The shortage of healthcare workers is one of the major obstacles to the scale-up of antiretroviral therapy (ART), especially in sub-Saharan Africa where two-thirds of the world's 34 million HIV-infected people reside.1–3 The lack of physicians is the most critical issue with major consequences on treatment expansion as physician-initiated and monitored ART is the international reference model of care.4,5 The situation is not expected to improve in the near future as 32 African countries will not meet the required number of physicians to cover their needs by 2015.6 Personnel shortages are most acute in rural areas where ART is now decentralized, in accordance with the World Health Organization's (WHO) public health approach.7
One of the solutions promoted by the WHO to overcome this shortage is task shifting, that is to say the transfer of HIV care from physicians to nonphysician clinicians, nurses, or community health workers.4,8 This strategy is already used successfully for other health interventions in many settings in African and industrialized countries alike (eg, the United States, the United Kingdom, and Australia). It is worth noting that task shifting for ART is less common in French-speaking Western and Central African countries than in English-speaking Eastern and Southern African countries. Moreover, nonphysician clinicians are quite rare in the former and, when such task shifting is used, it is mainly nurse-based (as is the case for task shifting in other domains of health).9
A number of Eastern and Southern African programs adopting the strategy of task shifting to nurses have reported favorable but limited data on patient outcomes.10–17 Recently, 2 trials in South Africa Comprehensive International Program for Research in AIDS in South Africa [CIPRA-SA] and Streamlining Tasks and Roles to Expand Treatment and Care for HIV [STRETCH] have demonstrated the effectiveness of nurse-monitored ART as compared with physician-monitored ART.18,19 In our study, we assessed the effectiveness of task shifting from physicians to nurses for ART in terms of HIV virological success, immunological recovery, mortality, and disease progression to death or to WHO clinical stage 4, using data from the Stratall ANRS/ESTHER trial in rural district hospitals in Cameroon.
This cohort study was performed between May 2006 and April 2010. The Stratall randomized trial was initially designed to compare the effectiveness and safety of a laboratory plus clinical monitoring strategy for ART (including HIV viral load and CD4 cell count), entitled LAB, with a strategy using clinical monitoring alone, entitled CLIN. The trial's methods and main results have been described extensively elsewhere.20 Briefly, 459 ART-naive patients were recruited in 9 district hospitals in Cameroon and followed up for 24 months after ART initiation by hospital healthcare workers. Patients were considered eligible if they were 18 years or older and had confirmed HIV-1 group M infection and WHO clinical stage 3 or 4 or WHO clinical stage 2 with a total lymphocyte count of <1200 cells per microliter. The protocol was approved by the National Ethics Committee of Cameroon and the Institutional Ethics Committee of the French Institut de Recherche pour le Développement. All the patients gave their written informed consent.
Clinical visits including an interview and a physical examination were scheduled at weeks 0 and 2, months 1 and 3, and every 3 months thereafter. At week 2 and months 3, 9, 15, and 21, nurses assessed patients in the CLIN group and, in the case of adverse events, referred them to physicians for care. Systematic appointments with physicians were scheduled for all other visits. The patients in the LAB group were supposed to be seen by physicians for all study visits. In practice however, the patients in both groups were sometimes visited by nurses instead of the scheduled physician and, in the CLIN group, physicians sometimes performed visits scheduled for nurses. This situation arose because of the temporary unavailability of physicians, less than optimal local organization and potential intergroup contamination. The patients who did not attend scheduled appointments were telephoned or visited at home. The patients could also attend clinics whenever they felt unwell. Clinical staging of HIV disease was based on the 2006 revised WHO classification.21 CD4 cell count (FACSCount device, Becton Dickinson, Mountain View, CA) and plasma viral load (RealTime HIV-1 assay, Abbott Molecular, Des Plaines, IL) were assessed at baseline and every 6 months thereafter.
Data from the CLIN and LAB groups were pooled for the present analysis because they did not differ in terms of patient characteristics or outcomes.20 To assess the effectiveness of task shifting from physicians to nurses, a consultant ratio was calculated for each patient at each follow-up time point. More precisely, the consultant ratio was constructed as the total number of visits made by nurses divided by the total number of visits made by physicians from recruitment to a given visit for each patient. Thus, the consultant ratio increased simultaneously to the number of visits made by nurses. For instance, if a patient was seen by a physician at the first and third visits and by a nurse at the second visit, then the consultant ratio at the third visit was 0.5 (ie, 1/2). By contrast, if a patient was always seen by a physician at all 3 visits, then the consultant ratio was 0 (ie, 0/3). If a visit was carried out jointly by a nurse and a physician, the consultant ratio remained unchanged with regard to the previous visit. Because the consultant seen at any given visit could not influence patient outcomes during that same visit (HIV virological success, CD4 recovery, death, or the presence of a new or recurrent WHO clinical stage 4 adverse event), the consultant ratio at the previous visit was therefore considered.
Virological success (<40 copies per milliliter) was assessed using mixed logistic regressions, whereas CD4 cell count evolution from ART initiation was assessed using mixed linear regressions. Because Schoenfeld residuals in Cox analyses rejected the proportional hazards hypothesis for important covariates (eg, consultant ratio), survival analyses (mortality on the one hand and disease progression to death or to a WHO clinical stage 4 adverse event on the other) were conducted using accelerated failure time models based on the lognormal distribution. The association between the presence of an adverse event and the type of consultant seen at a given visit was investigated using a mixed logistic regression model. Lastly, losses to follow-up were assessed using a binomial generalized estimating equations model.
Multivariate analyses were systematically adjusted for gender (women versus men), baseline age (≥35 versus <35 years), baseline CD4 cell count (≤200, 201–350 and >350 cells per microliter), and baseline HIV viral load (continuous variable). They were also adjusted for the following baseline covariates when associated with a conservative P value of <0.25 in the univariate analysis: body mass index (>18 versus ≤18 kg/m2), WHO clinical stage (stage 4 versus stage 2 or 3), hemoglobin level (>10 versus ≤10 g/dL), and the monitoring strategy (CLIN versus LAB). A backward elimination procedure was used to determine the final model containing only the consultant ratio, gender, age, CD4 cell count, and HIV viral load, together with significant covariates and potential confounders.
The time scale considered in this study was the number of months since ART initiation. Data were censored at the time of the first event among the following: death, WHO clinical stage 4 adverse event (for the analysis of disease progression), last visit for the patients lost to follow-up, or month 24 visit. The patients were considered lost to follow-up if their last visit occurred 3 months or more before the scheduled month 24 visit and if they were not known to be dead. All analyses were conducted using Stata version 12.1 (StataCorp, College Station, TX).
Characteristics of Patients and Follow-Up
Of the 459 patients, 324 (70.6%) were female, and median age at inclusion was 37 years [interquartile range (IQR) 30–45; Table 1]. Almost all the patients were at an advanced stage of HIV disease, 73.4% and 26.4% of them presenting with WHO clinical disease stage 3 and stage 4, respectively. Median CD4 cell count was 181 cells per microliter (IQR 87–337), and HIV viral load was 5.6 log10 copies per milliliter (IQR 5.2–6.1). Two hundred and thirty-eight patients (51.9%) were followed up using clinical monitoring alone and 221 (48.1%) with laboratory plus clinical monitoring. There was no significant difference between the 2 groups in terms of patient characteristics (Table 1) or outcomes.20
The total and median follow-up durations equaled 749.1 person-years and 24.0 months (IQR 21.7–24.0), respectively. Of 4141 clinical visits, 976 (23.6%) were conducted by nurses alone and 52 (1.3%) by both nurses and physicians. Nurses carried out 787 (37.4%) visits in the CLIN group and 189 (9.3%) in the LAB group. No association was found between the type of consultant seen at a given visit and the presence of a concomitant adverse event after adjustment for the visit and monitoring strategy (P = 0.222). The median overall consultant ratio was 0.11 (IQR 0.00–0.50; see Supplemental Digital Content 1,http://links.lww.com/QAI/A388). Thirty-eight (8.3%) patients were lost to follow-up at month 24. The consultant ratio did not differ statistically for those who were lost to follow-up and those who were not [odds ratio (OR) 0.88, 95% confidence interval (CI): 0.64 to 1.22, P = 0.442] after adjustment for gender, age, clinical stage, viral load, and CD4 cell count.
Viral loads below 40 copies per milliliter were observed in 60.0%, 63.4%, 69.3%, and 67.5% of patients after 6, 12, 18, and 24 months of ART, respectively. The consultant ratio was not significantly associated with virological success in univariate analysis (OR 0.96, 95% CI: 0.54 to 1.69, P = 0.876), in contrast to gender, baseline CD4 cell count, baseline viral load, and follow-up time point (ie, time of visit—at 6, 12, 18, or 24 months; Table 2). In the multivariate analysis, the consultant ratio remained unassociated with virological success (OR 1.00, 95% CI: 0.59 to 1.72, P = 0.990) after adjustment for gender, age, baseline CD4 cell count, baseline viral load, and follow-up time point.
CD4 Cell Count Evolution
The median increase in CD4 cell count was 160 cells per microliter (IQR 66–250) at month 6, 156 cells per microliter (IQR 81–253) at month 12, 208 cells per microliter (IQR 100–307) at month 18, and 231 cells per microliter (IQR 96–341) at month 24. In contrast to gender, age, baseline CD4 cell count, viral load, hemoglobin level, and follow-up time point, the consultant ratio was not significantly associated with CD4 recovery in the univariate analysis (coefficient 21.4, 95% CI: −11.1; 53.9, P = 0.197; Table 3). After adjustment for gender, age, baseline CD4 cell count, viral load, and follow-up time point, the consultant ratio was still not significantly associated with CD4 recovery (coefficient −3.6, 95% CI: −35.6; 28.5, P = 0.827).
Seventy-six (16.6%) patients died, giving a mortality rate of 10.1 deaths per 100 person-years (95% CI: 8.1 to 12.7). Survival was 88.0% at 6 months, 87.1% at 12 months, 84.5% at 18 months, and 82.8% at 24 months. In the univariate analysis, the consultant ratio was not significantly associated with time to death [time ratio (TR) 1.24, 95% CI: 0.23 to 6.73, P = 0.802], in contrast to gender, body mass index, clinical stage, CD4 cell count, viral load, and hemoglobin level (Table 4). When adjusted for gender, age, body mass index, CD4 cell count, and viral load, the consultant ratio was still not associated with death (TR 1.39, 95% CI: 0.27 to 7.06, P = 0.693).
Disease Progression to Death or to WHO Clinical Stage 4
Ninety-two (20.0%) subjects had progression to death (n = 58) or to a new/recurrent WHO stage 4 adverse event (n = 32) or both (n = 2); the incidence rate of disease progression was 12.7 per 100 person-years. Survival without WHO stage 4 adverse events was 85.4%, 83.8%, 81.0%, and 79.3% at months 6, 12, 18, and 24, respectively. The consultant ratio was not significantly associated with disease progression in univariate analysis (TR 1.25, 95% CI: 0.25 to 6.23, P = 0.784) unlike gender, body mass index, clinical stage, CD4 cell count, and viral load which were (Table 5). After multiple adjustment, the consultant ratio remained unassociated with disease progression (TR 1.60, 95% CI: 0.35 to 7.37, P = 0.543).
This study in rural district hospitals in Cameroon showed that task shifting from physicians to nurses does not compromise the patient outcomes in the first 2 years of ART. Our results were consistent with those of the CIPRA-SA and STRETCH trials and the reports of programmatic data.10–19 In another study using the Stratall data, we found that task shifting to nurses was associated with a better patient quality of life compared with the traditional physician-led monitoring of ART.22
Altogether these results are reassuring for the many African patients, healthcare workers, and program managers who face a severe shortage of physicians. Moreover, achieving universal access to HIV treatment in Africa by 2015, as encouraged by the United Nations Millennium Development Goals, will require a larger taskforce, as 51% of the 10.4 million African patients eligible for ART were not yet being treated as of December 2010, while new HIV infections exceeded treatment initiations.3 In August 2010, the Cameroonian national AIDS program officialized the monitoring of ART by nurses in conjunction with physicians.23
In our study, almost all the physicians and nurses were initially inexperienced in HIV care as the Stratall trial began simultaneously with the national program of decentralization of HIV care.24,25 Over the study period, numerous healthcare workers (mostly physicians) were transferred to other health facilities, generally being replaced by inexperienced staff. This reflects the routine clinical care situation in district hospitals and favors the generalizability of our findings to current routine care. However, our findings could have been different if the healthcare workers had been more experienced in HIV care, as the quality of care has been associated with professional experience.26,27
Training, mentoring, supervision, and referral are all crucial elements to achieving good quality ART care through task shifting.8 In our study, the nurses (like the physicians) were trained before and during the study period, worked together with the physicians within the clinics, were involved in the local therapeutic committee, which met weekly or fortnightly to discuss new or current patients, and were monitored every 2 weeks by clinical research assistants.
It is worth noting that the crisis in human resources is also affecting nurse staffing levels.5 However, training is shorter (3–4 years versus 7–9 years) and salaries are lower for nurses than for physicians. Nurses are also more plentiful and frequently present within the clinics than physicians do. The fact that nurses in our study were transferred less often to other health facilities than physicians—which is a great advantage to them both in terms of acquiring professional experience in the field of HIV and ART care and in building sustained relationships with patients—also supports the strategy of task shifting from physicians to nurses. Cost-effectiveness studies of task shifting to nurses are required in the local context and should take direct and indirect costs into account. In addition, national policies must be drawn up through consultation with professional healthcare associations to clearly delineate the tasks and responsibilities for nurses.28
One of the strengths of our study was the availability of regular clinical follow-up data. Another was that the effectiveness of the nurse-based care of treated patients was assessed with regard to physician-based care working in the same clinic. Furthermore, our study was performed in rural district hospitals where the number of physicians is small and where ART is now commonly provided in accordance with the WHO-recommended strategy of decentralized, integrated delivery of care.7 Finally, the representativeness of the nurses and physicians in our study was good as they were involved in routine hospital activities, were not specialists in HIV care (who work in reference clinics), and were not supported by additional study staff.
Our study has several limitations. First, the patients were followed up for 24 months. Yet the quality of care provided by nurses could be less favorable in the longer term than that provided by physicians, as the management of patients becomes more complex due to therapeutic failures, HIV resistances, and drug-related side effects. Second, our data were recorded in the context of a trial. The representativeness of our study population and procedures could therefore be questionable. Nevertheless, our patients were comparable with those followed up in the Cameroonian national AIDS program and our study procedures incorporated the good clinical practices required in such settings.24 Third, the patients were not randomly assigned to nurses or physicians. Although the type of consultant seen at a given visit was not associated with the presence of a concomitant adverse event, a selection bias cannot be ruled out as the sickest patients may have been preferentially consulted by physicians. However, the organization within our clinics does not suggest this. Fourth, because our study assessed the effectiveness of task shifting in patients followed up by on-site nurses and/or physicians—as this is likely the actual situation in current routine clinical care when both professional groups are present—our findings may not be generalizable to health facilities without on-site physicians.
In conclusion, this study brings important evidence about the comparability of ART-related outcomes between HIV models of care based on physicians or nurses in resource-limited settings. The lack of physicians should therefore not be used as a pretext to inhibit ART expansion. However, physicians remain key actors in ART care, especially for the management of complex cases (which are likely to become more frequent as patients accumulate years on ART), and mentoring and supervision activities. Investing in nursing resources for the management of noncomplex patients should help to reduce costs and patient waiting lists while freeing up physician time to carry out these essential activities and other health interventions.
The authors thank all the patients and staff of the district hospitals who participated in the study and Jude Sweeney (Rome, Italy) for the English revision and editing of the article.
STRATALL ANRS/ESTHER STUDY GROUP
M. Biwolé-Sida, C. Kouanfack, S. Koulla-Shiro (Central hospital, Yaoundé, Cameroon); A. Bourgeois, E. Delaporte, C. Laurent, M. Peeters (IRD, University Montpellier 1, UMI 233, Montpellier, France); G. Laborde-Balen (French Ministry of Foreign Affairs, Yaoundé, Cameroon); M. Dontsop, S. Kazé, J.-M. Mben (IRD, Yaoundé, Cameroon); A. Aghokeng, M. G. Edoul, E. Mpoudi-Ngolé, M. Tongo (Virology Laboratory, IMPM/CREMER/IRD-UMI 233, Yaoundé, Cameroon); S. Boyer, M. P. Carrieri, F. Marcellin, J.-P. Moatti, B. Spire (INSERM, IRD, University Marseille, UMR 912, Marseille, France); C. Abé, S.-C. Abega, C.-R. Bonono, H. Mimcheu, S. Ngo Yebga, C. Paul Bile (IRSA, Catholic University of Central Africa, Yaoundé, Cameroon); S. Abada, T. Abanda, J. Baga, P. Bilobi Fouda, P. Etong Mve, G. Fetse Tama, H. Kemo, A. Ongodo, V. Tadewa, H. D. Voundi (District Hospital, Ayos, Cameroon); A. Ambani, M. Atangana, J.-C. Biaback, M. Kennedy, H. Kibedou, F. Kounga, M. Maguip Abanda, E. Mamang, A. Mikone, S. Tang, E. Tchuangue, S. Tchuenko, D. Yakan (District Hospital, Bafia, Cameroon); J. Assandje, S. Ebana, D. Ebo'o, D. Etoundi, G. Ngama, P. Mbarga Ango, J. Mbezele, G. Mbong, C. Moung, N. Ekotto, G. Nguemba Balla, G. Ottou, M. Tigougmo (District Hospital, Mbalmayo, Cameroon); R. Beyala, B. Ebene, C. Effemba, F. Eyebe, M.-M. Hadjaratou, T. Mbarga, M. Metou, M. Ndam, B. Ngoa, E. B. Ngock, N. Obam (District hospital, Mfou, Cameroon); A. M. Abomo, G. Angoula, E. Ekassi, Essama, J. J. Lentchou, I. Mvilongo, J. Ngapou, F. Ntokombo, V. Ondoua, R. Palawo, S. Sebe, E. Sinou, D. Wankam, I. Zobo (District hospital, Monatélé, Cameroon); B. Akono, A. L. Ambani, L. Bilock, R. Bilo'o, J. Boombhi, F. X. Fouda, M. Guitonga, R. Mad’aa, D. R. Metou’ou, S. Mgbih, A. Noah, M. Tadena, Ntcham (District hospital, Nanga Eboko, Cameroon); G. Ambassa Elime, A. A. Bonongnaba, E. Foaleng, R. M. Heles, R. Messina, O. Nana Ndankou, S. A. Ngono, D. Ngono Menounga, S. S. Sil, L. Tchouamou, B. Zambou (District hospital, Ndikinimeki, Cameroon); R. Abomo, J. Ambomo, C. Beyomo, P. Eloundou, C. Ewole, J. Fokom, M. Mvoto, M. Ngadena, R. Nyolo, C. Onana, A. Oyie (District hospital, Obala, Cameroon); P. Antyimi, S. Bella Mbatonga, M. Bikomo, Y. Molo Bodo, S. Ndi Ntang, P. Ndoudoumou, L. Ndzomo, S. O. Ngolo, M. Nkengue, Nkoa, Y. Tchinda (District hospital, Sa'a, Cameroon).
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