We assessed Hb levels, white blood cell counts and platelet counts in HIV-infected antiretroviral naïve and uninfected Rwandan women, and found that greater anaemia, neutropenia and thrombocytopenia were all associated with HIV-positive serostatus. While anaemia and neutropenia in HIV-infected women were strongly associated with lower CD4 cell counts, thrombocytopenia was not. To that end we have compared the prevalence of abnormal haematological parameters we observed in HIV-positive women with those seen in five studies in sub-Saharan Africa and Western World ().
Prevalence of anaemia, neutropenia and thrombocytopenia in HIV-infected women in five studies
Most notably, although our findings indicated that the HIV-infected women had lower mean Hb and were more likely to have anaemia or marked anaemia than HIV-negative women, the proportions of HIV-infected (as well as uninfected) women with anaemia here were lower than those from prior published studies of women in sub-Saharan Africa and Western Countries.18
For example, the mean Hb observed here of 13.1 g/dl for HIV+ and 14.5 g/dl for HIV-uninfected women were each about a full point higher in both the HIV-infected and the HIV-uninfected women compared with 2056 HIV-infected (Hb 12.3 g/dl) and 569 HIV-uninfected (Hb 13.0 g/dl) participants in the Women's Interagency HIV Study (WIHS).18
Lower Hb levels in HIV-infected than uninfected individuals are nearly universally observed, and our finding is similar to prior studies from sub-Saharan Africa, for example, HIV-infected women were more likely to be anaemic than HIV negative women (23.6% vs 12.8%; p=0.031) in a Ugandan study.20
In a recent Rwandan study of 200 HIV-infected (of whom 50 were on ART) and 50 uninfected women, the prevalence of anaemia was similar to our study (29% and 8%, respectively).23
Poor nutritional status may also cause anaemia,17
which may be reflected in the association of anaemia with lower BMI in this urban Rwandan population.
The higher Hb levels in the Rwandan women, with and without HIV infection, than elsewhere may be attributable to the higher altitude of Rwanda, a mountainous country, with an elevation above sea level of 1500 m in Kigali, the capital city and site of this study.24
The high Hb observed in this cohort of Rwandan women may be due to acclimatisation to higher altitude ensuring that women living in high-altitude regions of Rwanda have similar physiological adaptations as those living at lower-altitude levels.25
High-altitude adaptations to fall in partial pressure of oxygen reduces the driving pressure needed for diffusion of oxygen across the alveolar-capillary barrier, and thus a fall in arterial partial pressure of oxygen. This results in reduction of oxygen delivery to body tissues and thus potential cellular hypoxia and organ dysfunction.26
Thus, living in higher altitude may have resulted in a fall of arterial oxygen content and reduced oxygen tissue delivery. This may have resulted in participants’ adaptation to ensure restoration of arterial oxygen saturation, which increases Hb concentration in individuals who habitually reside in high-altitudes areas, a principle used by endurance athletes.27
We have reported higher prevalence of neutropenia in the HIV-infected than uninfected Rwandan women, a common finding in sub-Saharan Africa.20
Neutropenia may be due to HIV suppression of bone marrow resulting in abnormal granulopoesis. Antigranulocyte antibodies have been described in HIV-infected persons,29
and neutropenia observed in HIV-infected adults may be attributed to decreased production of granulocyte colony-stimulating factor.30
It should be noted that one study from Nigeria among HIV-infected persons found a mean WBC count that was higher than the mean values for HIV-infected women in our study.21
This difference could be attributed to different stages of HIV illness in the study populations and the fact that participants in our study were ART-naïve, which was not true for the Nigerian study.
In our study, neutropenia observed in HIV-infected women was of higher prevalence in women with CD4 lymphocyte count <200 cells/μl. Similarly, the WIHS found baseline neutropenia, defined as <2000 cells/mm3
, in 44% of women participants and a longitudinal analysis found that worsening HIV disease was associated with subsequent neutropenia.10
Neutropenia in an Ivory Coast study was observed in 21% of HIV-infected patients starting co-trimoxazole prophylaxis, but low-grade neutropenia was not associated with adverse clinical consequences31
as is also the case in other sub-Saharan African countries. Neutropenia in our study was independently associated with low CD4 lymphocyte count, and this suggests that the stage of HIV-infection is an important determinant to pretreatment neutropenia.
We observed a higher prevalence of thrombocytopenia (platelets ≤125.0×103
/μl) in HIV-infected compared to HIV-uninfected women, but no association between thrombocytopenia and CD4 count within HIV-infected women. In developed countries, thrombocytopenia is generally infrequent in healthy asymptomatic HIV-infected patients, and is associated with very advanced HIV disease and comorbidities.32
However, thrombocytopenia has been shown to be one of the common haematological abnormalities in patients before HAART initiation in sub-Saharan countries.28
Although HIV-infected women in our study were HAART-naïve, the majority was asymptomatic and few reported WHO stage IV illness, and as noted may not have had advanced HIV disease.
Our study has some limitations. Its non-randomised cross-sectional design makes it structurally impossible to determine temporal direction or causality including inability of multivariate models to adjust for all confounding. Second, all participants in this study were women, and as Hb levels differ between men and women, our findings cannot be extrapolated to men. Finally, the small number of women with WBC <2.0 cells/mm3 resulted in inadequate power to assess predictors of neutropenia. It is possible, or even likely, that the large OR for the associations of co-trimoxazole use (OR=5.69 CI 0.63 to 51.45) and CD4 count <200 cells/mm3 (OR=7.18 CI 0.78 to 65.82) with neutropenia would be significant with a larger sample size.
In conclusion, we observed high prevalence of anaemia in HIV-infected and uninfected Rwandan women. Anaemia was more common in the HIV-infected than in uninfected women, especially those with greater disease progression as indicated by lower CD4 cell counts. Neutropenia and thrombocytopenia were more common in the HIV-infected than in uninfected Rwandan women. As anaemia and neutropenia are the most common haematological abnormalities in HAART-naïve HIV-infected women, it is important to routinely assess these parameters for timely and adequate clinical management.