Practical Management of HIV-Associated Anemia in Resource-Limited Settings: Prospective Observational Evaluation of a New Mozambican Guideline

Abstract

Mozambique's updated guideline for management of HIV-associated anemia prompts clinicians to consider opportunistic conditions, adverse drug reactions, and untreated immunosuppression in addition to iron deficiency, intestinal helminthes, and malaria. We prospectively evaluated this guideline in rural Zambézia Province. Likely cause(s) of anemia were determined through prespecified history, physical examination, and laboratory testing. Diagnoses were ''etiologic'' if laboratory confirmed (sputum microscopy, blood culture, Plasmodium falciparum malaria rapid test) or ''syndromic'' if not. To assess hemoglobin response, we used serial point-of-care measurements. We studied 324 ambulatory, anemic (hemoglobin <10 g/dl) HIV-infected adults. Study clinicians treated nearly all [315 (97.2%)] for suspected iron deficiency and/or helminthes; 56 (17.3%) had laboratory-confirmed malaria. Other assigned diagnoses included tuberculosis [30 (9.3%)], adverse drug reactions [26 (8.0%)], and bacteremia [13 (4.1%)]. Etiologic diagnosis was achieved in 79 (24.4%). Of 169 (52.2%) subjects who improved (hemoglobin increase of ‡1 g/dl without indications for hospitalization), only 65 (38.5%) received conventional management (iron supplementation, deworming, and/or antimalarials) alone. Thirty (9.3%) died and/or were hospitalized, and 125 (38.6%) were lost to follow-up. Multivariable linear and logistic regression models described better hemoglobin responses and/or outcomes in subjects with higher CD4 + T-lymphocyte counts, pre-enrollment antiretroviral therapy and/or co-trimoxazole prophylaxis, discontinuation of zidovudine for suspected adverse reaction, and smear-positive tuberculosis. Adverse outcomes were associated with fever, low body mass index, bacteremia, esophageal candidiasis, and low or missing CD4 + T cell counts. In this severely resource-limited setting, successful anemia management often required interventions other than conventional presumptive treatment, thus supporting Mozambique's guideline revision.

Severe anaemia complicating HIV in Malawi; multiple co-existing aetiologies are associated with high mortality

“…However, the contribution of malaria to anaemia in our study population was small however, as only 6 patients (3.5%) had malaria parasites on presentation. This is in line with data from other studies that show that the role of malaria in causing anaemia, especially in HIV patients in sub-Saharan Africa (2, 14), is limited and likely to have been overestimated (40, 45).…”

“…In our study patients TB was a common co-infection (41%). This prevalence is comparable to previous reports on TB prevalence (43%) among severely anaemic HIV-infected patients in Africa (8, 14). The pathophysiology of TB-associated anaemia in HIV-infected patients remains unclear.…”

“…Malaria is unsurprisingly associated with severe anaemia in HIV-infected patients in sub-Saharan Africa (2, 14). However, the contribution of malaria to anaemia in our study population was small however, as only 6 patients (3.5%) had malaria parasites on presentation.…”

“…As a consequence, evidence to inform preventive or treatment guidelines for severe anaemia in HIV-infected patients in sub-Saharan Africa is scarce. In practice, severe anaemia management in HIV-infected patients is often still based on the same strategies used for non-HIV infected patients, including iron supplementation, malaria treatment and de-worming (2, 14). This strategy may be ineffective as the causes of HIV-associated severe anaemia may be different, and even harmful considering that (blind) iron supplementation may exacerbate infections and thus may deteriorate the patients condition (15, 16).…”

<p>HIV Treatment Outcomes Among Patients Initiated on Antiretroviral Therapy Pre and Post-Universal Test and Treat Guidelines in South Africa</p>

“…2,[33][34][35] HIV-positive patients with anaemia are often subject to other opportunistic infections, complications in treatment and disease progression; common risk factors to both mortality, disengagement with health services and potentially progression to higherlevel facilities/hospitalization. 36,37 Patients initiating ART under UTT and those with higher CD4 cell counts (>200 cells/mm 3 ) were at least 15% more likely to achieve virologic suppression at 12 months on ART. While this may be a marginal increase, the higher suppression rates among those in better health at the start of treatment may speak to the rationale behind earlier ART initiation (at a higher CD4 cell count).…”