Articles tagged as "Malawi"

Routine use of steroids harmful in cryptococcal meningitis

Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis.

Beardsley J, Wolbers M, Kibengo FM, Ggayi AB, Kamali A, Cuc NT, Binh TQ, Chau NV, Farrar J, Merson L, Phuong L, Thwaites G, Van Kinh N, Thuy PT, Chierakul W, Siriboon S, Thiansukhon E, Onsanit S, Supphamongkholchaikul W, Chan AK, Heyderman R, Mwinjiwa E, van Oosterhout JJ, Imran D, Basri H, Mayxay M, Dance D, Phimmasone P, Rattanavong S, Lalloo DG, Day JN, CryptoDex Investigations. N Engl J Med. 2016 Feb 11;374(6):542-54. doi: 10.1056/NEJMoa1509024.

Background: Cryptococcal meningitis associated with human immunodeficiency virus (HIV) infection causes more than 600 000 deaths each year worldwide. Treatment has changed little in 20 years, and there are no imminent new anticryptococcal agents. The use of adjuvant glucocorticoids reduces mortality among patients with other forms of meningitis in some populations, but their use is untested in patients with cryptococcal meningitis.

Methods: In this double-blind, randomized, placebo-controlled trial, we recruited adult patients with HIV-associated cryptococcal meningitis in Vietnam, Thailand, Indonesia, Laos, Uganda, and Malawi. All the patients received either dexamethasone or placebo for 6 weeks, along with combination antifungal therapy with amphotericin B and fluconazole.

Results: The trial was stopped for safety reasons after the enrollment of 451 patients. Mortality was 47% in the dexamethasone group and 41% in the placebo group by 10 weeks (hazard ratio in the dexamethasone group, 1.11; 95% confidence interval [CI], 0.84 to 1.47; P=0.45) and 57% and 49%, respectively, by 6 months (hazard ratio, 1.18; 95% CI, 0.91 to 1.53; P=0.20). The percentage of patients with disability at 10 weeks was higher in the dexamethasone group than in the placebo group, with 13% versus 25% having a prespecified good outcome (odds ratio, 0.42; 95% CI, 0.25 to 0.69; P<0.001). Clinical adverse events were more common in the dexamethasone group than in the placebo group (667 vs. 494 events, P=0.01), with more patients in the dexamethasone group having grade 3 or 4 infection (48 vs. 25 patients, P=0.003), renal events (22 vs. 7, P=0.004), and cardiac events (8 vs. 0, P=0.004). Fungal clearance in cerebrospinal fluid was slower in the dexamethasone group. Results were consistent across Asian and African sites.

Conclusions: Dexamethasone did not reduce mortality among patients with HIV-associated cryptococcal meningitis and was associated with more adverse events and disability than was placebo.

Abstract  Full-text [free] access 

Editor’s notes: Outcomes from cryptococcal meningitis in people living with HIV are very poor. This was highlighted here. Three out of five people overall had died or were severely disabled ten weeks after enrolment. This clinical trial provides strong evidence that steroids cause more harm than good and therefore routine use should not be recommended. Dexamethasone was not only associated with higher risk of death or disability but also with higher risk of significant adverse events, particularly bacterial sepsis.

The majority of deaths occurred early, in the first three weeks. Most participants were ART naïve and severely immunosuppressed (CD4+ cell count <50 cells/µL) and most deaths look to have occurred prior to the scheduled start of antiretroviral therapy. This may also partly explain the low frequency of immune reconstitution inflammatory syndrome (IRIS) and the lack of any observed benefit of dexamethasone in reducing IRIS.

Although dexamethasone was associated with greater decline in intracranial pressure, this did not translate into improved neurological outcomes. All participants had regular lumbar punctures for pressure monitoring. This might have limited the potential to observe a benefit from dexamethasone. Some explanation for the adverse outcomes might come from the impaired fungal clearance in cerebrospinal fluid – a marker of poor outcomes in previous studies. It should be noted that antifungal treatment in this trial was suboptimal. The combination of amphotericin and flucytosine was not used, despite evidence of improved outcomes and more rapid fungal clearance with this regimen.

While the search should go on for better treatment strategies, the findings in this study emphasise the importance of prevention, focused firmly, on earlier HIV diagnosis and treatment.  

Comorbidity, HIV Treatment
Indonesia, Laos, Malawi, Thailand, Uganda, Viet Nam
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Spatial analysis methods to improve localised estimates of HIV prevalence

Evaluation of geospatial methods to generate subnational HIV prevalence estimates for local level planning.

Anderson SJ, Subnational Estimates Working Group of the HIVMC. AIDS. 2016 Feb 25. [Epub ahead of print]

Objective: There is evidence of substantial subnational variation in the HIV epidemic. However, robust spatial HIV data are often only available at high levels of geographic aggregation and not at the finer resolution needed for decision making. Therefore, spatial analysis methods that leverage available data to provide local estimates of HIV prevalence may be useful. Such methods exist but have not been formally compared when applied to HIV.

Design/methods: Six candidate methods - including those used by UNAIDS to generate maps and a Bayesian geostatistical approach applied to other diseases- were used to generate maps and subnational estimates of HIV prevalence across three countries using cluster level data from household surveys. Two approaches were used to assess the accuracy of predictions: (1) internal validation, whereby a proportion of input data is held back (test dataset) to challenge predictions, (2) comparison with location specific data from household surveys in earlier years.

Results: Each of the methods can generate usefully accurate predictions of prevalence at unsampled locations, with the magnitude of the error in predictions similar across approaches. However, the Bayesian geostatistical approach consistently gave marginally the strongest statistical performance across countries and validation procedures.

Conclusions: Available methods may be able to furnish estimates of HIV prevalence at finer spatial scales than the data currently allow. The subnational variation revealed can be integrated into planning to ensure responsiveness to the spatial features of the epidemic. The Bayesian geostatistical approach is a promising strategy for integrating HIV data to generate robust local estimates.

Abstract access  

Editor’s notes: Data from intensively monitored populations indicates that large differences in HIV prevalence can be seen across small geographic spaces. Understanding these localised spatial variations within a generalised epidemic can enable HIV programme resources to be used most effectively. However the data required for such localised estimation are often lacking. As a result modelling strategies must be used to predict local variation based on the best available data.

This study compares six different geospatial methods of estimating local HIV prevalence. The methods can be categorised by whether or not they use ancillary information such as road networks to improve their predictions and also whether they generated continuously changing prevalence surfaces (like map contours) or gave discrete estimates for geographic sub-regions e.g. districts.

While all methods produced reasonable overall levels of performance, those using a Bayesian geostatistical approach illustrated marginally better predictive accuracies. The levels of accuracy appeared more dependent on the national prevalence than the choice of model used.

The authors conclude by setting out a strategy for improvement of the models, principally through integrating additional data from sources such as antiretroviral therapy and prevention of mother-to-child transmission programmes, antenatal clinic surveys and case based reporting. 

Africa
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The power of PEPFAR programmes: estimates of infections averted and life years gained in Africa

Estimating the impact of the US President's Emergency Plan for AIDS Relief on HIV treatment and prevention programmes in Africa.

Heaton LM, Bouey PD, Fu J, Stover J, Fowler TB, Lyerla R, Mahy M. Sex Transm Infect. 2015 Dec;91(8):615-20. doi: 10.1136/sextrans-2014-051991. Epub 2015 Jun 8.

Background: Since 2004, the US President's Emergency Plan for AIDS Relief (PEPFAR) has supported the tremendous scale-up of HIV prevention, care and treatment services, primarily in sub-Saharan Africa. We evaluate the impact of antiretroviral treatment (ART), prevention of mother-to-child transmission (PMTCT) and voluntary medical male circumcision (VMMC) programmes on survival, mortality, new infections and the number of orphans from 2004 to 2013 in 16 PEPFAR countries in Africa.

Methods: PEPFAR indicators tracking the number of persons receiving ART for their own health, ART regimens for PMTCT and biomedical prevention of HIV through VMMC were collected across 16 PEPFAR countries. To estimate the impact of PEPFAR programmes for ART, PMTCT and VMMC, we compared the current scenario of PEPFAR-supported interventions to a counterfactual scenario without PEPFAR, and assessed the number of life years gained (LYG), number of orphans averted and HIV infections averted. Mathematical modelling was conducted using the SPECTRUM modelling suite V.5.03.

Results: From 2004 to 2013, PEPFAR programmes provided support for a cumulative number of     24 565 127 adults and children on ART, 4 154 878 medical male circumcisions, and ART for PMTCT among 4 154 478 pregnant women in 16 PEPFAR countries. Based on findings from the model, these efforts have helped avert 2.9 million HIV infections in the same period. During 2004-2013, PEPFAR ART programmes alone helped avert almost 9 million orphans in 16 PEPFAR countries and resulted in 11.6 million LYG.

Conclusions: Modelling results suggest that the rapid scale-up of PEPFAR-funded ART, PMTCT and VMMC programmes in Africa during 2004-2013 led to substantially fewer new HIV infections and orphaned children during that time and longer lives among people living with HIV. Our estimates do not account for the impact of the PEPFAR-funded non-biomedical interventions such as behavioural and structural interventions included in the comprehensive HIV prevention, care and treatment strategy used by PEPFAR countries. Therefore, the number of HIV infections and orphans averted and LYG may be underestimated by these models.

Abstract access

Editor’s notes: The President’s Emergency Plan for AIDS Relief (PEPFAR) was initiated in 2004 with $42 billion spent up until the end of 2013. Despite limitations in monitoring the overall contribution of PEPFAR to individual programmes, this article attempts to provide an overview of PEPFAR support for ART, prevention of mother to child transmission and voluntary medical male circumcision (VMMC) programmes using the 2014 version of Spectrum Software model. The Spectrum modules used included DemProj, AIDS Impact Model (AIM) and Goals, which interact to model the impact and future course of the HIV epidemic at the population level.  An estimate of PEPFAR’s contribution was obtained by subtracting it from the total for the national programme statistics reported by UNAIDS on ART, PMTCT and VMMC.

The baseline scenario of PEPFAR-supported programmes in 2013 was compared to a counterfactual scenario, which subtracts the direct contribution of PEPFAR. The results estimate that the combined programmes have averted 2.7 million infections in Africa, with over 11.5 million life years gained and the aversion of almost nine million orphans. Other key population programmes that the funding supported including gender equity and health strengthening were not evaluated and therefore, the estimate for impact may be conservative. A limitation of the analysis is that it is unable to predict the national response without PEPFAR and the impact of ART calculated by the model is sensitive to the distribution of new ART patients by CD4 count at the initiation of treatment. In addition, few countries have sufficient death registration systems to validate mortality estimates, which may result in the accomplishments of PEPFAR’s impact being overestimated. However, with the operation of PEPFAR in a larger context of partnership consortiums, an improvement in evaluation methods will be necessary. 

Africa
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Untreated maternal HIV infection and poor perinatal outcomes

Perinatal outcomes associated with maternal HIV infection: a systematic review and meta-analysis.

Wedi CO, Kirtley S, Hopewell S, Corrigan R, Kennedy SH, Hemelaar J. Lancet HIV. 2016 Jan;3(1):e33-48. doi: 10.1016/S2352-3018(15)00207-6. Epub 2015 Nov 27.

Background: The HIV pandemic affects 36.9 million people worldwide, of whom 1.5 million are pregnant women. 91% of HIV-positive pregnant women reside in sub-Saharan Africa, a region that also has very poor perinatal outcomes. We aimed to establish whether untreated maternal HIV infection is associated with specific perinatal outcomes.

Methods: We did a systematic review and meta-analysis of the scientific literature by searching PubMed, CINAHL (Ebscohost), Global Health (Ovid), EMBASE (Ovid), and the Cochrane Central Register of Controlled Trials and four clinical trial databases (WHO International Clinical Trials Registry Platform, the Pan African Clinical Trials Registry, the ClinicalTrials.gov database, and the ISRCTN Registry) for studies published from Jan 1, 1980, to Dec 7, 2014. Two authors independently reviewed the studies retrieved by the scientific literature search, identified relevant studies, and extracted the data. We investigated the associations between maternal HIV infection in women naive to antiretroviral therapy and 11 perinatal outcomes: preterm birth, very preterm birth, low birthweight, very low birthweight, term low birthweight, preterm low birthweight, small for gestational age, very small for gestational age, miscarriage, stillbirth, and neonatal death. We included prospective and retrospective cohort studies and case-control studies reporting perinatal outcomes in HIV-positive women naive to antiretroviral therapy and HIV-negative controls. We used a random-effects model for the meta-analyses of specific perinatal outcomes. We did subgroup and sensitivity analyses and assessed the effect of adjustment for confounders. This systematic review and meta-analysis is registered with PROSPERO, number CRD42013005638.

Findings: Of 60 750 studies identified, we obtained data from 35 studies (20 prospective cohort studies, 12 retrospective cohort studies, and three case-control studies) including 53 623 women. Our meta-analyses of prospective cohort studies show that maternal HIV infection is associated with an increased risk of preterm birth (relative risk 1.50, 95% CI 1.24-1.82), low birthweight (1.62, 1.41-1.86), small for gestational age (1.31, 1.14-1.51), and stillbirth (1.67, 1.05-2.66). Retrospective cohort studies also suggest an increased risk of term low birthweight (2.62, 1.15-5.93) and preterm low birthweight (3.25, 2.12-4.99). The strongest and most consistent evidence for these associations is identified in sub-Saharan Africa. No association was identified between maternal HIV infection and very preterm birth, very small for gestational age, very low birthweight, miscarriage, or neonatal death, although few data were available for these outcomes. Correction for confounders did not affect the significance of these findings.

Interpretation: Maternal HIV infection in women who have not received antiretroviral therapy is associated with preterm birth, low birthweight, small for gestational age, and stillbirth, especially in sub-Saharan Africa. Research is needed to assess how antiretroviral therapy regimens affect these perinatal outcomes.

Abstract access 

Editor’s notes:  Maternal HIV infection is associated with maternal morbidity and mortality and risk of mother-to-child transmission of HIV. Whether maternal HIV infection affects perinatal outcomes, which are major contributors to poor health worldwide, is less well understood. This systematic review and meta-analysis of retrospective and prospective cohort studies and case-control studies demonstrates that untreated maternal HIV infection is associated with increased risk of pre-term birth, low birthweight, small for gestational age and stillbirth. The risk of adverse perinatal outcomes appeared to increase with more advanced HIV disease, although only three of the 35 studies reported perinatal outcomes according to HIV disease stage. These findings persisted even after controlling for potential confounding factors and irrespective of the method used for determining gestational age. None of the studies used a first trimester ultrasound scan, the gold standard for determining gestational age. The association of perinatal outcomes with the infant’s HIV status was not investigated. The strongest evidence for these associations was found in sub-Saharan Africa, where the majority of the studies were conducted.

These findings suggest that HIV is an important contributor to the global burden of perinatal and child morbidity and mortality particularly in countries with the highest burden of maternal HIV infection.     Sub-Saharan Africa has the highest rates of stillbirths and neonatal deaths and is also the region where more than 90% of the world’s pregnant women living with HIV reside.

This study has important implications. Firstly, the coverage of antiretroviral therapy (ART) among pregnant women worldwide still remains suboptimal (estimated to be 68% in 2013), exposing women living with untreated HIV to an increased risk of adverse perinatal outcomes. The biological mechanisms underlying adverse perinatal outcomes in the context of HIV infection are not understood. ART in pregnancy may also adversely affect perinatal outcomes, and there is a pressing need to investigate this as ART is rapidly scaled up.     

Africa, Europe, Northern America
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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.

Abstract  Full-text [free] access

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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Predicting acute HIV infection in key populations

Targeted screening of at-risk adults for acute HIV-1 infection in sub-Saharan Africa.

Sanders EJ, Wahome E, Powers KA, Werner L, Fegan G, Lavreys L, Mapanje C, McClelland RS, Garrett N, Miller WC, Graham SM. AIDS. 2015 Dec;29 Suppl 3:S221-30. doi: 10.1097/QAD.0000000000000924.

Background: Patients with acute HIV-1 infection (AHI) have elevated infectivity, but cannot be diagnosed using antibody-based testing. Approaches to screen patients for AHI are urgently needed to enable counselling and treatment to reduce onward transmission.

Methods: We pooled data from four African studies of high-risk adults that evaluated symptoms and signs compatible with acute retroviral syndrome and tested for HIV-1 at each visit. AHI was defined as detectable plasma viral load or p24 antigen in an HIV-1-antibody-negative patient who subsequently seroconverted. Using generalized estimating equation, we identified symptoms, signs, and demographic factors predictive of AHI, adjusting for study site. We assigned a predictor score to each statistically significant predictor based on its beta coefficient, summing predictor scores to calculate a risk score for each participant. We evaluated the performance of this algorithm overall and at each site.

Results: We compared 122 AHI visits with 45 961 visits by uninfected patients. Younger age (18-29 years), fever, fatigue, body pains, diarrhoea, sore throat, and genital ulcer disease were independent predictors of AHI. The overall area under the receiver operating characteristics curve (AUC) for the algorithm was 0.78, with site-specific AUCs ranging from 0.61 to 0.89. A risk score of at least 2 would indicate AHI testing for 5-50% of participants, substantially decreasing the number needing testing.

Conclusion: Our targeted risk score algorithm based on seven characteristics reduced the number of patients needing AHI testing and had good performance overall. We recommend this risk score algorithm for use by HIV programs in sub-Saharan Africa with capacity to test high-risk patients for AHI.

Abstract  Full-text [free] access

Editor’s notes: This analysis adds to the literature around the performance of risk score algorithms to guide testing for acute HIV infection (AHI). The four studies included in this analysis involved key populations in different African settings. In common with previous analyses, genital ulcer disease had by far the strongest association with AHI. The derived algorithm had modest accuracy overall and poor performance in South Africa, where symptoms and signs were particularly infrequent.

Most studies included in this analysis were cohort studies following key individuals. Whether or not algorithms based on recording of symptoms and signs during intensive follow-up for AHI can be translated for use in a real world situation of unselected people presenting for health care remains unproven. Ultimately, we really need evidence about the impact and cost-effectiveness of detecting AHI in different populations. This is in order to define the role of testing for AHI, and in particular whether rationalising testing with algorithms such as this is necessary (especially for key populations).   

Africa
Kenya, Malawi, South Africa
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HIV contributes to stroke among young people

HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults: A case-control study.

Benjamin LA, Corbett EL, Connor MD, Mzinganjira H, Kampondeni S, Choko A, Hopkins M, Emsley HC, Bryer A, Faragher B, Heyderman RS, Allain TJ, Solomon T. Neurology. 2015 Dec 18. pii: 10.1212/WNL.0000000000002278. [Epub ahead of print]

Objective: To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults.

Methods: We performed a case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex, and place of residence, using Global Positioning System for random selection. Multivariate logistic regression models were used for case-control comparisons.

Results: HIV infection (population attributable fraction [PAF] 15%) and hypertension (PAF 46%) were strongly linked to stroke. HIV was the predominant risk factor for young stroke (≤45 years), with a prevalence of 67% and an adjusted odds ratio (aOR) (95% confidence interval) of 5.57 (2.43-12.8) (PAF 42%). There was an increased risk of a stroke in patients with untreated HIV infection (aOR 4.48 [2.44-8.24], p < 0.001), but the highest risk was in the first 6 months after starting antiretroviral therapy (ART) (aOR 15.6 [4.21-46.6], p < 0.001); this group had a lower median CD4+ T-lymphocyte count (92 vs 375 cells/mm3, p = 0.004). In older participants (HIV prevalence 17%), HIV was associated with stroke, but with a lower PAF than hypertension (5% vs 68%). There was no interaction between HIV and hypertension on stroke risk.

Conclusions: In a population with high HIV prevalence, where stroke incidence is increasing, we have shown that HIV is an important risk factor. Early ART use in immunosuppressed patients poses an additional and potentially treatable stroke risk. Immune reconstitution inflammatory syndrome may be contributing to the disease mechanisms.

Abstract Full-text [free] access

Editor’s notes: Stroke incidence is increasing across sub-Saharan Africa. Globally, hypertension accounts for most of the strokes. However, in sub-Saharan Africa, stroke is not uncommon among younger people, among whom the prevalence of hypertension is low. Therefore other factors may play a role.

This article reports on a case-control study with prospective recruitment of cases and community controls, examining the role of HIV, antiretroviral therapy, and the interaction between HIV and hypertension as risk factors for stroke in a setting with high HIV prevalence.

The investigators confirmed 86% of their cases with brain imaging, and found that the majority (78%) had findings consistent with ischemic stroke. Not surprisingly they found that overall, hypertension accounted for about half (46%) of the stroke cases. Interestingly only one-quarter of all people with hypertension in the study (cases and controls) were on hypertensive treatment.

However, among younger people (≤45 years) with stroke, HIV infection was the most important risk factor and accounted for 42% of the cases. HIV-positive people experienced the greatest risk of stroke during their first six months after ART initiation.

The HIV-positive stroke cases had a lower CD4 cell count compared to HIV-positive controls on the same duration of ART. Immunosuppression is a risk factor for immune constitution inflammatory syndrome (IRIS), and IRIS could thus be a plausible mechanism of stroke among people initiating ART.

The results of this study reinforce the need to start ART before people have advanced immunosuppression, which will reduce IRIS-associated morbidity. The latest WHO guidelines, ‘Treat all’, which recommend starting all HIV-positive people on antiretroviral therapy as soon after diagnosis as possible, have the potential to contribute to this.  

Africa
Malawi
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Violence experience of women living with HIV: a global study

Violence. Enough already: findings from a global participatory survey among women living with HIV.

Orza L, Bewley S, Chung C, Crone ET, Nagadya H, Vazquez M, Welbourn A. J Int AIDS Soc. 2015 Dec 1;18(6 Suppl 5):20285. doi: 10.7448/IAS.18.6.20285. eCollection 2015.

Introduction: Women living with HIV are vulnerable to gender-based violence (GBV) before and after diagnosis, in multiple settings. This study's aim was to explore how GBV is experienced by women living with HIV, how this affects women's sexual and reproductive health (SRH) and human rights (HR), and the implications for policymakers.

Methods: A community-based, participatory, user-led, mixed-methods study was conducted, with women living with HIV from key affected populations. Simple descriptive frequencies were used for quantitative data. Thematic coding of open qualitative responses was performed and validated with key respondents.

Results: In total, 945 women living with HIV from 94 countries participated in the study. Eighty-nine percent of 480 respondents to an optional section on GBV reported having experienced or feared violence, either before, since and/or because of their HIV diagnosis. GBV reporting was higher after HIV diagnosis (intimate partner, family/neighbours, community and health settings). Women described a complex and iterative relationship between GBV and HIV occurring throughout their lives, including breaches of confidentiality and lack of SRH choice in healthcare settings, forced/coerced treatments, HR abuses, moralistic and judgemental attitudes (including towards women from key populations), and fear of losing child custody. Respondents recommended healthcare practitioners and policymakers address stigma and discrimination, training, awareness-raising, and HR abuses in healthcare settings.

Conclusions: Respondents reported increased GBV with partners and in families, communities and healthcare settings after their HIV diagnosis and across the life-cycle. Measures of GBV must be sought and monitored, particularly within healthcare settings that should be safe. Respondents offered policymakers a comprehensive range of recommendations to achieve their SRH and HR goals. Global guidance documents and policies are more likely to succeed for the end-users if lived experiences are used.

Abstract  Full-text [free] access

Editor’s notes: Violence against women who are living with HIV is common globally. This paper reports on a study of 832 women living with HIV from 94 countries who participated in an online survey, recruited through a non-random snowball sampling model. The survey comprised quantitative and qualitative (free text) components. Participants included women who had ever or were currently using injection drugs (14%), who had ever or were currently selling sex (14%), and who had ever or were currently homeless (14%). Lifetime experience of violence among respondents was high (86%). Perpetrators included: intimate partner (59%), family member / neighbour (45%), community member (53%), health care workers (53%) and police, military, prison or detention services (17%). Findings suggest that violence is not a one off occurrence and cannot easily be packaged as a cause or a consequence of HIV. Instead violence occurs throughout women’s lives, takes multiple forms, and has a complex and iterative relationship with HIV.

The study population did not represent all women living with HIV, and was biased towards women with internet access who have an activist interest. Nonetheless, the study provides further evidence of the breadth and frequency of gender based violence experienced by women living with HIV. Key recommendations for policy makers include training of health care workers working in sexual and reproductive services to offer non-discriminatory services to women living with HIV and to effectively respond to disclosures of gender based violence (such as intimate partner violence) as part of the package of care.

Algeria, Angola, Argentina, Armenia, Australia, Austria, Azerbaijan, Belarus, Belgium, Belize, Bolivarian Republic of Venezuela, Bolivia, Botswana, Burkina Faso, Burundi, Cambodia, Cameroon, Canada, Chile, China, Colombia, Costa Rica, Côte d'Ivoire, Czech Republic, Democratic Republic of the Congo, Denmark, Dominican Republic, Ecuador, El Salvador, Estonia, Ethiopia, France, Gabon, Germany, Ghana, Greece, Guatemala, Honduras, Hungary, India, Indonesia, Ireland, Italy, Jamaica, Kazakhstan, Kenya, Kyrgyzstan, Lesotho, Malawi, Mali, Mexico, Moldova, Morocco, Mozambique, Myanmar, Namibia, Nepal, Netherlands, New Zealand, Nicaragua, Nigeria, Norway, Panama, Paraguay, Peru, Poland, Republic of the Congo, Romania, Russian Federation, Rwanda, Serbia, South Africa, Spain, Sri Lanka, Sudan, Swaziland, Switzerland, Tajikistan, Togo, Transdniestria, Turkey, Uganda, Ukraine, United Kingdom, United Republic of Tanzania, United States of America, Uruguay, Uzbekistan, Viet Nam, Zambia, Zimbabwe
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Violence and educational outcomes among young children in South Africa and Malawi

Exposure to violence predicts poor educational outcomes in young children in South Africa and Malawi.

Sherr L, Hensels IS, Skeen S, Tomlinson M, Roberts KJ, Macedo A. Int Health. 2015 Dec 17. pii: ihv070. [Epub ahead of print]

Background: Violence during childhood may affect short and long-term educational factors. There is scant literature on younger children from resource poor settings.

Methods: This study assessed child violence experiences (harsh punishment and exposure to domestic or community violence) and school enrolment, progress and attendance in children attending community-based organisations in South Africa and Malawi (n=989) at baseline and at 15 months' follow-up, examining differential experience of HIV positive, HIV affected and HIV unaffected children.

Results: Violence exposure was high: 45.4% experienced some form of psychological violence, 47.8% physical violence, 46.7% domestic violence and 41.8% community violence. Primary school enrolment was 96%. Violence was not associated with school enrolment at baseline but, controlling for baseline, children exposed to psychological violence for discipline were more than ten times less likely to be enrolled at follow-up (OR 0.09; 95% CI 0.01 to 0.57). Harsh discipline was associated with poor school progress. For children HIV positive a detrimental effect of harsh physical discipline was found on school performance (OR 0.10; 95% CI 0.02 to 0.61).

Conclusion: Violence experiences were associated with a number of educational outcomes, which may have long-term consequences. Community-based organisations may be well placed to address such violence, with a particular emphasis on the challenges faced by children who are HIV positive.

Abstract  Full-text [free] access

Editor’s notes: There is substantial evidence that demonstrates the negative effects of the experience of violence in childhood on child mental health. However, there is little evidence on the impact of violence on educational outcomes. This is due to measurement and study design, such as data being primarily cross-sectional and studies being confined to adolescents, where younger children are excluded. This study reports data from a longitudinal study of young children aged 4–13 years affected by HIV enrolled at community-based organisations (CBOs) in South Africa and Malawi. The study examined the relationship between exposure to violence at home or in the community on educational outcomes at baseline and follow-up (12–15 months later). In particular, attention was given to HIV positive and HIV affected children in order to explore the effects of HIV as a factor of either violence experience or educational risk in this age group. HIV affected children are children who may not be HIV positive themselves, but living in a household with a HIV positive member.

In this sample of young children (n=989), close to 14% were HIV positive. School enrolment and attendance was high, although HIV positive children had slightly lower attendance and enrolment in the correct grade for their age, compared to HIV affected children. At baseline, overall exposure to violence at home and in the community was very high. Over half of the sample had been exposed to two or more types of violence, whereas less than one in six reported no violence exposure at all. At both baseline and at follow-up, there was no association found between community violence and school enrolment and attendance or grade progression. In terms of violence experienced at home (domestic violence), at baseline there was an association with grade progression for children in households with no HIV. At follow-up, in particular for children living with HIV, use of physical violence to discipline the child had a detrimental effect on grade progression. Furthermore, at follow-up, the use of psychological violence to discipline children had an effect on school enrolment. Hence, children of caregivers using psychological violence for discipline were significantly less likely to be enrolled in school at follow-up, if they were not enrolled at baseline. Thus, findings from this study highlight that despite high rates of violence exposure in this population, children who are HIV positive, in particular, appear to be most at risk of poor educational outcomes. This is likely to be due to a range of inter-related risk factors that affect educational outcomes: parental death, shifting care arrangements, change in school, illness-induced poverty and increased care-giving responsibilities.  All these factors might affect a child’s ability to access schooling and perform well in the context of HIV. As shown, educational outcomes were specifically linked to harsh punishment, as opposed to community or domestic violence. Thus, CBOs that provide services for children affected by HIV might be key to intervening on this issue. Furthermore, younger children in HIV endemic countries are particularly vulnerable and educational achievement in the early years is an important pre-requisite for ongoing educational milestones.  

Africa
Malawi, South Africa
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