Improvement in anaemia in majority of US patients after starting AZT reported in large review

HIV therapy that includes AZT (zidovudine, Retrovir) is a safe and effective option for HIV-positive people with anaemia, say investigators in the June 1^st issue of the Journal of Acquired Immune Deficiency Syndromes. However, they suggest decisions should be made case by case, as black patients and people with mild cases of anaemia may be slower to respond.

AZT, one of the first anti-HIV drugs, has been superceded in the developed world by other equally effective and more tolerable options. However, due to its wide availability and its affordability, the drug is still a common treatment option in many developing nations, often in fixed-dose combinations.

Anaemia, which is common among people with advanced HIV disease, is also a potential side-effect of AZT. This is of particular concern in settings where the blood deficiency is widespread due to factors such as malaria, malnutrition or other non-HIV related causes.

While HIV-associated anaemia usually improves after the initiation of antiretroviral therapy —with or without AZT—a more nuanced understanding is lacking. To address this gap, investigators at the US Centers for Disease Control (CDC) performed a retrospective study of records in the Adult and Adolescent Spectrum of HIV Disease (ASD) project, a study following HIV-positive people at over 100 medical facilities in 11 cities across the US.

From the project database, investigators selected 1620 records of patients who were treatment-naïve with no previous AIDS-defining infections but with laboratory measures indicating anti-HIV treatment was warranted. Researchers then compared haemoglobin (Hb) levels, a marker of anaemia, before starting antiretroviral therapy and every six months after starting HIV therapy. Patients were followed for a median of 21 months and had a median of three haemoglobin measurements. Patients were excluded if they had a history of treatment for anaemia.

Hb levels used to categorise anaemia differed by gender. Men were considered nonanaemic if their Hb levels were above 14 g/dL, while women were non-anaemic if their Hb levels were above 12 g/dL. For both men and women, Hb ≤ 8.0 g/dL was considered severe anaemia and 8 > Hb ≤ 10 g/dL, moderate anaemia. Mild anaemia was 10 > Hb ≤ 14 g/dL for men, and 10 > Hb ≤ 12 g/dL for men.

Before starting antiretroviral therapy, 543 (34%) had no anaemia, 848 (52%) had mild anaemia, 174 (11%) had moderate anaemia and 55 (3%) had severe anaemia.

Over the entire follow-up period, 54% of patients starting antiretroviral therapy showed an improvement in anaemia. When categorised by severity, 47% of cases of mild anaemia saw improvement, compared with 79% of moderate cases and 87% of severe cases. Investigators scored improvement as an increase in Hb levels of at least 1.0 g/dL from baseline along with an improvement in severity category.

Patients with mild anaemia who received AZT were less likely to show improvement than those not receiving AZT at 12 months (p = 0.0006). This was also true when calculating the cumulative probability of improvement over the entire follow-up period. For patients with moderate and severe anaemia, there was no difference between AZT and AZT-sparing regimens.

Investigators then analysed the data to identify factors associated with time to improvement. Improvement was faster in moderate (hazard ratio (HR) 3.2, 95% CI 2.6 to 3.9) or severe cases (HR 5.3, 95% CI 3.9 to 7.3). It was also faster in cases with immunosupression (CD4 cell count 3; HR 1.3, 95% CI 1.0 to 1.5, p = 0.02). Improvement was slower in cases with AZT and in black patients. Both factors were associated with a hazard ratio of 0.7 (95% CI 0.6 to 0.9).

Finally, investigators analysed data from among patients who did not have anaemia before starting therapy: 253 of 543 developed anaemia during follow up. However, including AZT did not increase the chance of developing anaemia over time. The 12-month probability was 58% for those receiving AZT and 62% for those not receiving the drug in the intent-to-treat analysis.

Antiretroviral therapy improves anaemia, the investigators state, but the “inclusion of AZT in the initial [antiretroviral] regimen may prolong the time to improvement of anemia by up to 30%.” Improvement was also lower among black patients. This has been noted in other studies, and the investigators suggest that factors unrelated to HIV, such as sickle cell disease or iron deficiency, may be affecting how black patients respond to therapy.

“Based on our findings,” they write, “we conclude that on a population basis, the use of AZT in an initial antiretroviral regimen is a medically rational choice, even for patients with preexisting anemia. For most patients with HIV infection and anemia, initiating [antiretroviral therapy] with or without AZT results in improvement of anemia. Alternative regimens should be considered for patients in whom rapid resolution of anemia is clinically important or for whom clinically relevant anemia develops after initiation of an AZT-containing regimen.”

While these findings are important to consider in places such as Africa, the investigators acknowledge that environmental and genetic differences between populations in the US and Africa make it difficult to apply the findings in a meaningful way. Local evidence is the best way to develop local treatment options, they finish.