Articles tagged as "Lesotho"

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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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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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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Expanding ART access: increasing costs

The HIV treatment gap: estimates of the financial resources needed versus available for scale-up of antiretroviral therapy in 97 countries from 2015 to 2020.

Dutta A, Barker C, Kallarakal A. PLoS Med. 2015 Nov 24;12(11):e1001907. doi: 10.1371/journal.pmed.1001907. eCollection 2015.

Background: The World Health Organization (WHO) released revised guidelines in 2015 recommending that all people living with HIV, regardless of CD4 count, initiate antiretroviral therapy (ART) upon diagnosis. However, few studies have projected the global resources needed for rapid scale-up of ART. Under the Health Policy Project, we conducted modeling analyses for 97 countries to estimate eligibility for and numbers on ART from 2015 to 2020, along with the facility-level financial resources required. We compared the estimated financial requirements to estimated funding available.

Methods and findings: Current coverage levels and future need for treatment were based on country-specific epidemiological and demographic data. Simulated annual numbers of individuals on treatment were derived from three scenarios: (1) continuation of countries' current policies of eligibility for ART, (2) universal adoption of aspects of the WHO 2013 eligibility guidelines, and (3) expanded eligibility as per the WHO 2015 guidelines and meeting the Joint United Nations Programme on HIV/AIDS "90-90-90" ART targets. We modeled uncertainty in the annual resource requirements for antiretroviral drugs, laboratory tests, and facility-level personnel and overhead.

We estimate that 25.7 (95% CI 25.5, 26.0) million adults and 1.57 (95% CI 1.55, 1.60) million children could receive ART by 2020 if countries maintain current eligibility plans and increase coverage based on historical rates, which may be ambitious. If countries uniformly adopt aspects of the WHO 2013 guidelines, 26.5 (95% CI 26.0 27.0) million adults and 1.53 (95% CI 1.52, 1.55) million children could be on ART by 2020. Under the 90-90-90 scenario, 30.4 (95% CI 30.1, 30.7) million adults and 1.68 (95% CI 1.63, 1.73) million children could receive treatment by 2020. The facility-level financial resources needed for scaling up ART in these countries from 2015 to 2020 are estimated to be US$45.8 (95% CI 45.4, 46.2) billion under the current scenario, US$48.7 (95% CI 47.8, 49.6) billion under the WHO 2013 scenario, and US$52.5 (95% CI 51.4, 53.6) billion under the 90-90-90 scenario. After projecting recent external and domestic funding trends, the estimated 6-y financing gap ranges from US$19.8 billion to US$25.0 billion, depending on the costing scenario and the U.S. President's Emergency Plan for AIDS Relief contribution level, with the gap for ART commodities alone ranging from US$14.0 to US$16.8 billion. The study is limited by excluding above-facility and other costs essential to ART service delivery and by the availability and quality of country- and region-specific data.

Conclusions: The projected number of people receiving ART across three scenarios suggests that countries are unlikely to meet the 90-90-90 treatment target (81% of people living with HIV on ART by 2020) unless they adopt a test-and-offer approach and increase ART coverage. Our results suggest that future resource needs for ART scale-up are smaller than stated elsewhere but still significantly threaten the sustainability of the global HIV response without additional resource mobilization from domestic or innovative financing sources or efficiency gains. As the world moves towards adopting the WHO 2015 guidelines, advances in technology, including the introduction of lower-cost, highly effective antiretroviral regimens, whose value are assessed here, may prove to be "game changers" that allow more people to be on ART with the resources available.

Abstract Full-text [free] access

Editor’s notes: This is a complex and important paper that seeks to understand the financial requirements necessary to: a) continue countries’ current policies of eligibility for ART, b) roll out universal adoption of certain aspects of WHO 2013 eligibility guidelines, and c) expand eligibility as per WHO 2015 guidelines and meeting the Joint United Nations Programme on HIV/AIDS ‘90-90-90’ targets.

The authors estimated the number of adults and children eligible for and receiving HIV treatment, as well as the cost of providing ART in 97 countries across six regions, covering different income levels. They estimated that 25.7 million adults and 1.57 million children could receive ART by 2020 if countries maintain the current eligibility strategies. If countries adopted WHO 2013 eligibility guidelines, 26.5 million adults and 1.53 million children would be on ART by 2020, and if they adopted the 90-90-90 scenario, 30.4 million adults and 1.68 million children could receive treatment by then. The financial resources necessary for this scale up are estimated to be US$ 45.8 billion under current eligibility, US$ 48.7 billion under WHO 2013 scenario and US$ 52.5 billion under the 90-90-90 scenario. The estimated funding gap for the six year period ranges between US$ 20 and US$ 25 billion. In this study, the costs of commodities were taken directly from data collated by other organisations.  No empirical cost estimates of service delivery were made.  Nor was there an attempt to understand the cost implications of the development synergies and social and programme enablers that may be needed to increase the number of people living with HIV knowing their status.  The new WHO recommendations need to be actively pursued if we are to meet targets, rather than passively continuing with “business as usual”. 

Nonetheless, the findings of this study highlight the gap between guidelines written by WHO and very real programmatic obstacles on the ground. There is evidence to suggest that universal test-and-treat strategies could lead to substantially improved health outcomes at the population level, as well as potentially being cost-saving in the long-term. However, as the authors have illustrated, it would require increased levels of funding. What needs to be explored further now is how to overcome the logistical hurdles of rolling out such an initiative. Changing systems and practices is costly and takes time. Health workers will have to be retrained, data collection strategies will have to be revised. Expanding treatment may also mean increasing the number of health staff working on this initiative, which has an opportunity cost that may reverberate in other parts of the health system. Substantially altering health service provision, particularly in weak health systems, may have knock-on effects with unexpected and unintended consequences.

WHO guidelines serve a vital purpose of giving us a goal to aim for. But studies like this one help us know if and how we can get there. 

Africa, Asia, Europe, Latin America, Oceania
Algeria, Angola, Armenia, Azerbaijan, Bahamas, Bangladesh, Barbados, Belarus, Belize, Benin, Bhutan, Bolivia, Botswana, Bulgaria, Burkina Faso, Burundi, Cambodia, Cameroon, Central African Republic, Chad, China, Comoros, Côte d'Ivoire, Cuba, Democratic Republic of the Congo, Djibouti, Dominican Republic, Egypt, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Georgia, Ghana, Guatemala, Guinea, Guinea-Bissau, Guyana, Haiti, Honduras, India, Indonesia, Iran (Islamic Republic of), Jamaica, Kazakhstan, Kenya, Kyrgyzstan, Lao People's Democratic Republic, Lesotho, Liberia, Madagascar, Malawi, Malaysia, Mali, Mauritania, Mauritius, Moldova, Mongolia, Morocco, Mozambique, Myanmar, Namibia, Nepal, Nicaragua, Niger, Nigeria, Pakistan, Papua New Guinea, Philippines, Republic of the Congo, Romania, Russia, Rwanda, Senegal, Serbia and Montenegro, Sierra Leone, Somalia, South Africa, Sri Lanka, Sudan, Suriname, Swaziland, Tajikistan, Thailand, Togo, Trinidad and Tobago, Tunisia, Uganda, Ukraine, United Republic of Tanzania, Uzbekistan, Viet Nam, Yemen, Zambia, Zimbabwe
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Vulnerabilities of children living with HIV positive adults

Children living with HIV-infected adults: estimates for 23 countries in sub-Saharan Africa.

Short SE, Goldberg RE. PLoS One. 2015 Nov 17; 10(11): e0142580.

Background: In sub-Saharan Africa many children live in extreme poverty and experience a burden of illness and disease that is disproportionately high. The emergence of HIV and AIDS has only exacerbated long-standing challenges to improving children's health in the region, with recent cohorts experiencing pediatric AIDS and high levels of orphan status, situations which are monitored globally and receive much policy and research attention. Children's health, however, can be affected also by living with HIV-infected adults, through associated exposure to infectious diseases and the diversion of household resources away from them. While long recognized, far less research has focused on characterizing this distinct and vulnerable population of HIV-affected children.

Methods: Using Demographic and Health Survey data from 23 countries collected between 2003 and 2011, we estimate the percentage of children living in a household with at least one HIV-infected adult. We assess overlaps with orphan status and investigate the relationship between children and the adults who are infected in their households.

Results: The population of children living in a household with at least one HIV-infected adult is substantial where HIV prevalence is high; in Southern Africa, the percentage exceeded 10% in all countries and reached as high as 36%. This population is largely distinct from the orphan population. Among children living in households with tested, HIV-infected adults, most live with parents, often mothers, who are infected; nonetheless, in most countries over 20% live in households with at least one infected adult who is not a parent.

Conclusion: Until new infections contract significantly, improvements in HIV/AIDS treatment suggest that the population of children living with HIV-infected adults will remain substantial. It is vital to on-going efforts to reduce childhood morbidity and mortality to consider whether current care and outreach sufficiently address the distinct vulnerabilities of these children.

Abstract Full-text [free] access

Editor’s notes: This paper is an important contribution to the literature on the impact of the HIV epidemic. Using Demographic and Health Survey (DHS) data from 23 countries it highlights the considerable number of children living with HIV-positive adults in sub-Saharan Africa. However, notable exceptions from the analysis (no DHS data available) included South Africa. This, coupled with specific issues related to DHS data collection methods and response rates, means that the number of children living with HIV-positive adults is much higher. Reductions in mortality from HIV due to increased treatment availability and the addition of adults newly acquiring HIV means that population of children living with an HIV-positive adult will continue to increase in the near future.

Children living with HIV-positive adults are clearly vulnerable and like all vulnerable children should be focussed on in efforts to promote child wellbeing. The authors suggest, however, that children living with HIV-positive adults may have distinct vulnerabilities that need to be considered. These include direct exposure to opportunistic infections, social stigma and disrupted networks, as well as increases in poverty. The challenge for many countries is how to identify these children and ensure that focussed programmes are delivered effectively.

Africa
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AIDS and bacterial disease remain leading causes of hospital admission

Causes of hospital admission among people living with HIV worldwide: a systematic review and meta-analysis.

Ford N, Shubber Z, Meintjes G, Grinsztejn B, Eholie S, Mills EJ, Davies MA, Vitoria M, Penazzato M, Nsanzimana S, Frigati L, O'Brien D, Ellman T, Ajose O, Calmy A, Doherty M. Lancet HIV. 2015 Oct;2(10):e438-44. doi: 10.1016/S2352-3018(15)00137-X. Epub 2015 Aug 11.

Background: Morbidity associated with HIV infection is poorly characterised, so we aimed to investigate the contribution of different comorbidities to hospital admission and in-hospital mortality in adults and children living with HIV worldwide.

Methods: Using a broad search strategy combining terms for hospital admission and HIV infection, we searched MEDLINE via PubMed, Embase, Web of Science, LILACS, AIM, IMEMR and WPIMR from inception to Jan 31, 2015, to identify studies reporting cause of hospital admission in people living with HIV. We focused on data reported after 2007, the period in which access to antiretroviral therapy started to become widespread. We estimated pooled proportions of hospital admissions and deaths per disease category by use of random-effects models. We stratified data by geographical region and age.

Findings: We obtained data from 106 cohorts, with reported causes of hospital admission for  313 006 adults and 6182 children living with HIV. For adults, AIDS-related illnesses (25 119 patients, 46%, 95% CI 40-53) and bacterial infections (14 034 patients, 31%, 20-42) were the leading causes of hospital admission. These two categories were the most common causes of hospital admission for adults in all geographical regions and the most common causes of mortality. Common region-specific causes of hospital admission included malnutrition and wasting, parasitic infections, and haematological disorders in the Africa region; respiratory disease, psychiatric disorders, renal disorders, cardiovascular disorders, and liver disease in Europe; haematological disorders in North America; and respiratory, neurological, digestive and liver-related conditions, viral infections, and drug toxicity in South and Central America. For children, AIDS-related illnesses (783 patients, 27%, 95% CI 19-34) and bacterial infections (1190 patients, 41%, 26-56) were the leading causes of hospital admission, followed by malnutrition and wasting, haematological disorders, and, in the African region, malaria. Mortality in individuals admitted to hospital was 20% (95% CI 18-23, 12 902 deaths) for adults and 14% (10-19, 643 deaths) for children.

Interpretation: This review shows the importance of prompt HIV diagnosis and treatment, and the need to reinforce existing recommendations to provide chemoprophylaxis and vaccination against major preventable infectious diseases to people living with HIV to reduce serious AIDS and non-AIDS morbidity.

Abstract access 

Editor’s notes: Despite the widening availability of antiretroviral therapy (ART), HIV-associated disease remains an important cause of illness and death. In this systematic review the authors summarise published data concerning causes of hospital admission among HIV-positive people since 2007. This date was selected on the basis that access to ART was limited prior to 2007.

Overall the most common causes of admission among adults, across all geographical regions, were AIDS-associated illness and bacterial infections. Tuberculosis was the most common cause among adults, accounting for 18% of all admissions, followed by bacterial pneumonia (15%). Among children, similarly AIDS-associated illnesses (particularly tuberculosis and Pneumocystis pneumonia) and bacterial infections were the most common causes of admission. Among the 20% of adults who died during their admission, the most common causes of death were tuberculosis, bacterial infections, cerebral toxoplasmosis and cryptococcal meningitis. Among children the most common causes of death were tuberculosis, bacterial infections and Pneumocystis pneumonia. Tuberculosis is likely to have been underestimated in these studies. Autopsy studies consistently illustrate that around half of HIV-positive people who have tuberculosis identified at autopsy had not been diagnosed prior to death.

The review highlights that the majority of severe HIV-associated disease remains attributable to advanced immunosuppression. This is reflected by a median CD4 count at admission among adults of 168 cells per µl. Some 30% of people first tested HIV positive at the time of the admission. The review underlines the need to promote HIV testing so that HIV-positive people can access ART, and prevent the complications of advanced HIV disease. It also underscores the need for better coverage of screening for tuberculosis and preventive therapy for people without active disease.  

Avoid TB deaths
Comorbidity, Epidemiology
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Switching to second-line ART – we need to do better

Monitoring and switching of first-line antiretroviral therapy in sub-Saharan Africa: collaborative analysis of adult treatment cohorts.

Haas AD, Keiser O, Balestre E, Brown S, Bissagnene E, Chimbetete C, Dabis F, Davies MA, Hoffmann CJ, Oyaro P, Parkes-Ratanshi R, Reynolds SJ, Sikazwe I, Wools-Kaloustian K, Zannou DM, Wandeler G, Egger M, for IeDea Southern Africa EA, West A. Lancet HIV. 2015 Jul 1;2(7):e271-e278.

Background: HIV-1 viral load testing is recommended to monitor antiretroviral therapy (ART) but is not universally available. The aim of our study was to assess monitoring of first-line ART and switching to second-line ART in sub-Saharan Africa.

Methods: We did a collaborative analysis of cohort studies from 16 countries in east Africa, southern Africa, and west Africa that participate in the international epidemiological database to evaluate AIDS (IeDEA). We included adults infected with HIV-1 who started combination ART between January, 2004, and January, 2013. We defined switching of ART as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to one including a protease inhibitor, with adjustment of one or more nucleoside reverse-transcriptase inhibitors (NRTIs). Virological and immunological failures were defined according to WHO criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% CIs comparing routine viral load monitoring, targeted viral load monitoring, CD4 monitoring, and clinical monitoring, adjusting for programme and individual characteristics.

Findings: Of 297 825 eligible patients, 10 352 (3%) switched to second-line ART during 782 412 person-years of follow-up. Compared with CD4 monitoring, hazard ratios for switching were 3·15 (95% CI 2·92–3·40) for routine viral load monitoring, 1·21 (1·13–1·30) for targeted viral load monitoring, and 0·49 (0·43–0·56) for clinical monitoring. Of 6450 patients with confirmed virological failure, 58·0% (95% CI 56·5–59·6) switched by 2 years, and of 15 892 patients with confirmed immunological failure, 19·3% (18·5–20·0) switched by 2 years. Of 10 352 patients who switched, evidence of treatment failure based on one CD4 count or viral load measurement ranged from 86 (32%) of 268 patients with clinical monitoring to 3754 (84%) of 4452 with targeted viral load monitoring. Median CD4 counts at switching were 215 cells per μL (IQR 117–335) with routine viral load monitoring, but were lower with other types of monitoring (range 114–133 cells per μL).

Interpretation: Overall, few patients switched to second-line ART and switching happened late in the absence of routine viral load monitoring. Switching was more common and happened earlier after initiation of ART with targeted or routine viral load testing.

Abstract access 

Editor’s notes: Routine viral load monitoring should allow the early identification of first-line antiretroviral therapy (ART) failure, allowing prompt switch to second-line ART. Prolongation of treatment with a failing regimen compromises future therapeutic options (through the accumulation of drug resistance mutations) and potentially leads to increased morbidity and mortality. Previous reports from Africa have suggested that surprisingly few people switch to second-line therapy, even in programmes with routine viral load monitoring. This raises concerns that there are challenges on the ground with identification and management of ART failure.

This is a comprehensive analysis bringing together data from a number of well-characterised cohorts in Africa. In this analysis, switching to second-line ART was rare (3% over an average of almost three years follow-up). In programmes with routine viral load monitoring, only half of the people with confirmed virologic failure on first-line ART (two viral loads >1000 copies/ml) were recorded as having been switched to second-line ART. Furthermore, half of the people that were switched to a second-line regimen did not have evidence of confirmed virologic failure, suggesting that some may have been switched too early without first attempting adherence programmes which may achieve re-suppression on first-line ART. Unsurprisingly, rates of switching were lower in programmes with CD4+ monitoring (with or without targeted viral load testing) or clinical monitoring alone. 

While guidelines and algorithms around identification and management of first-line ART failure are relatively clear and straightforward, translating this into action on the ground seems to be difficult. At least part of this is likely to be due to the lack of tools to reliably measure adherence and the consequent difficulty that frontline health care workers have in identifying people that truly require a switch to second-line ART. Moreover, most programmes still do not routinely monitor indicators relating to virologic suppression or treatment failure and so this might not be seen as a priority by health care workers and programme managers. There is a need for research to explore how best to maximise virologic suppression in resource-constrained settings, as well as studies to evaluate the impact of programmes such as point-of-care viral load testing.

Africa
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Expansions in HIV treatment believed to reduce HIV stigma

HIV treatment scale-up and HIV-related stigma in sub-Saharan Africa: a longitudinal cross-country analysis.

Chan BT, Tsai AC, Siedner MJ. Am J Public Health. 2015 Jun 11:e1-e7. [Epub ahead of print] doi:10.2105/AJPH.2015.302716

Objectives: We estimated the association between antiretroviral therapy (ART) uptake and HIV-related stigma at the population level in sub-Saharan Africa.

Methods: We examined trends in HIV-related stigma and ART coverage in sub-Saharan Africa during 2003 to 2013 using longitudinal, population-based data on ART coverage from the Joint United Nations Program on HIV/AIDS and on HIV-related stigma from the Demographic and Health Surveys and AIDS Indicator Surveys. We fitted 2 linear regression models with country fixed effects, with the percentage of men or women reporting HIV-related stigma as the dependent variable and the percentage of people living with HIV on ART as the explanatory variable.

Results: Eighteen countries in sub-Saharan Africa were included in our analysis. For each 1% increase in ART coverage, we observed a statistically significant decrease in the percentage of women (b = -0.226; P = .007; 95% confidence interval [CI] = -0.383, -0.070) and men (b = -0.281; P = .009; 95% CI = -0.480, -0.082) in the general population reporting HIV-related stigma.

Conclusions: An important benefit of ART scale-up may be the diminution of HIV-related stigma in the general population. .

Abstract access 

Editor’s notes: Focused on sub-Saharan Africa, this study suggests that a benefit of the scale-up of antiretroviral therapy (ART) may have been a reduction in HIV-associated stigma. The authors combine data on HIV-associated stigma from the Demographic and Health Surveys and AIDS Indicator Surveys with data on ART coverage from UNAIDS. The results are presented for each of 18 countries and the authors suggest that increases in ART coverage are correlated with decreasing stigma, especially among countries with high HIV prevalence. The authors hypothesise that by allowing a person with HIV to experience a healthier life, ART reduces the stigma of HIV’s association with moral deviance. The authors also attribute knowledge to decreases in stigma.

While addressing an interesting and important question, the paper has some limitations. We suggest that participant responses to questions about whether they would be willing to care for someone “sick with AIDS”, and whether they would want a family member to keep an AIDS diagnosis “secret” cannot safely be interpreted as reflecting stigmatising attitudes or anticipated stigma. It would have been interesting to know if the methods used in the analysis could assess the role of ART relative to other factors in being associated with any changes over time in HIV-associated stigma.

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Hepatitis B virus co-infection: a challenge to successful ART in sub-Saharan Africa?

Prevalence of HIV and hepatitis B virus co-infection in sub-Saharan Africa and the potential impact and program feasibility of hepatitis B surface antigen screening in resource-limited settings.

Stabinski L, OʼConnor S, Barnhart M, Kahn RJ, Hamm TE. J Acquir Immune Defic Syndr. 2015 Apr 15;68 Suppl 3:S274-85. doi: 10.1097/QAI.0000000000000496.

Background: Screening people living with HIV for hepatitis B virus (HBV) co-infection is recommended in resource-rich settings to optimize HIV antiretroviral therapy (ART) and mitigate HBV-related liver disease. This review examines the need, feasibility, and impact of screening for HBV in resource-limited settings (RLS).

Methods: We searched 6 databases to identify peer-reviewed publications between 2007 and 2013 addressing (1) HIV/HBV co-infection frequency in sub-Saharan Africa (SSA); (2) performance of hepatitis B surface antigen (HBsAg) rapid strip assays (RSAs) in RLS; (3) impact of HBV co-infection on morbidity, mortality, or liver disease progression; and/or (4) impact of HBV-suppressive antiretroviral medications as part of ART on at least one of 5 outcomes (mortality, morbidity, HIV transmission, retention in HIV care, or quality of life). We rated the quality of individual articles and summarized the body of evidence and expected impact of each intervention per outcome addressed.

Results: Of 3940 identified studies, 85 were included in the review: 55 addressed HIV/HBV co-infection frequency; 6 described HBsAg RSA performance; and 24 addressed the impact of HIV/HBV co-infection and ART. HIV/HBV frequency in sub-Saharan Africa varied from 0% to >28.4%. RSA performance in RLS showed good, although variable, sensitivity and specificity. Quality of studies ranged from strong to weak. Overall quality of evidence for the impact of HIV/HBV co-infection and ART on morbidity and mortality was fair and good to fair, respectively.

Conclusions: Combined, the body of evidence reviewed suggests that HBsAg screening among people living with HIV could have substantial impact on preventing morbidity and mortality among HIV/HBV co-infected individuals in RLS.

Abstract access 

Editor’s notes: The routes of transmission for hepatitis B virus (HBV) and HIV are the same, and they frequently co-infect individuals in high HIV prevalence settings. HIV has also been shown to accelerate the progression of HBV. This has important implications for ART programmes, given also the potential for hepatotoxicity of ART. The response of both infections to certain antivirals gives an opportunity to treat both infections simultaneously, but also the potential to engender resistant strains of virus if treatment is optimised for one and not the other.

This paper reviews the evidence that might support inclusion of HBV screening as part of HIV care programmes. No clinical trials have been done in this area, so the review is based on observational studies. The data are incomplete and geographically patchy, largely from Nigeria and South Africa. However, this does not prevent the authors from concluding that the co-infection risk is sufficiently high and the consequences of lack of treatment sufficiently severe to consider allocation of scarce resources to identify and manage HBV co-infection in HIV programmes. Appropriate validated screening tools - rapid tests for hepatitis B surface antigen - are available. The potential benefit warrants consideration of this issue in sub-Saharan Africa, and inclusion of HBV surveillance alongside HIV to resolve the paucity of data in most countries. This should be rapidly followed by further consideration of the cost- and risk-benefit of introduction of an HBV screening and treatment programme.

Interested readers might also refer to a review by Matthews et al. (J Clin Virol 2014;6:20-33) which considers similar questions and also discusses hepatitis C co-infection.

Avoid TB deaths
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Hepatitis B virus co-infection: a challenge to successful ART in sub-Saharan Africa?

Prevalence of HIV and hepatitis B virus co-infection in sub-Saharan Africa and the potential impact and program feasibility of hepatitis B surface antigen screening in resource-limited settings.

Stabinski L, OʼConnor S, Barnhart M, Kahn RJ, Hamm TE. J Acquir Immune Defic Syndr. 2015 Apr 15;68 Suppl 3:S274-85. doi: 10.1097/QAI.0000000000000496.

Background: Screening people living with HIV for hepatitis B virus (HBV) co-infection is recommended in resource-rich settings to optimize HIV antiretroviral therapy (ART) and mitigate HBV-related liver disease. This review examines the need, feasibility, and impact of screening for HBV in resource-limited settings (RLS).

Methods: We searched 6 databases to identify peer-reviewed publications between 2007 and 2013 addressing (1) HIV/HBV co-infection frequency in sub-Saharan Africa (SSA); (2) performance of hepatitis B surface antigen (HBsAg) rapid strip assays (RSAs) in RLS; (3) impact of HBV co-infection on morbidity, mortality, or liver disease progression; and/or (4) impact of HBV-suppressive antiretroviral medications as part of ART on at least one of 5 outcomes (mortality, morbidity, HIV transmission, retention in HIV care, or quality of life). We rated the quality of individual articles and summarized the body of evidence and expected impact of each intervention per outcome addressed.

Results: Of 3940 identified studies, 85 were included in the review: 55 addressed HIV/HBV co-infection frequency; 6 described HBsAg RSA performance; and 24 addressed the impact of HIV/HBV co-infection and ART. HIV/HBV frequency in sub-Saharan Africa varied from 0% to >28.4%. RSA performance in RLS showed good, although variable, sensitivity and specificity. Quality of studies ranged from strong to weak. Overall quality of evidence for the impact of HIV/HBV co-infection and ART on morbidity and mortality was fair and good to fair, respectively.

Conclusions: Combined, the body of evidence reviewed suggests that HBsAg screening among people living with HIV could have substantial impact on preventing morbidity and mortality among HIV/HBV co-infected individuals in RLS.

Abstract access 

Editor’s notes: The routes of transmission for hepatitis B virus (HBV) and HIV are the same, and they frequently co-infect individuals in high HIV prevalence settings. HIV has also been shown to accelerate the progression of HBV. This has important implications for ART programmes, given also the potential for hepatotoxicity of ART. The response of both infections to certain antivirals gives an opportunity to treat both infections simultaneously, but also the potential to engender resistant strains of virus if treatment is optimised for one and not the other.

This paper reviews the evidence that might support inclusion of HBV screening as part of HIV care programmes. No clinical trials have been done in this area, so the review is based on observational studies. The data are incomplete and geographically patchy, largely from Nigeria and South Africa. However, this does not prevent the authors to conclude that the co-infection risk is sufficiently high and the consequences of lack of treatment sufficiently severe to consider allocation of scarce resources to identify and manage HBV co-infection in HIV programmes. Appropriate validated screening tools such as rapid tests for hepatitis B surface antigen are available. The potential benefit warrants consideration of this issue in sub-Saharan Africa, and inclusion of HBV surveillance alongside HIV to resolve the paucity of data in most countries. This should be rapidly followed by further consideration of the cost- and risk-benefit of introduction of an HBV screening and treatment programme.

Interested readers might also refer to a review by Matthews et al. (J Clin Virol 2014;6:20-33) which considers similar questions and also discusses hepatitis C co-infection.

Avoid TB deaths
Africa
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