclassifying person time from the cohort data to simulate cross-sectional surveys and comparing fertility rate ratios to true cohort results.

Results: HIV negative and positive women contributed 15 440 births and 86 320 person years; and 1236 births and 11 240 thousand person years respectively to the final dataset. Adjusting for age, study site and calendar year, each additional year since HIV sero conversion was associated with a 0.02 (95%CI 0.01-0.03) relative decrease in fertility for HIV-positive women. Survivorship and misclassification biases in simulated retrospective birth histories resulted in modest underestimates of sub-fertility by 2-5% for age groups 20-39y.

Conclusion: Longer duration of infection is associated with greater relative fertility reduction for HIV-positive women. This should be considered when creating estimates for HIV prevalence among pregnant women and PMTCT need over the course of the HIV epidemic and ART scale-up.

Abstract access 

Editor’s notes: HIV prevalence among antenatal clinic attenders is used to help estimate population HIV prevalence. It is known that figures must be adjusted upwards to reflect the fact HIV reduces fertility, especially in older women. However, older women are also likely to have been living with HIV for longer. The authors investigated whether length of infection changes the effect of HIV on fertility. Using three prospective longitudinal cohorts, they found that time since seroconversion was associated with reduced fertility, even after adjusting for age and age at seroconversion. This result is important because as the epidemic matures and the majority of women living with HIV are not recently infected, the effect of HIV on suppressing fertility will increase. This will cause measurements of HIV prevalence in pregnancy to underestimate the true population prevalence even if they adjust for age. Conversely, women who have been living with HIV for longer are more likely to be taking ART, which increases fertility relative to women who have been diagnosed more recently. Therefore, within an age-group, pregnancy data is likely to overestimate the proportion of HIV positive women on ART. The usual way to measure the age-specific effects of HIV on fertility is to compare the three-year reported fertility of women living with HIV, and women without HIV in a cross-sectional survey. The authors used longitudinal data to simulate a survey and showed that surveys slightly underestimate the size of the fertility effect, for two reasons. Firstly, if women acquire HIV during the three years any pregnancies before infection are misattributed to HIV. Secondly, there is excess mortality of HIV positive women with low fertility who therefore do not appear in the survey.

The reasons for the age-dependent effect of HIV on fertility are both biological and social (older women living with HIV are more likely to be widowed or divorced) and the relationship is not fixed over time. It shifts according to demographic factors, the stage of the epidemic and, availability of treatment. Assumptions must be continually tested as the epidemic evolves. 

Epidemiology
Africa
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Treating depression and boosting adherence together

Cognitive behavioural therapy for adherence and depression in patients with HIV: a three-arm randomised controlled trial.

Safren SA, Bedoya CA, O'Cleirigh C, Biello KB, Pinkston MM, Stein MD, Traeger L, Kojic E, Robbins GK, Lerner JA, Herman DS, Mimiaga MJ, Mayer KH. Lancet HIV. 2016 Nov;3(11):e529-e538. pii: S2352-3018(16)30053-4. doi: 10.1016/S2352-3018(16)30053-4. [Epub 2016 Sep 19]

Background: Depression is highly prevalent in people with HIV and has consistently been associated with poor antiretroviral therapy (ART) adherence. Integrating cognitive behavioural therapy (CBT) for depression with adherence counselling using the Life-Steps approach (CBT-AD) has an emerging evidence base. The aim of this study was to test the efficacy of CBT-AD.

Methods: In this three-arm randomised controlled trial in HIV-positive adults with depression, we compared CBT-AD with information and supportive psychotherapy plus adherence counselling using the Life-Steps approach (ISP-AD), and with enhanced treatment as usual (ETAU) including Life-Steps adherence counselling only. Participants were recruited from three sites in New England, USA (two hospital settings and one community health centre). Patients were randomly assigned (2:2:1) to receive CBT-AD (one Life-Steps session plus 11 weekly integrated sessions lasting up to 1 h each), ISP-AD (one Life-Steps session plus 11 weekly integrated sessions lasting up to 1 h each), or ETAU (one Life-Steps session and five assessment visits roughly every 2 weeks), randomisation was done with allocation software, in pairs, and stratified by three variables: study site, whether or not participants had been prescribed antidepressant medication, and whether or not participants had a history of injection drug use. The primary outcome was ART adherence at the end of treatment (4 month assessment) assessed via electronic pill caps (Medication Event Monitoring System [MEMS]) with correction for pocketed doses, analysed by intention to treat.

Findings: Patients were recruited from Feb 26, 2009, to June 21, 2012. Patients who were assigned to CBT-AD (94 randomly assigned, 83 completed assessment) had greater improvements in adherence (estimated difference 1.00 percentage point per visit, 95% CI 0.34 to 1.66, p=0.003) and depression (Center for Epidemiological Studies depression [CESD] score estimated difference -0.41, -0.66 to -0.16, p=0.001; Montgomery-Asberg depression rating scale [MADRS] score -4.69, -8.09 to -1.28, p=0.007; clinical global impression [CGI] score -0.66, -1.11 to -0.21, p=0.005) than did patients who had ETAU (49 assigned, 46 completed assessment) after treatment (4 months). No significant differences in adherence were noted between CBT-AD and ISP-AD (97 assigned, 87 completed assessment). No study-related adverse events were reported.

Interpretation: Integrating evidenced-based treatment for depression with evidenced-based adherence counselling is helpful for individuals living with HIV/AIDS and depression. Future efforts should examine how to best disseminate effective psychosocial depression treatments such as CBT-AD to people living with HIV/AIDS and examine the cost-effectiveness of such approaches.

Abstract access  

Editor’s notes: Clinical depression is highly prevalent in people living with HIV, and common symptoms of depression (such as poor attention and negative thinking) can lead to poor adherence to ART. There is an emerging evidence base that integrating cognitive behaviour therapy (CBT) for adherence with CBT for depression may improve ART adherence, but this is based on relatively few, small, studies. This paper presents results of a full-scale three-arm efficacy trial to evaluate a CBT-based programme on HIV outcomes among people living with HIV with comorbid depression (CBT-AD) compared with a time-matched information and supportive psychotherapy activity with adherence counselling (ISP-AD), and enhanced treatment as usual.  The CBT-AD programme is based on the Life-Steps adherence counselling programme - a problem-solving approach to help people identify behavioural changes they can make to improve adherence. For both adherence (assessed using electronic pill caps) and depression, CBT-AD performed better than enhanced usual care over the four month treatment period and an eight month follow-up period, but was no better than ISP-AD. However, there was no effect on viral load or the proportion with detectable viral load, the end result of adherence. This may be because 90% of participants had viral suppression at baseline so there was a ceiling effect on improvement, because the increase in adherence may not have been sufficient to reach undetectable viral load or due to problems with measurement errors of adherence. This trial illustrates that psychosocial therapy for ART adherence has potential to improve adherence among people living with HIV. But further studies are necessary – including in LMIC, and restricting participants to people who are not virologically supressed. 

Northern America
United States of America
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Ending HIV deaths in South Africa: progress made but still a long way to go

Mortality trends and differentials in South Africa from 1997 to 2012: second National Burden of Disease Study.

Pillay-van Wyk V, Msemburi W, Laubscher R, Dorrington RE, Groenewald P, Glass T, Nojilana B, Joubert JD, Matzopoulos R, Prinsloo M, Nannan N, Gwebushe N, Vos T, Somdyala N, Sithole N, Neethling I, Nicol E, Rossouw A, Bradshaw D. Lancet Glob Health. 2016 Sep;4(9):e642-53. doi: 10.1016/S2214-109X(16)30113-9.

Background: The poor health of South Africans is known to be associated with a quadruple disease burden. In the second National Burden of Disease (NBD) study, we aimed to analyse cause of death data for 1997-2012 and develop national, population group, and provincial estimates of the levels and causes of mortality.

Method: We used underlying cause of death data from death notifications for 1997-2012 obtained from Statistics South Africa. These data were adjusted for completeness using indirect demographic techniques for adults and comparison with survey and census estimates for child mortality. A regression approach was used to estimate misclassified HIV/AIDS deaths and so-called garbage codes were proportionally redistributed by age, sex, and population group population group (black African, Indian or Asian descent, white [European descent], and coloured [of mixed ancestry according to the preceding categories]). Injury deaths were estimated from additional data sources. Age-standardised death rates were calculated with mid-year population estimates and the WHO age standard. Institute of Health Metrics and Evaluation Global Burden of Disease (IHME GBD) estimates for South Africa were obtained from the IHME GHDx website for comparison.

Findings: All-cause age-standardised death rates increased rapidly since 1997, peaked in 2006 and then declined, driven by changes in HIV/AIDS. Mortality from tuberculosis, non-communicable diseases, and injuries decreased slightly. In 2012, HIV/AIDS caused the most deaths (29.1%) followed by cerebrovascular disease (7.5%) and lower respiratory infections (4.9%). All-cause age-standardised death rates were 1.7 times higher in the province with the highest death rate compared to the province with the lowest death rate, 2.2 times higher in black Africans compared to whites, and 1.4 times higher in males compared with females. Comparison with the IHME GBD estimates for South Africa revealed substantial differences for estimated deaths from all causes, particularly HIV/AIDS and interpersonal violence.

Interpretation: This study related the reversal of HIV/AIDS, non-communicable disease, and injury mortality trends in South Africa during the study period. Mortality differentials show the importance of social determinants, raise concerns about the quality of health services, and provide relevant information to policy makers for addressing inequalities. Differences between GBD estimates for South Africa and this study emphasise the need for more careful calibration of global models with local data.

Abstract   Full-text [free] access 

Editor’s notes: In South Africa in 2012, almost 500 people died every day from HIV or TB. One in every three deaths was associated with HIV or TB. Although these figures represent a substantial decline from the peak of the epidemic impact in 2006, they highlight the enormous challenge still facing this country.

South Africa is one of the few countries in Africa to have a robust civil registration system for deaths. However, there continue to be problems with misclassification of HIV-associated deaths. This analysis relied on somewhat complicated analytical methods to adjust mortality estimates. Only around half of those deaths ultimately defined as HIV associated had been originally coded as such in the registration system. The methods for adjustment differed from those used in the Global Burden of Disease (GBD) study. This explains the quite marked discrepancy in number of deaths attributed to HIV - this study estimated 40% fewer HIV-associated deaths than the GBD study.

This highlights that there is still quite a lot of uncertainty around cause-specific mortality estimates. So, although these data are useful to guide national and provincial priority setting, more fine-grain analysis is required to properly inform public health policies. There is a particular need to unpick the contribution of TB. In this respect, the recent announcement by the South African Department of Science of Technology to establish a network of health and demographic surveillance sites as a key component of the national research infrastructure is very welcome. With established verbal autopsy methods and innovations such as routine linkage to health service records, this will provide a framework to allow a deeper understanding of mortality.

Africa
South Africa
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Challenges in assessing quality in HIV outpatient care

Structure and quality of outpatient care for people living with an HIV infection.

Engelhard EA, Smit C, Nieuwkerk PT, Reiss P, Kroon FP, Brinkman K, Geerlings SE. AIDS Care. 2016 Aug;28(8):1062-72. doi: 10.1080/09540121.2016.1153590. Epub 2016 Mar 13.

Policy-makers and clinicians are faced with a gap of evidence to guide policy on standards for HIV outpatient care. Ongoing debates include which settings of care improve health outcomes, and how many HIV-infected patients a health-care provider should treat to gain and maintain expertise. In this article, we evaluate the studies that link health-care facility and care provider characteristics (i.e., structural factors) to health outcomes in HIV-infected patients. We searched the electronic databases MEDLINE, PUBMED, and EMBASE from inception until 1 January 2015. We included a total of 28 observational studies that were conducted after the introduction of combination antiretroviral therapy in 1996. Three aspects of the available research linking the structure to quality of HIV outpatient care were evaluated: (1) assessed structural characteristics (i.e., health-care facility and care provider characteristics); (2) measures of quality of HIV outpatient care; and (3) reported associations between structural characteristics and quality of care. Rather than scarcity of data, it is the diversity in methodology in the identified studies and the inconsistency of their results that led us to the conclusion that the scientific evidence is too weak to guide policy in HIV outpatient care. We provide recommendations on how to address this heterogeneity in future studies and offer specific suggestions for further reading that could be of interest for clinicians and researchers.

Abstract access

Editor’s notes: The availability of antiretroviral therapy has resulted in remarkable decreases in HIV-associated mortality.  Complexity in the management of HIV infection has however grown along with these advances in treatment. Health-care providers are confronted with challenges associated with antiretroviral therapy including toxicities; drug-drug interactions and drug resistance; and comorbidities and aging among the population living with HIV. In order to achieve optimal health outcomes, care for people living with HIV should be provided at health-care facilities and by care providers with sufficient expertise. A variety of different delivery models have been attempted to achieve this. There are a growing number of studies assessing care delivery models and programmes in outpatient HIV care.  In this article the authors provide an overview of the scientific literature linking health-care facility and care provider characteristics to the quality of HIV outpatient care.

The authors conducted a systematic review of articles that reported an original observational research study with an adult population living with HIV, were conducted after 1996, and that did not focus exclusively on interventions.

The authors acknowledge the limitations of their research. These included a disproportionate number of studies based in the USA and sub-Saharan Africa (thus limited generalisability); diversity in the definition of structural variables; a wide scope of measures of quality of care used in studies; and limited inclusion of peoples’ healthcare experiences. The authors summarise two main implications of their research.  First, they note that their findings suggest that health-care provider experience improves outcomes among people living with HIV although they are unable to make recommendations regarding facility volume requirements for outpatient care. Second, they advocate for the need for research to extend to regions outside the USA and sub-Saharan Africa.  They also note the need for researchers to align their methods of measuring quality including by going beyond HIV-associated morbidity in the evaluation of health outcomes.  Peoples’ preferences and retention in care should also play an important role in the evaluation of the quality of care.

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Real-world barriers to active TB case detection in HIV clinics

Implementation and operational research: use of symptom screening and sputum microscopy testing for active tuberculosis case detection among HIV-infected patients in real-world clinical practice in Uganda.

Roy M, Muyindike W, Vijayan T, Kanyesigye M, Bwana M, Wenger M, Martin J, Geng E. J Acquir Immune Defic Syndr. 2016 Aug 15;72(5):e86-91. doi: 10.1097/QAI.0000000000001067.

Background: The uptake of intensified active TB case-finding among HIV-infected patients using symptom screening is not well understood. We evaluated the rate and completeness of each interim step in the TB pulmonary "diagnostic cascade" to understand real-world barriers to active TB case detection.

Methods: We conducted a cohort analysis of new, antiretroviral therapy-naive, HIV-infected patients who attended a large HIV clinic in Mbarara, Uganda (March 1, 2012-September 30, 2013). We used medical records to extract date of completion of each step in the diagnostic cascade: symptom screen, order, collection, processing, and result. Factors associated with lack of sputum order were evaluated using multivariate Poisson regression and chart review of 50 screen-positive patients.

Results: Of 2613 patients, 2439 (93%) were screened for TB and 682 (28%) screened positive. Only 90 (13.2%) had a sputum order. Of this group, 83% completed the diagnostic cascade, 13% were diagnosed with TB, and 50% had a sputum result within 1 day of their visit. Sputum ordering was associated with WHO stage 3 or 4 HIV disease and greater number of symptoms. The main identifiable reasons for lack of sputum order in chart review were treatment of presumed malaria (51%) or bacterial infection (43%).

Conclusions: The majority of newly enrolled HIV-infected patients who screened positive for suspected TB did not have a sputum order, and those who did were more likely to have more symptoms and advanced HIV disease. Further evaluation of provider behavior in the management of screen-positive patients could improve active TB case detection rates.

Abstract access  

Editor’s notes: This cohort analysis of people enrolling for HIV care at a President’s Emergency Plan for AIDS Relief (PEPFAR) clinic in Uganda used medical record review to identify barriers to active TB case finding in a programmatic setting. This study is unique in evaluating each step along the entire TB diagnostic cascade, from the WHO screening tool, which asks about four symptoms, through to sputum result, in a setting where TB diagnosis was based on sputum microscopy, prior to availability of Xpert ® MTB/RIF.

The authors found high uptake of TB symptom screening at enrolment to HIV care, with cough being the most commonly reported symptom. However, most people with symptoms suggestive of TB were not documented to have had sputum investigation ordered, this being the major point of loss from the TB diagnostic pathway. Given that the prevalence of active TB among people newly testing HIV positive is consistently high in African countries, this represents a substantial missed opportunity for prompt identification and treatment of TB. The study design did not allow in-depth evaluation of the reasons for lack of sputum order since this may not be clearly documented in medical records. Factors such as a person’s inability to produce sputum should also be considered. Ultimately, a high sensitivity, affordable, non-sputum based, point-of-care diagnostic test for TB is necessary to overcome the barriers inherent in the current complex TB diagnostic pathway.

Africa
Uganda
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Accurate country-level data necessary to inform HIV incidence estimates

Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015: the Global Burden of Disease Study 2015.

Wang H, Wolock TM, Carter A, Nguyen G, Kyu HH, Gakidou E, Hay SI, Mills EJ, Trickey A, Msemburi W, Coates MM, Mooney MD, Fraser MS, Sligar A, Salomon J, Larson HJ, Friedman J, Abajobir AA, Abate KH, Abbas KM, Razek MM, Abd-Allah F, Abdulle AM, Abera SF, Abubakar I, Abu-Raddad LJ, Abu-Rmeileh NM, Abyu GY, Adebiyi AO, Adedeji IA, Adelekan AL, Adofo K, Adou AK, Ajala ON, Akinyemiju TF, Akseer N, Lami FH, Al-Aly Z, Alam K, Alam NK, Alasfoor D, Aldhahri SF, Aldridge RW, Alegretti MA, Aleman AV, Alemu ZA, Alfonso-Cristancho R, Ali R, Alkerwi A, Alla F, Mohammad R, Al-Raddadi S, Alsharif U, Alvarez E, Alvis-Guzman N, Amare AT, Amberbir A, Amegah AK, Ammar W, Amrock SM, Antonio CA, Anwari P, Arnlov J, Artaman A, Asayesh H, Asghar RJ, Assadi R, Atique S, Atkins LS, Avokpaho EF, Awasthi A, Quintanilla BP, Bacha U, Badawi A, Barac A, Barnighausen T, Basu A, Bayou TA, Bayou YT, Bazargan-Hejazi S, Beardsley J, Bedi N, Bennett DA, Bensenor IM, Betsu BD, Beyene AS, Bhatia E, Bhutta ZA, Biadgilign S, Bikbov B, Birlik SM, Bisanzio D, Brainin M, Brazinova A, Breitborde NJ, Brown A, Burch M, Butt ZA, Campuzano JC, Cardenas R, Carrero JJ, Castaneda-Orjuela CA, Rivas JC, Catala-Lopez F, Chang HY, Chang JC, Chavan L, Chen W, Chiang PP, Chibalabala M, Chisumpa VH, Choi JY, Christopher DJ, Ciobanu LG, Cooper C, Dahiru T, Damtew SA, Dandona L, Dandona R, das Neves J, de Jager P, De Leo D, Degenhardt L, Dellavalle RP, Deribe K, Deribew A, Des Jarlais DC, Dharmaratne SD, Ding EL, Doshi PP, Driscoll TR, Dubey M, Elshrek YM, Elyazar I, Endries AY, Ermakov SP, Eshrati B, Esteghamati A, Faghmous ID, Farinha CS, Faro A, Farvid MS, Farzadfar F, Fereshtehnejad SM, Fernandes JC, Fischer F, Fitchett JR, Foigt N, Fullman N, Furst T, Gankpe FG, Gebre T, Gebremedhin AT, Gebru AA, Geleijnse JM, Gessner BD, Gething PW, Ghiwot TT, Giroud M, Gishu MD, Glaser E, Goenka S, Goodridge A, Gopalani SV, Goto A, Gugnani HC, Guimaraes MD, Gupta R, Gupta R, Gupta V, Haagsma J, Hafezi-Nejad N, Hagan H, Hailu GB, Hamadeh RR, Hamidi S, Hammami M, Hankey GJ, Hao Y, Harb HL, Harikrishnan S, Haro JM, Harun KM, Havmoeller R, Hedayati MT, Heredia-Pi IB, Hoek HW, Horino M, Horita N, Hosgood HD, Hoy DG, Hsairi M, Hu G, Huang H, Huang JJ, Iburg KM, Idrisov BT, Innos K, Iyer VJ, Jacobsen KH, Jahanmehr N, Jakovljevic MB, Javanbakht M, Jayatilleke AU, Jeemon P, Jha V, Jiang G, Jiang Y, Jibat T, Jonas JB, Kabir Z, Kamal R, Kan H, Karch A, Karema CK, Karletsos D, Kasaeian A, Kaul A, Kawakami N, Kayibanda JF, Keiyoro PN, Kemp AH, Kengne AP, Kesavachandran CN, Khader YS, Khalil I, Khan AR, Khan EA, Khang YH, Khubchandani J, Kim YJ, Kinfu Y, Kivipelto M, Kokubo Y, Kosen S, Koul PA, Koyanagi A, Defo BK, Bicer BK, Kulkarni VS, Kumar GA, Lal DK, Lam H, Lam JO, Langan SM, Lansingh VC, Larsson A, Leigh J, Leung R, Li Y, Lim SS, Lipshultz SE, Liu S, Lloyd BK, Logroscino G, Lotufo PA, Lunevicius R, Razek HM, Mahdavi M, Majdan M, Majeed A, Makhlouf C, Malekzadeh R, Mapoma CC, Marcenes W, Martinez-Raga J, Marzan MB, Masiye F, Mason-Jones AJ, Mayosi BM, McKee M, Meaney PA, Mehndiratta MM, Mekonnen AB, Melaku YA, Memiah P, Memish ZA, Mendoza W, Meretoja A, Meretoja TJ, Mhimbira FA, Miller TR, Mikesell J, Mirarefin M, Mohammad KA, Mohammed S, Mokdad AH, Monasta L, Moradi-Lakeh M, Mori R, Mueller UO, Murimira B, Murthy GV, Naheed A, Naldi L, Nangia V, Nash D, Nawaz H, Nejjari C, Ngalesoni FN, de Dieu Ngirabega J, Nguyen QL, Nisar MI, Norheim OF, Norman RE, Nyakarahuka L, Ogbo FA, Oh IH, Ojelabi FA, Olusanya BO, Olusanya JO, Opio JN, Oren E, Ota E, Padukudru MA, Park HY, Park JH, Patil ST, Patten SB, Paul VK, Pearson K, Peprah EK, Pereira CC, Perico N, Pesudovs K, Petzold M, Phillips MR, Pillay JD, Plass D, Polinder S, Pourmalek F, Prokop DM, Qorbani M, Rafay A, Rahimi K, Rahimi-Movaghar V, Rahman M, Rahman MH, Rahman SU, Rai RK, Rajsic S, Ram U, Rana SM, Rao PV, Remuzzi G, Rojas-Rueda D, Ronfani L, Roshandel G, Roy A, Ruhago GM, Saeedi MY, Sagar R, Saleh MM, Sanabria JR, Santos IS, Sarmiento-Suarez R, Sartorius B, Sawhney M, Schutte AE, Schwebel DC, Seedat S, Sepanlou SG, Servan-Mori EE, Shaikh. Lancet HIV. 2016 Aug;3(8):e361-87. doi: 10.1016/S2352-3018(16)30087-X. Epub 2016 Jul 19.

Background: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.

Methods: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.

Findings: Global HIV incidence reached its peak in 1997, at 3.3 million new infections (95% uncertainty interval [UI] 3.1-3.4 million). Annual incidence has stayed relatively constant at about 2.6 million per year (range 2.5-2.8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38.8 million (95% UI 37.6-40.4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1.8 million deaths (95% UI 1.7-1.9 million) in 2005, to 1.2 million deaths (1.1-1.3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.

Interpretation: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.

Abstract  Full-text [free] access

Editor’s notes: The global estimates for HIV incidence, prevalence, and deaths produced by the Global Burden of Disease (GBD) mathematical modelling approach for 2015 are somewhat higher than those published by UNAIDS in June 2016 prior to the International Conference on AIDS held in Durban in July. Both GBD and UNAIDS agree that as the scale-up of antiretroviral treatment (ART) continues, HIV-associated mortality is declining with the result that HIV prevalence is rising as the number of people living with HIV continues to grow. The metric of critical interest to policy makers and programme planners is HIV incidence, the number of new infections. Each new infection means ART for life, starting from HIV diagnosis now rather than later in disease progression. Both GBD and UNAIDS estimates suggest that globally annual HIV incidence stopped declining after 2005 and has remained persistently high at 2.5 million (2.2-2.7 million) according to GDB and 2.1 million (1.8-2.4 million) according to UNAIDS. Where the estimates differ is at country level, precisely where they can make the most difference to decision making. GBD estimates for HIV incidence for countries in the regions of northern America, Europe, Australasia, and central Asia are significantly lower than the reported numbers of newly diagnosed cases (see the comparison table in the Lancet commentary by Supervie and Costagliola. For example, 85 252 people were newly diagnosed with HIV in the Russian federation in 2014 whereas the GBD estimate for people newly acquiring HIV in 2015 was only 57 340, albeit with a wide range of uncertainly. For the United States of America, the uncertainly bounds around the GBD estimate of 23 040 do not include 44,073, the number of newly diagnosed cases. Furthermore, new diagnoses likely underestimate actual HIV incidence as they include people who acquired HIV in previous years. Estimates for some high prevalence countries are significantly higher than those produced by those countries with UNAIDS support. For example, http://aidsinfo.unaids.org/ illustrates South Africa as having 380 000 (330 000-430 000) new infections while GBD estimates 529 670 (440 940 to 630 390). Modelling estimates are simply estimates but they cannot be confirmatory or even complementary when they are so different. UNAIDS and IHME (GBD) are already working to understand the differences in the two mathematical modelling approaches - their methodologies, parameters, and assumptions - in order to explain important discrepancies at country level. More importantly, improved data collection by countries of the numbers of HIV diagnoses, people accessing and staying on ART, and the proportion of people living with HIV who achieve viral suppression is necessary to monitor progress towards the UNAIDS 90-90-90 treatment target. Enhanced clinical and epidemiological surveillance systems are also key to the creation of more accurate estimates of country HIV incidence, the metric that reflects HIV prevention programme progress and informs budget allocations and programme planning for HIV treatment. 

195 countries
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Improved survival with lymphoma in the antiretroviral therapy era

Evolution of HIV-associated lymphoma over 3 decades.

Ramaswami R, Chia G, Dalla Pria A, Pinato DJ, Parker K, Nelson M, Bower M. J Acquir Immune Defic Syndr. 2016 Jun 1;72(2):177-83. doi: 10.1097/QAI.0000000000000946.

Introduction: The emergence of combined antiretroviral therapy (cART) and improvements in the management of opportunistic infections have altered the HIV epidemic over the last 30 years. We aimed to assess changes to the biology and outcomes of HIV-associated lymphomas over this period at the national center for HIV oncology in the United Kingdom.

Methods: Clinical characteristics at lymphoma diagnosis have been prospectively collected since 1986, along with details of lymphoma treatment and outcomes. The clinical features and outcomes were compared between 3 decades: pre-cART decade (1986-1995), early-cART decade (1996-2005), and late-cART decade (2006-2015).

Results: A total of 615 patients with HIV-associated lymphoma were included in the study: 158 patients in the pre-cART era, 200 patients in the early-cART era, and 257 patients in the late-cART era. In more recent decades, patients were older (P < 0.0001) and had higher CD4 cell counts (P < 0.0001) at lymphoma diagnosis. Over time, there has also been a shift in lymphoma histological subtypes, with an increase in lymphoma subtypes associated with moderate immunosuppression. The overall survival for patients with HIV-associated lymphoma has dramatically improved over the 3 decades (P < 0.0001).

Conclusion: Over the last 30 years, the clinical demographic of HIV-associated lymphomas has evolved, and the outcomes have improved.

Abstract access

Editor’s notes: Lymphomas are the second most common malignancy after Kaposi’s sarcoma among people living with HIV in Europe, Australia and northern America. This study examined how the biology and rates of survival have changed since combination antiretroviral therapy (cART) became available.

People living with HIV and diagnosed with lymphoma over the past thirty years in a specialist oncology centre in the United Kingdom were included in the study. The mean age at diagnosis of lymphoma increased over time, most likely reflecting improvement in life expectancy with cART. As would be expected, the mean CD4 count and the proportion of people with a suppressed viral load at lymphoma diagnosis increased, while proportion with an AIDS-defining illness before lymphoma diagnosis declined significantly.  

This study demonstrated a shift of the histological subtypes of lymphoma that are associated with less severe immunosuppression, for example the proportion of primary CNS lymphoma (PCNSL) and diffuse large B-cell lymphoma (DLBCL), which are associated with severe immunosuppression, declined, while the proportion of Burkitt’s lymphoma and Hodgkin’s lymphoma (associated with less profound immunosuppression) increased.

A key finding of this study was the significantly improved overall survival of people with lymphoma. The improved survival is not explained by changes in histological subtypes of lymphoma over time, as improvement in prognosis was observed for each histological subtype. The substantial improvement in overall survival is attributable to a number of factors. They include the availability of cART, attention to opportunistic infection prophylaxis, improved supportive care for people undergoing lymphoma treatment as well as improved modalities of lymphoma treatment. Such modalities include efficacious drugs that can be safely co-administered with cART, e.g., rituximab, novel agents and use of autologous stem cell transplants.  

Europe
United Kingdom
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Ending deaths in people with TB and HIV – still some way to go

High mortality in tuberculosis patients despite HIV interventions in Swaziland.

Mchunu G, van Griensven J, Hinderaker SG, Kizito W, Sikhondze W, Manzi M, Dlamini T, Harries AD. Public Health Action. 2016 Jun 21;6(2):105-10. doi: 10.5588/pha.15.0081.

Setting: All health facilities providing tuberculosis (TB) care in Swaziland.

Objective: To describe the impact of human immunodeficiency virus (HIV) interventions on the trend of TB treatment outcomes during 2010-2013 in Swaziland; and to describe the evolution in TB case notification, the uptake of HIV testing, antiretroviral therapy (ART) and cotrimoxazole preventive therapy (CPT), and the proportion of TB-HIV co-infected patients with adverse treatment outcomes, including mortality, loss to follow-up and treatment failure.

Design: A retrospective descriptive study using aggregated national TB programme data.

Results: Between 2010 and 2013, TB case notifications in Swaziland decreased by 40%, HIV testing increased from 86% to 96%, CPT uptake increased from 93% to 99% and ART uptake among TB patients increased from 35% to 75%. The TB-HIV co-infection rate remained around 70% and the proportion of TB-HIV cases with adverse outcomes decreased from 36% to 30%. Mortality remained high, at 14-16%, over the study period, and anti-tuberculosis treatment failure rates were stable over time (<5%).

Conclusion: Despite high CPT and ART uptake in TB-HIV patients, mortality remained high. Further studies are required to better define high-risk patient groups, understand the reasons for death and design appropriate interventions.

Abstract  Full-text [free] access 

Editor’s notes: This article adds to the body of evidence describing a reduction in TB case notifications at national level at a time of increasing coverage of antiretroviral therapy. Despite the apparent strengthening of the HIV treatment cascade in people with TB, mortality remained high. Around one in seven people with TB and HIV died during TB treatment, and additional deaths may have occurred in people lost to follow-up or with no outcome evaluation.

This analysis using aggregated data does not allow for detailed understanding of why people with TB and HIV died. The authors raise a number of important questions arising from these results. To achieve World Health Organization End TB target of reducing TB deaths by 90% by 2030, we need to understand where to focus resources for maximum impact.

Although not the focus of this paper, it is notable that there appeared to be a relatively stable TB case notification rate in HIV negative people across the four-year study period. This is a reminder that although TB/HIV programmes may be the key to reducing TB mortality, broader population-level programmes to interrupt TB transmission will be required to drive down TB incidence rates.           

Africa
Swaziland
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