More information on causes of death needed to fine-tune ART services in Africa
Knowing the causes of death as well as mortality rates among patients on antiretroviral therapy in Rwanda may help improve service delivery, Innocent Turate and colleagues reported in a study presented at the HIV Implementers’ Meeting in Namibia last month.
Loss of patients to follow-up continues to be a significant problem for treatment programmes in many parts of Africa, but measures to improve patient retention in care require a better understanding of why patients are lost to follow-up, and in particular, the number of deaths and the causes of death among those who start treatment.
A retrospective analysis from 2003 to 2008 was undertaken and included a chart review of 11,785 patients on antiretroviral therapy (ART) in 29 Family Health International (FHI)-supported sites in Rwanda, where Family Health International is involved in the delivery of treatment and care funded by the US PEPFAR programme.
During the period under review 592 patients died (5.8% of all those treated). The cause of death was determined by medical file and chart review and post-mortem interview with relatives. Data collected included date of starting ART, baseline CD4 count, baseline WHO clinical stage, cause of death if known and place of death (home, health centre, hospital).
With increased coverage (from two sites in 2003 to 29 in 2008) the number of deaths appears to have stabilised at around 150 for each of the last three years, whereas the numbers lost to follow-up increased from three in 2003 to 143 in 2008.
The median time between beginning ART and death was two months. Death registration forms with additional information were available for 73.3% (434). Of these, close to half died at home with CD4 counts available for over 90%. Just under 80% of those had CD4 counts below 200 cells/mm³ (the median was 109 cells/mm³) at the time of treatment initation, compared to 52.4% for all ART patients. The vast majority (83%) were identified as having WHO clinical stage 3 or 4 HIV disease at baseline.
Cause of death was determined for 66.4%. The most frequent known cause of death was tuberculosis and non-tuberculosis confirmed pulmonary disease (28%) followed by chronic diarrhoea at 8.5%. Eighty per cent of all deaths with unknown causes occurred at home.
Close to 80% of patients died within the first six months of starting treatment and death was strongly associated with a low CD4 count.
The death rate of 5.8% is similar to rates seen in Europe and North America. In contrast to such high-income countries non-HIV-related causes of death, for example, cardiovascular disease and diabetes, drug-related toxicity and cancers did not appear to be a major cause of death in Rwanda.
Limitations of the study cited by the author include the retrospective nature of a study that relied on a recording and reporting system that lacked codification and classification of causes of death, and the absence of documentation for the high proportion of deaths that occurred in the home.
The authors suggest that in light of the number of deaths due to non-TB confirmed pulmonary disease, and the high proportion of patients with low CD4 counts, an Immune Reconstitution Inflammatory Syndrome (IRIS) diagnosis is relevant and recommend strengthening clinician skills enabling them to identify and manage IRIS as well as other critical conditions in patients with low CD4 counts.
With TB identified as the leading cause of death, maintenance and reinforcement of the integration of TB/HIV activities was also recommended. In addition, strategies are required to enable earlier initiation of ART and intensive follow-up of those with low CD4 counts to help address unknown causes of death as well as improve service delivery (FHI has just implemented a new strategy for the latter called Acuity Case Management).
With increased life expectancy due to ART, assessment of non-AIDS defining diseases is suggested. The authors also recommended that the Ministry of Health consider making the systematic reporting of causes of death standard policy at the health facility level, together with the institution of a national death registry.
Reference
Turate I et al. Causes of death in HIV-infected patients receiving HAART in Rwanda. HIV Implementers' Meeting, Windhoek, Namibia, abstract 1793, June 2009.
'Know your CD4' campaign improves knowledge of HIV status, treatment initiation in Tanzania
A large-scale drive to improve knowledge of CD4 cell counts among people receiving HIV care in a Tanzanian district resulted in increased uptake of CD4 testing, an increase in treatment initiation and an improvement in patient retention, Tanzanian researchers reported at the HIV Implementers’ meeting last month in Namibia.
Late initiation of treatment remains a major challenge in developing countries, despite a WHO recommendation that treatment should be initiated before the CD4 cell count falls below 200 wherever CD4 counting is available and resources permit.
Treatment providers in Tanzania identified lack of CD4 testing and lack of knowledge of CD4 count by clinicians and patients as a barrier to timely initiation of treatment, and developed an intervention to improve the use of CD4 counts in clinical decision-making and raise awareness of the value of knowing one’s CD4 count among patients.
AIDSRelief Tanzania launched a “Know Your CD4 Campaign” to counter the absence of CD4 counts. Treatment providers estimated that around 3,000 people eligible for treatment were not on treatment. These were the target population for the campaign.
The campaign took place over a period of three weeks in the Tanga Region which has nine hospitals, 12 health centres and three CD4-counting machines. Eighteen sites were covered and three additional CD4 counting machines provided.
The organisation comprised 17 people (nurses, adherence support, and pharmacy (two staff); Laboratory (two staff); Doctors (5); Programme staff (4) and community-based health workers (4)). The primary objectives were to improve clinical systems and care; improve staff education and training (emphasising national guidelines that require CD4 counts, laboratory testing and staging), and increase patient ownership with an emphasis on participation in their own healthcare.
The campaign consisted of a multi-disciplinary approach to address the challenges:
- Triaging – a patient was sent for CD4 count if it was not in their chart
- Pharmacy – assurance of adequate drugs on-site to treat newly identified, eligible people.
- Community mobilisation efforts included sensitisation campaigns with a focus on stigma reduction and the importance of disclosure; understanding what a CD4 count meant and encouragement to request testing; promotional t-shirts and pens; training people living with HIV and community volunteers as CD4 ambassadors (a buddy system); health education sessions in clinic; support group meetings.
- Distribution of brochures at VCT/TB centers emphasising the importance of referring HIV-positive patients to a clinic for follow-up and staging.
- Clinic staff were re-educated on the importance of CD4 counts.
- Laboratory: Inventory of laboratory equipment; revised laboratory policies and procedures including joint meetings between laboratory personnel and administration to educate them about procedures. Coordination meetings at each hospital and among all hospitals took place at which the daily capacity of the CD4-counting machine was discussed, the number of samples per site was quantified, and planning for the best utilisation of available laboratory capacity and sample transportation was discussed, with the allocation of specific days on which particular sites would send samples.
- Better communication with the laboratories and flagging of patient files alerted clinicians to the availability of CD4 results.
Outcomes included improved flow of patients through the clinic. Regular meetings between Care and Treatment Clinic staff with laboratory personnel improved communication and teamwork. Patients became more knowledgeable about their care, and the introduction of a buddy system served to reinforce patient involvement in their own care.
Within the laboratories instruments were used to maximum capacity, specimen handling improved and the number of specimens from each site increased. Cooperation among laboratory staff from different sites also improved.
The number of CD4 samples increased by 114% from May (3,585 samples) to October 2007 (7,698 samples). Test results prior to the campaign took two to three days, whereas now results are received on the same day. Patient retention increased from 69% in December 2007 to 72% in February 2008. ART enrollment increased by 62% between June and September 2007.
The campaign resulted in clinicians beginning ART earlier and more closely monitoring their patients who in turn were more involved and knowledgeable about their own care. The number of CD4 tests and people on ART increased considerably. The CD4 campaign has been replicated successfully in Zambia and Kenya.
Next steps include looking at the referral system and the network of support to improve adherence support programmes as well as better integration with other services such as TB, prevention of mother to child transmission and voluntary counselling and testing; and improved use of data.
Reference
Aidi M et al. Know your CD4 Campaign: an approach to increase numbers of people on treatment and enhancing patient empowerment. HIV Implementers' Meeting, Windhoek, Namibia, abstract 1318, June 2009.
Scale up of early infant diagnosis in rural Ethiopia successful
Establishing and scaling up early infant HIV diagnosis (EID) programmes is feasible in even the most remote parts of Ethiopia, reported Berhanu Gudetta and colleagues in a study at the HIV Implementers’ Meeting, held in Windhoek, Namibia in early June.
Renovation of two regional laboratories making DNA PCR testing possible, coupled with the successful use of dried blood spot (sometimes referred to as DBS increased the numbers of infants receiving early diagnosis and consequently improved early initiation of antiretroviral therapy (ART) for infants aged 0-18 months.
The 2008 WHO guidelines recommend all infants infected with HIV under 12 months of age begin ART. Without ART 50% of children with HIV will die before the age of two. HIV DNA testing is necessary to make a definitive diagnosis in children below 18 months due to the persistence of maternal antibodies up until this age. The use of dried blood spots has simplified sample collection as it is less invasive in infants and facilitates storage and transportation to laboratories equipped to carry out DNA testing using polymerase chain reaction (PCR) testing.
Ethiopia has an estimated 1.7 million people infected with HIV, approximately 80% of whom live in rural areas. Free antiretroviral treatment began to be provided in 2005. Currently 20,522 children are estimated to be in need of ART while 7,399 are on treatment.
Johns Hopkins University Technical Support for the Ethiopian ART Initiative (JHU TSEHAI) is funded by PEPFAR-Ethiopia to provide technical assistance to 20 ART hospitals with the aim of eventually doubling this number. Currently JHU TSEHAI supports 55 ART sites and 70 PMTCT sites across four regions in Ethiopia serving approximately 19.3 million (total population 77 million).
Challenges common to other resource poor countries included: limited access to early infant diagnosis; a lack of trained staff; no sample collection, transportation and storage system; a lack of dried blood spot and DNA PCR supplies; no linkage for HIV-infected infants to ART clinics, and a limited number of laboratories capable of performing DNA PCR.
In January 2006 JHU TSEHAI supported the start up of EID programmes in five hospitals in Addis Ababa. Prior to scale up at the end of January 2008 692 infants had been tested with DNA PCR.
As part of the national plan to scale up EID programmes JHU TSEHAI in collaboration with the Centers for Disease Control and Prevention (CDC)-Ethiopia, EHNRI (Ethiopian National Laboratories), the Clinton HIV/AIDS Initiative (CHAI) and the regional laboratory staff renovated two laboratories, one in the capital (Addis Ababa) and one in the South (Hawassa), to perform HIV DNA PCR testing.
The national laboratory programme owns and maintains the two laboratories. Johns Hopkins University together with its partners supported the establishment of the following systems: dried blood spot collection and storage; sample referrals for surrounding hospitals and health centres; laboratory standard operating procedures and guidelines; and on-site training.
Dried blood spot samples were transported by laboratory courier service in Addis Ababa and by clinical mentors in remote areas. Future plans are to send dried blood spots through intra-Ethiopian priority mail.
Infants from PMTCT and ART clinics were tested as per the national algorithm for infant diagnosis. Samples were collected and transported weekly to the national laboratory and the regional laboratories for DNA PCR testing and results were then sent back to each hospital.
An analysis for the period from December 2006 until April 2009 (using fiscal years) reviewed infant age at sample collection, results of DNA PCR testing, turnaround time, EID coverage and changes in PMTCT regimens.
By January 2009 EID programmes had begun in 58 hospitals and 23 health centres. Health workers trained on dried blood spot sample collection and early infant diagnosis protocols increased by 300% (from 85 to 257). The number of infants tested almost doubled (from 692 to 1340). Dried blood spots were used to test all infants referred from PMTCT and ART clinics over six weeks of age and below 12 months and at some sites all aged below 18 months.
Changes in PMTCT regimens from single dose nevirapine to combined prophylaxis for mother and infants happened over the period under review and resulted in a decreased HIV DNA-positive rate, from 19.7% in 2006 to 11.5% in 2007 and 10.9% in 2008 (seven months of data).
HIV DNA-positive rates varied by age: 0-6 month age group 12.6% (65 infants); 6-12 month age group 29.8% (39) and for those over 12 months of age, 33.3% (7). Average turnaround time was two to four weeks. Testing of older children was due to testing of symptomatic children early in the programme.
Successful scale up of EID programmes depended upon partnerships between government institutions and external partners with specific and complementary areas of expertise. DBS enabled infants in remote areas to access DNA PCR (EID) services. The authors conclude that “successful use of DBS will optimize early infant diagnosis, thus increasing ART use in infants and decreasing overall morbidity and mortality”.
Reference
Gudetta B et al. EID scale-up and partnership with regional laboratories for sustainability. HIV Implementers' Meeting Windhoek, Namibia, abstract 1286, June 2009
High Risk Express Care reduces mortality, improves retention in Kenya
Nurse-based rapid assessment clinics in Western Kenya may improve survival and clinical retention of very sick patients beginning combination antiretroviral therapy (ART), Paula Braitstein and colleagues reported at the HIV Implementers' Meeting in Namibia last month.
Launched in 2001 the USAID-Academic Model Providing Access to Healthcare (AMPATH) has provided services to over 90,000 men, women and children with HIV in 18 parent and 10 satellite clinics in urban and rural areas throughout Western Kenya.
High Risk Express Care began as a pilot project in March 2007 in four high-volume clinics. Reducing mortality and loss to follow up in HIV-infected adults with CD4 counts below 100 cells/mm³ when beginning ART, as well as increasing clinic capacity without additional costs, were the primary goals.
By June 2008 the project had been rolled out to 18 clinics.
Routine care for patients beginning ART involves a clinical officer seeing the patient at every visit and prescribing ART. Monthly visits are scheduled unless clinical indications determine otherwise.
High Risk Express Care for patients beginning cART involves a clinical officer seeing the patient and prescribing ART. The patient is then referred to Express Care (EC) upon ART initiation. The clinical officer will see the patient on a monthly basis. In the interim weeks over a period of three months a nurse will either see the patient in the clinic or talk to them over the phone. Vital signs are taken and a rapid symptom assessment is done each time, with immediate referral to a clinical officer if symptoms call for it.
To assess the comparative impact of High Risk Express Care and routine care on clinical outcomes a retrospective observational study was undertaken. Criteria for inclusion included: beginning ART, having a CD4 count below 100 cells/mm³ and being 14 years of age and over. Endpoints were mortality and loss to follow up defined as absent from the clinic for at least 3 months without evidence of patient death.
Over a period of 10.5 months (March 1, 2007 and January 15, 2008) 2601 patients with a CD4 count below 100 began cART. A total of 14 out of the 28 clinics had begun HREC with a corresponding total of 378 (14.5%) eligible patients enrolled. Median cell count at initiation for the routine care group was 44, compared with 47 in the HREC group. The probability of remaining alive after 300 days was 95% for those in express Care and 91% for those in routine care. The probability of remaining alive and in care after 300 days was 86% for those in express care and 75% for those in routine care. In both cases the results were statistically significant.
Concern over selection bias in terms of clinics and patients selected for express care, use of cotrimoxazole (Septrin) and provider bias regarding adherence to protocols prompted the researchers to perform a sub-analysis which was restricted to clinics which had initiated express care. Eligibility criteria for patients in this sub-analysis included: initiation of ART after express care was initiated in the clinic and being eligible for express care (a CD4 count of ≤100 cells/mm³).
A total of 715 patients were included, 336 (46.9%) in express care and 379 (53.1%) in routine care. A lower proportion was on TB treatment and a higher proportion attended urban clinics than in the initial analysis. 98% (EC) versus 91% (RC) were using cotrimoxazole at initiation of cART.
Ninety-six per cent of patients in express care and 89/90% in RC were alive after 300 days; 85% in EC and 76% in RC were alive and in care after 300 days. Adjustment for all factors (gender, age, CD4 at cArt initiation, treatment for tuberculosis at cART initiation, clinic, use of cotrimoxazole or dapsone at ART initiation, WHO clinical stage at ART initiation, and time taken to get to clinic) showed a 60% decrease in mortality for those in EC. Adjustment for the same factors indicated that those in express care were half as likely to become lost to follow up (AHR 0.45, 95% CI:0.27-0.77).
Those in express care were seen by a dedicated nurse team at the clinic, helping ease clinic congestion. No cost-effectiveness analysis was undertaken.
The authors note that study limitations include the fact that the data are observational, and determination of outcomes is incomplete. They also note that just because clinical protocols exist, they may not be fully implemented, which could lead to an underestimate of the impact of express care when fully implemented.. Adherence to other protocols, for example cotrimoxazole prophylaxis, may also affect outcomes.
High risk express care appears to improve clinical retention and reduces mortality, but there is uncertainty as to whether outcomes are due to early identification, improved adherence or the dedication of nurses.
Paula Braitstein of AMPATH said that paying close attention and dealing with issues rapidly contributed to the outcomes. Symptoms were identified within days, adherence barriers readily identified, and referral took place immediately when problems arose. No shows are followed-up, and there is an active outreach programme led by HIV-positive people. In this specific setting nurses were underutilised, she noted, so their time so could be dedicated to express care, and consequently their workload was not affected, but this is not the norm in Kenya. She concluded that this model of care is “possibly generalisable and intuitively makes sense”.
Reference
Braitstein, P et al. High Risk Express Care: a novel care model to reduce early mortality among high risk HIV-infected patients initiating combination antiretroviral treatment. HIV Implementers’ Meeting, Namibia, abstract 1556, June 2009.
Family-centred approach improves uptake of testing and care in Rwanda
A family-centered approach tailored to children’s needs in Rwanda increased the number of children receiving HIV, testing care and treatment according to findings presented at the HIV Implementers Meeting held in Namibia in June.
In October2007 Intrahealth’s HIV/AIDS Clinical Service Program (HCSP) began training providers in family-centered counselling and testing (CT) at 14 of their sites. The target population was families of women identified as HIV-positive during antenatal care. Counselling and testing sessions were held on weekends and holidays and all families in the area were invited so as not to draw attention to or stigmatise the target population. Children were invited through youth groups to ensure confidentiality.
Prior to the initiation of the programme 3,000 children had been tested. At the end of the first year of the programme (September 2008) there was a sevenfold increase in children tested, to more than 22,000. In the rural areas there was a doubling of numbers of children tested.
Before the programme began children represented 9% of all HIV-tested individuals in HCSP’s sites and at the end of the first year of the programme this increased to 30% (16,494). Of the 1,371 HIV-positive clients identified 134 (9.8%) were children. The HIV prevalence rate in Rwanda is 3%.
Comparison of sites at the end of the first year showed considerable variation. At Mukono and Gisika, children represented 55% and 51% of all tested clients, with 10.7% (11) and 29.2% (7) respectively identified as HIV positive. At Rwesero and Tanda children represented 42.4% and 27.8% of all tested clients with 18.6% (15) and 2.3% (1) respectively identified as HIV positive, while at Rokomo children represented 23.4% of all tested clients of which 8.4% (24) were children.
Children who tested positive were immediately enrolled on treatment. Health care facilities managed their own funds through sub-grants that gave them the necessary freedom to run and manage weekend clinic sessions in collaboration with the local community. Services for the entire family are thus provided in a single visit reducing costs and facilitating care and treatment.
Challenges included the difficulty of following up children identified as HIV-positive once they returned to school; clarification of parents’ roles and providing adequate information for the care of their HIV-positive children, as well as the fears parents expressed for their children and their ability to cope.
Testing and counselling programmes that are tailored to the specific needs of children within a family-centered approach will allay fears and contribute to identifying children who are HIV- positive leading to earlier (and more effective) treatment and care, the study researchers concluded
Reference
Ngendahimana G. et al. Promoting a family-centered approach in scaling-up treatment services for children in Rwanda. HIV Implementers’ Meeting, Namibia, abstract 1049, June 2009.