Wafaa El Sadr

Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration

BACKGROUND With the advent of effective antiretroviral treatment, the life expectancy for people with HIV is now approaching that seen in the general population. Consequently, the relative importance of other traditionally non-AIDS-related morbidities has increased. We investigated trends over time in all-cause mortality and for specific causes of death in people with HIV from 1999 to 2011. METHODS Individuals from the Data collection on Adverse events of anti-HIV Drugs (D:A:D) study were followed up from March, 1999, until death, loss to follow-up, or Feb 1, 2011, whichever occurred first. The D:A:D study is a collaboration of 11 cohort studies following HIV-1-positive individuals receiving care at 212 clinics in Europe, USA, and Australia. All fatal events were centrally validated at the D:A:D coordinating centre using coding causes of death in HIV (CoDe) methodology. We calculated relative rates using Poisson regression. FINDINGS 3909 of the 49,731 D:A:D study participants died during the 308,719 person-years of follow-up (crude incidence mortality rate, 12.7 per 1000 person-years [95% CI 12.3-13.1]). Leading underlying causes were: AIDS-related (1123 [29%] deaths), non-AIDS-defining cancers (590 [15%] deaths), liver disease (515 [13%] deaths), and cardiovascular disease (436 [11%] deaths). Rates of all-cause death per 1000 person-years decreased from 17.5 in 1999-2000 to 9.1 in 2009-11; we saw similar decreases in death rates per 1000 person-years over the same period for AIDS-related deaths (5.9 to 2.0), deaths from liver disease (2.7 to 0.9), and cardiovascular disease deaths (1.8 to 0.9). However, non-AIDS cancers increased slightly from 1.6 per 1000 person-years in 1999-2000 to 2.1 in 2009-11 (p=0.58). After adjustment for factors that changed over time, including CD4 cell count, we detected no decreases in AIDS-related death rates (relative rate for 2009-11 vs 1999-2000: 0.92 [0.70-1.22]). However, all-cause (0.72 [0.61-0.83]), liver disease (0.48 [0.32-0.74]), and cardiovascular disease (0.33 [0.20-0.53) death rates still decreased over time. The percentage of all deaths that were AIDS-related (87/256 [34%] in 1999-2000 and 141/627 [22%] in 2009-11) and liver-related (40/256 [16%] in 1999-2000 and 64/627 [10%] in 2009-11) decreased over time, whereas non-AIDS cancers increased (24/256 [9%] in 1999-2000 to 142/627 [23%] in 2009-11). INTERPRETATION Recent reductions in rates of AIDS-related deaths are linked with continued improvement in CD4 cell count. We hypothesise that the substantially reduced rates of liver disease and cardiovascular disease deaths over time could be explained by improved use of non-HIV-specific preventive interventions. Non-AIDS cancer is now the leading non-AIDS cause and without any evidence of improvement. FUNDING Oversight Committee for the Evaluation of Metabolic Complications of HAART, with representatives from academia, patient community, US Food and Drug Administration, European Medicines Agency and consortium of AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, ViiV Healthcare, Merck, Pfizer, F Hoffmann-La Roche, and Janssen Pharmaceuticals.

Program-level and contextual-level determinants of low-median CD4+ cell count in cohorts of persons initiating ART in eight sub-Saharan African countries.

Objective:In sub-Saharan Africa, many patients initiate antiretroviral therapy (ART) at CD4+ cell counts much lower than those recommended in national guidelines. We examined program-level and contextual-level factors associated with low median CD4+ cell count at ART initiation in populations initiating ART. Design:Multilevel analysis of aggregate and program-level service delivery data. Methods:We examined data on 1690 cohorts of patients initiating ART during 2004–2008 in eight sub-Saharan African countries. Cohorts with median CD4+ less than 111 cells/&mgr;l (the lowest quartile) were classified as having low median CD4+ cell count at ART initiation. Cohort information was combined with time-updated program-level data and subnational contextual-level data, and analyzed using multilevel models. Results:The 1690 cohorts had median CD4+ cell count of 136 cells/&mgr;l and included 121 504 patients initiating ART at 267 clinics. Program-level factors associated with low cohort median CD4+ cell count included urban setting [adjusted odds ratio (AOR) 2.1; 95% confidence interval (CI) 1.3–3.3], lower provider-to-patient ratio (AOR 2.2; 95% CI 1.3–4.0), no PMTCT program (AOR 3.6; 95% CI 1.0–12.8), outreach services for ART patients only vs. both pre-ART and ART patients (AOR 2.4; 95% CI 1.5–3.9), fewer vs. more adherence support services (AOR 1.6; 95% CI 1.0–2.5), and smaller cohort size (AOR 2.5; 95% CI 1.4–4.5). Contextual-level factors associated with low cohort median CD4+ cell count included initiating ART in areas where a lower proportion of the population heard of AIDS, tested for HIV recently, and a higher proportion believed ‘limiting themselves to one HIV-uninfected sexual partner reduces HIV risk’. Conclusion:Determinants of CD4+ cell count at ART initiation in populations initiating ART operate at multiple levels. Structural interventions targeting points upstream from ART initiation along the continuum from infection to diagnosis to care engagement are needed.

The Problem of Late ART Initiation in Sub-Saharan Africa: A Transient Aspect of Scale-up or a Long-term Phenomenon?

Efforts to scale-up HIV care and treatment have been successful at initiating large numbers of patients onto antiretroviral therapy (ART), although persistent challenges remain to optimizing scale-up effectiveness in both resource-rich and resource-limited settings. Among the most important are very high rates of ART initiation in the advanced stages of HIV disease, which in turn drive morbidity, mortality, and onward transmission of HIV. With a focus on sub-Saharan Africa, this review article presents a conceptual framework for a broader discussion of the persistent problem of late ART initiation, including a need for more focus on the upstream precursors (late HIV diagnosis and late enrollment into HIV care) and their determinants. Without additional research and identification of multilevel interventions that successfully promote earlier initiation of ART, the problem of late ART initiation will persist, significantly undermining the long-term impact of HIV care scale-up on reducing mortality and controlling the HIV epidemic.

Implementing antiretroviral therapy in resource-constrained settings: opportunities and challenges in integrating HIV and tuberculosis care

Highly active antiretroviral therapy (HAART) can transform the natural course of HIV infection by reducing morbidity and mortality as has been observed in many industrialized countries. The increasing availability of antiretroviral therapy through resources from among others the Global Fund to fight AIDS tuberculosis (TB) and malaria is a major step forward in the global effort to make HAART available in the developing world. There is therefore an urgent need to develop simple and sustainable strategies for initiation and delivery of HIV care and therapy to large numbers of patients in the context of the existing under-developed health care delivery systems. Among the various models of HIV care provision one proposed strategy is to integrate this care including HAART provision into the existing TB directly observed therapy (DOT) programs. This would allow for the opportunity to initiate HIV care and HAART for patients identified as HIV infected during TB treatment as well as to be able to continue such management for those who develop TB during HIV treatment. (excerpt)

Utility of Tuberculosis directly observed therapy programs as sites for access to and provision of antiretroviral therapy in resource-limited countries.

The overwhelming share of the global human immunodeficiency virus (HIV) infection and disease burden is borne by resource-limited countries. The explosive spread of HIV infection and growing burden of disease in these countries has intensified the need to find solutions to improved access to treatment for HIV infection. The epidemic of HIV infection and acquired immune deficiency syndrome (AIDS) has been accompanied by a severe epidemic of tuberculosis. Tuberculosis has become the major cause of morbidity and mortality in patients with HIV disease worldwide. Among the various models of provision of HIV/AIDS care, one logical but unexplored strategy is to integrate HIV/AIDS and tuberculosis care and treatment, including highly active antiretroviral therapy, through existing tuberculosis directly observed therapy programs. This strategy could address the related issues of inadequate access and infrastructure and need for enhanced adherence to medication and thereby potentially improve the outcome for both diseases.

Availability of nutritional support services in HIV care and treatment sites in sub-Saharan African countries.

OBJECTIVE To examine the availability of nutritional support services in HIV care and treatment sites across sub-Saharan Africa. DESIGN In 2008, we conducted a cross-sectional survey of sites providing antiretroviral therapy (ART) in nine sub-Saharan African countries. Outcomes included availability of: (i) nutritional counselling; (ii) micronutrient supplementation; (iii) treatment for severe malnutrition; and (iv) food rations. Associations with health system indicators were explored using bivariate and multivariate methods. SETTING Presidents Emergency Plan for AIDS Relief-supported HIV treatment and care sites across nine sub-Saharan African countries. SUBJECTS A total of 336 HIV care and treatment sites, serving 467 175 enrolled patients. RESULTS Of the sites under study, 303 (90 %) offered some form of nutritional support service. Nutritional counselling, micronutrient supplementation, treatment for severe acute malnutrition and food rations were available at 98 %, 64 %, 36 % and 31 % of sites, respectively. In multivariate analysis, secondary or tertiary care sites were more likely to offer nutritional counselling (adjusted OR (AOR): 2.2, 95 % CI 1.1, 4.5). Rural sites (AOR: 2.3, 95 % CI 1.4, 3.8) had increased odds of micronutrient supplementation availability. Sites providing ART for >2 years had higher odds of availability of treatment for severe malnutrition (AOR: 2.4, 95 % CI 1.4, 4.1). Sites providing ART for >2 years (AOR: 1.6, 95 % CI 1.3, 1.9) and rural sites (AOR: 2.4, 95 % CI 1.4, 4.4) had greater odds of food ration availability. CONCLUSIONS Availability of nutritional support services was high in this large sample of HIV care and treatment sites in sub-Saharan Africa. Further efforts are needed to determine the uptake, quality and effectiveness of these services and their impact on patient and programme outcomes.

Advanced disease at enrollment in HIV care in four sub-Saharan African countries: change from 2006 to 2011 and multilevel predictors in 2011.

Objectives:To examine changes between 2006 and 2011 in the proportion of HIV-positive patients newly enrolled in HIV care with advanced disease and the median CD4+ cell count at enrollment; and identify patient, facility, and contextual-level factors associated with late enrollment in care in 2011. Design:Cross-sectional over time. Methods:For time-trends analyses, routinely collected patient-level data (307 110 adults newly enrolled in 138 HIV clinical care facilities) in Kenya, Mozambique, Rwanda and Tanzania; and for analyses of correlates, patient-level data (46 201 in 195 facilities), and facility and population-level survey data were used. Late enrollment was defined as CD4+ cell count 350 cells/&mgr;l or less and/or WHO clinical stage 3/4. Results:Late enrollment declined from 69.9 to 57.2% (P < 0.0001); median CD4+ cell count increased from 242 to 292 cells/&mgr;l (Ptrend < 0.0001). In 2011, risk of late enrollment was significantly higher for men and nonpregnant women vs. pregnant women; patients aged above 25 vs. 15–25 years; nonmarried vs. married; and those entering from sites other than prevention of mother-to-child transmission. More extensive HIV testing coverage in the region of a facility was significantly associated with lower risk of late enrollment. Conclusions:Despite improvement, in 2011, 57% of patients entered HIV care who were already antiretroviral therapy-eligible. The lower risk of late enrollment among those referred from prevention of mother-to-child transmission and in regions where HIV testing coverage was higher suggests that innovative approaches to rapidly increase testing uptake among people living with HIV prior to the development of symptoms have the potential to reduce late enrollment in care.

HIV and people who use drugs in central Asia: confronting the perfect storm.

Despite substantial advances in reducing HIV incidence and expanding access to antiretroviral therapy (ART), Central Asia (CA) lags behind gains made in other countries (Joint United Nations Programme on HIV/AIDS, 2012a,b,c,d). While HIV incidence is decreasing globally, the number of new HIV infections in CA is rising among people who inject drugs (PWID), female sex partners of PWID, men who have sex with men (MSM), female sex workers (FSW), and migrant workers (Joint United Nations Programme on HIV/AIDS, 2012a,b,c,d; Donoghoe, 2012; Jolley et al., 2012; Thorne et al., 2010). In several CA countries (i.e., Kazakhstan, Kyrgyzstan, Uzbekistan, Tajikistan, Turkmenistan), an estimated 1% of adults inject drugs, but the number exceeds 10% in areas along major drug trafficking routes, representing one of the highest rates of injection drug use in the world (Joint United Nations Programme on HIV/AIDS, 2012a,b,c). More than half of recently-diagnosed HIV infections in the region are estimated to occur in the PWID population (Joint United Nations Programme on HIV/AIDS, 2012a,b,c). Furthermore, the prevalence of hepatitis C virus (HCV) infection is exceptionally high among PWID in these countries (Beyrer et al., 2009; Walsh and Maher, 2012; El-Bassel et al., 2013), and the rates of multidrug-resistant tuberculosis (MDR-TB) in PWID in CA are also among the highest in the world (World Health Organization, 2012). Recent evidence suggests that PWID in CA are increasingly using heroin synthetic substitutes and mixing different drugs and alcohol, which may further increase their risk for morbidity and mortality from HIV, HCV, TB, and overdose. Some forms of non-injection substance use, particularly amphetamine-type stimulants and other drugs such as “krokodil” (a home-made drug) have increased in CA (Grund et al., 2013). Excessive alcohol use in the region is associated with decreased utilization of health services, poor adherence to ART (Mellins et al., 2009), and engagement in risky drug-related and sexual behaviors among PWID (Wolfe et al., 2010; Abdala et al., 2010). Excessive alcohol intake among individuals receiving ART is also associated with a decreased likelihood of them having an undetectable HIV viral load (Gonzalez et al., 2013). The relationship between non-injection drug use and HIV acquisition among PWID in the region remains poorly understood. Despite evidence suggesting widespread drug use (injection and non-injection) and the rising incidence of HIV among PWID in CA, region-specific research and scientific publications remain limited on the epidemiology of HIV and its co-morbidities, as well as HIV prevention and treatment among PWID. In this supplement of Drug and Alcohol Dependence, authors from diverse disciplinary backgrounds and differing scientific expertise seek to address these large gaps in the scientific literature. This supplement is designed to deepen understanding of the HIV epidemic’s scope, the scope of related co-morbidities such HCV and TB in CA, and the status of harm reduction and other HIV-related services. Given recent advances in biomedical HIV treatment and bio-behavioral prevention, this supplement highlights the need for implementing such interventions in the region and emphasizes the importance of promoting prevention and health care for PWID in CA. Each of the articles in this supplement describes available information on a specific issue, identifies gaps in scientific knowledge, and provides an agenda for future research endeavors. Although this supplement issue focuses mainly on the five countries traditionally considered to constitute the Central Asia region (Kazakhstan, Kyrgyzstan, Uzbekistan, Tajikistan, Turkmenistan), a number of the included papers provide information on relevant issues from adjacent countries with similar epidemics, countries such as Afghanistan, Mongolia, and China. 1.1. Structure of the supplement The first section of this supplement focuses on the epidemiology of HIV and the overlapping co-morbidities of HCV and TB, and describes risk environments that increase the risk of HIV among key populations in CA: PWID, MSM, female sex workers, and migrant workers. The second section focuses on the scope of harm reduction programs in CA, including policies and socio-structural barriers that prevent PWID from accessing and utilizing such programs. This section also addresses overdose prevention and access to naloxone. The third section focuses on the status of HIV testing and HIV care and treatment, and discusses coverage of biomedical prevention among PWID in this region.

Improving pathology and laboratory medicine in low-income and middle-income countries: roadmap to solutions

Insufficient awareness of the centrality of pathology and laboratory medicine (PALM) to a functioning health-care system at policy and governmental level, with the resultant inadequate investment, has meant that efforts to enhance PALM in low-income and middle-income countries have been local, fragmented, and mostly unsustainable. Responding to the four major barriers in PALM service delivery that were identified in the first paper of this Series (workforce, infrastructure, education and training, and quality assurance), this second paper identifies potential solutions that can be applied in low-income and middle-income countries (LMICs). Increasing and retaining a quality PALM workforce requires access to mentorship and continuing professional development, task sharing, and the development of short-term visitor programmes. Opportunities to enhance the training of pathologists and allied PALM personnel by increasing and improving education provision must be explored and implemented. PALM infrastructure must be strengthened by addressing supply chain barriers, and ensuring laboratory information systems are in place. New technologies, including telepathology and point-of-care testing, can have a substantial role in PALM service delivery, if used appropriately. We emphasise the crucial importance of maintaining PALM quality and posit that all laboratories in LMICs should participate in quality assurance and accreditation programmes. A potential role for public-private partnerships in filling PALM services gaps should also be investigated. Finally, to deliver these solutions and ensure equitable access to essential services in LMICs, we propose a PALM package focused on these countries, integrated within a nationally tiered laboratory system, as part of an overarching national laboratory strategic plan.

Strengthening the Quality and Quantity of the Nursing and Midwifery Workforce: Report on Eight Years of the NEPI Project

In response to the urgent need to scale up access to antiretroviral therapy, the Global Nursing Education Partnership Initiative (GNCBP), a PEPFAR program administered by the U.S. Department of Health Resources and Services Administration (HRSA), was implemented from 2011 to 2018 by ICAP at Columbia University. Working closely together, HRSA and ICAP partnered with local nursing leaders and ministries of health to strengthen the nursing and midwifery workforce across 11 countries. This multi-country project, developed to address critical gaps in nursing education and training worked across six building blocks of health workforce strengthening: infrastructure improvement, curricula revision, clinical skills development, in-service training, faculty development and building partnerships for policy and regulation to increase the quality and quantity of the nursing and midwifery workforce. As a result, 13,387 nursing and midwifery students graduated from schools supported under GNCBP. A total of 5,554 nurses received critical in-service training and 4,886 faculty, clinical mentors and preceptors received training in key clinical care areas and modern teaching methodologies. ICAP completed 43 infrastructure enhancements to ensure environments conducive to learning and strengthened nursing leaders as best evidenced by the election and formation of Mozambique’s first national nursing council and the NEPI Network. Going forward, efforts to strengthen nursing and midwifery can build on the results of the GNCBP project. Going forward, a new group of African nursing leaders are being supported to advocate for high quality patient-care led through inter-professional collaboration and participation in international efforts championing the critical role of nurses in achieving universal health coverage.