Spirometric profile of people living with HIV on antiretroviral drugs in Abidjan

The study population was composed of 409 women (59.3%) and 356 men (40.7%), with an average age of 48.9 ± 10.8 years with ages ranging from 24 to 79 years. The age group 40 to 50 years represented 42.6%. (Table 1).

PLHIV mostly worked in the informal sector (46.3%), the majority had attended the secondary level of education (37%) followed by the primary level (29.6%).

The majority (63%) of patients had been known to be PLHIV for at least 10 years with an average seniority of 11.3 ± 5.6 years and a standard deviation of 5.6 years (extremes: 1 – 21 years). All patients were on ART at the time of the study (100%). Among them 59.3% had been on ART for at least 10 years. The average duration of ART was 10.4 ± 5.3 years (extremes: 1 – 21 years). The majority of patients (77.8%) were on the Tenofovir/Lamivudine/Dolutegravir (TLD) triple therapy with good adherence to the ART in 94.4% of cases. (Table 1)

The CD4 count at diagnosis of HIV infection had a median of 240.5 (82.3 – 419) cells/mm³ (range: 1 – 709 cells/mm³). Majority of the patients had moderate immunosuppression (48.1%). The median viral load was 20 (1-50) copies/ml (range: 0 – 306.000 copies/ml) and was detectable in 51.9% of patients. Patients who received cotrimoxazole chemoprophylaxis represented 25.9% compared to 3.7% who received isoniazid.

A history of lung infection was the most common (48.1%). Of these, pulmonary tuberculosis was the most frequent (35.2%). The larger number of our patients were non-smokers (81.4%). Biomass smoke (25.9%) and pesticides (7.4%) were the airborne contaminants to which PLHIV were most exposed. The average duration of exposure to biomass smoke was 24.3 ± 11.1 years and that of exposure to pesticides was 13.9 ± 5.9 years. Chronic respiratory symptoms found in 16 patients (29.6%) were mainly dyspnoea (16.7%) and dry cough (13%). The Body Mass Index (BMI) was normal in 42.6% of patients with an average BMI of 25.5 kg/m² ± 4.5 kg/m² (extremes: 17.1 – 35 kg/m²).

The majority of patients (72.2%) had a normal FEV1 with an average FEV1 of 90.1 ± 16.0% of theoretical (extremes: 64 – 128%). The average FVC was 97.7 ± 15.8% of the theoretical (extremes: 63 – 133%) and 87% of the patients had a normal FVC. The mean Tiffeneau ratio was 77.8 ± 6.5% (range: 56.7 – 91.2%). This ratio was normal in 94.4% of patients. The average FEF25 – 75 was 63.1 ± 22.6% (extremes: 26 – 135%). More than half of the patients (59.3%) had a FEF25 – 75 higher than the norm. The frequency of spirometric abnormalities was 57.4%. Peripheral obstructive ventilatory defect (40.7%) was the most frequent ventilatory anomaly (Figure 2).

Figure 2.Spirometric abnormalities identified in patients

The factors associated with spirometric abnormalities were a more than 10 years duration since the diagnosis of HIV infection (p=0.001 OR= 0.2 (0.1 – 0.7) and an ART of at least 10 years (p=0.001 OR= 0.2 (0.1 – 0.7). However, there was no significant link between socio- demographic characteristics (gender, age, level of education), history of lung infection and smoking, respiratory symptoms, BMI and the presence of spirometric abnormalities (Table 2).

One of the weaknesses of our study lies in the non-inclusion of 29.65% of cases due to the inability to perform spirometric manoeuvres, responsible for our small sample size. The retrospective component of our study limited the data collected to the sole information available in the patients’ files such as biological data (viral load, CD4 count), some of which were absent. However, the CD4 count and viral load are no longer mandatory for ART initiation. Finally, our analysis of ventilatory function was limited to spirometry. The presence of a RVD in spirometry requires plethysmography for confirmation of this disorder. Despite these limitations, to the best of our knowledge, this study is one of the first in Côte d'Ivoire to assess the ventilatory function of PLHIV. It analysis the profile of spirometric abnormalities observed in PLHIV treated with ARVs.

The mean age of the patients was 48.9 years with a standard deviation of 10.8 years. The age group of 40 to 50 years was the most represented (42.6%). Our results are close to the average age reported in many studies, particularly in the USA ¹⁸, South Africa ¹⁹ and Cameroon ¹³ which found an average age of 50, 43.5 and 42.6 years old respectively.

Our study population was mainly composed of women (59.3%) with a sex ratio M/F of 0.68. In the world population and particularly in Côte d'Ivoire, the prevalence of HIV is higher in women than in men ^{1, 12}.

The frequency of ventilatory anomalies in our study was 57.4%. This is higher than what is found in the literature mainly because of the peripheral OVDs which were not sought in these various studies ^{13, 19, 5, 18, 20}. The prevalence of peripheral OVD was 40.7% in our work. We did not find in the literature a study focusing on this peripheral damage, which would reflect damage to the small bronchi without abnormality of the large bronchi. Particularly in the early forms of COPD, inflammation and structural changes begin and predominate in the distal airways ²¹. Unlike peripheral OVD, that of asthma was 3.7% in our study population. This frequency is lower than the hospital frequency of 5.2% for asthma found by Pefura-Yone et al. in Cameroon in 2015 ¹³ and at 7% by Van Riel et al in South Africa ¹⁹. The frequency of asthma in our study is higher than the 2.99% found by Koffi N et al in Abidjan, Côte d'Ivoire in 2001²² and the 2.7% found by Hirani et al in their study ²⁰. The prevalence of COPD in our study population was 3.7%. This proportion was higher than the Ivorian hospital prevalence of COPD found by Anon et al in 2020, which was 2.5% ²³. On the other hand, our frequency of COPD was significantly lower than those reported by several African and Western studies where it varied from 5.2 to 27%. ^{5, 13, 18, 19, 20} This difference could be explained by the higher percentage of smoking patients/former smokers in these different studies than that of our series where the majority of our patients (81.4%) were non- smokers. This high proportion of non-smoking patients is consistent with most studies conducted in sub-Saharan Africa ^{13, 6, 19}, but remains lower than that of Western studies ^{2, 5, 18, 20, 11}. It is already established that smoking is a risk factor or even aetiology of COPD and several studies have demonstrated in their cohort of PLHIV, smoking as a risk factor for the development of non-reversible OVD ^{13, 5, 18}. However, in sub-Saharan Africa, another risk factor to consider in the occurrence of COPD is environmental exposure, particularly to biomass (25.9% in our study). The frequency of RVD in our series (9.3%) is close to that reported by Drummond et al (10%), although slightly higher than that of the general American population of 7% ¹⁸. The prevalence of RVD was 38% in Cameroon among PLHIV naïve to ART ²⁴. Given the history of pleuropulmonary infection (48.1%), one would have expected a higher frequency of RVD among the PLHIV in our series. This low frequency of RVD could be related to the almost complete recovery of the lung parenchyma and pleura following these infections, with very few sequelae.

Previous studies have clearly demonstrated age as a factor associated with spirometric abnormalities in PLHIV ¹⁹, particularly in the 40 to 50 years age group ¹⁸. This age group was independently associated with the presence of RVD ¹². In our series, this link was not significant. Similarly, male sex has been identified as a risk factor for developing spirometric disorders in PLHIV ^{19, 25}, but this association was not significant in our study. Other elements, particularly the low level of education (below secondary) have been described as a factor associated with RVD ²⁶. However, this was not the case in our study. The duration since HIV diagnosis was on average 11.3 years. A less than 13 years average duration of HIV diagnosis was obtained by Gingo et al in the United States ⁵, but was significantly higher than the 6.25 years obtained by van Riel et al in South Africa ¹⁹. Patients with a more than 10 years diagnosis of HIV had significantly more ventilatory abnormalities (p=0.001). Similar observations have been made both in Europe and in Africa. Indeed, Kristoffersen et al in Denmark found an average duration of infection of 9.25 years and a duration of infection greater than 10 years significantly associated with the presence of OVD ²⁷. Drummond et al ¹¹ also found the prolonged duration of HIV infection as a risk factor for developing a ventilatory defect. This increased risk of ventilatory abnormalities with duration of HIV exposure could be explained by direct virus-related pulmonary toxicity, persistent systemic inflammation, altered antioxidant/oxidant balance resulting in oxidative stress, and accelerated immune deterioration. However, ART and duration would also play a role in the occurrence of ventilatory abnormalities. The average duration of ART instituted according to the WHO regimen was 10.4 years. Patients on ART for at least 10 years in our series had significantly more ventilatory abnormalities (p=0.001). TDF+3TC+DTG triple therapy was the most widely used treatment (77.8%) and the majority of our patients (94.4%) were adherent to treatment. Several studies also found an association between the duration of ART and the existence of a ventilatory abnormality. Indeed, Gingo et al in the United States found ART as a risk factor for developing non-reversible OVD. However, the triple therapy used was not specified in this study ⁵. George et al reported that ART use was independently associated with the development of OVD ¹⁰. The link between ART and ventilatory disorders is not known, but potential explanations include the direct effects of ART in the lungs, the restoration of the immune system resulting in a renewed response to subclinical infections and/or the development of auto–immunity. ART-associated cardiovascular diseases, metabolic syndrome, and osteoporosis may be directly linked to antiretroviral agents, particularly protease inhibitors ²⁸, but there are no published reports of antiretroviral drugs and ventilatory disorders. On the other hand, literature notes a link between the degree of immunosuppression and the occurrence of ventilatory anomalies in this population. Several series ^{5, 7, 10, 11, 29} have found an association between low CD4 count, the high viral load and the development of ventilatory disorders. However, these data may not be applicable to patients with less severe immunodeficiency, as is the case in our study where 48.1% had moderate immunosuppression and an undetectable viral load. Whatever the case, ventilatory anomalies will lead to respiratory manifestations which may vary according to the patient's smoking profile. In our series, the high proportion of non-smokers (81.4%) observed is consistent with most studies conducted in sub-Saharan Africa ^{13, 6, 19, 26} but remains lower than those of Western studies ^{2, 5, 18, 20, 11, 29}. Indeed, the prevalence of smoking in sub- Saharan Africa in the general population remains lower than that observed in the Western world. It has already been established that smoking is a risk factor or even an aetiology of COPD, but also described as a factor in the development of non-reversible OVD in PLHIV ^{5, 13, 18}. However, in sub-Saharan Africa, another risk factor to consider in the occurrence of COPD is environmental exposure, particularly to biomass (25.9% in our study). A history of pleuropulmonary infection was found in 48.1% of our patients and consisted mainly of pulmonary tuberculosis (35.2%). It has been demonstrated that PLHIV with a history of pulmonary tuberculosis are more at risk of developing RVD ^{5, 12, 26} and sometimes OVD ^{13, 19, 29}, but the association was not statistically significant, possibly because of our small sample. Indeed, tuberculosis through its sequelae can lead to ventilatory restriction in these patients who are sometimes undernourished or even emaciated. Underweight (defined by a BMI<18.5 kg/m²) was found by certain series to be a risk factor for developing a ventilatory anomaly ⁶. In our study, we did not find an association between BMI and the presence of ventilatory abnormality. This could be explained by the fact that the majority of our patients had a normal BMI (42.6%). Similarly, only 29.6% complained of chronic respiratory symptoms despite the high prevalence of ventilatory abnormalities. Gingo et al as well as Drummond et al had also found a discrepancy between patient complaints and the presence of ventilatory abnormalities ^{18, 30}. This would mean that one should not always wait for the complaint of dyspnoea or chronic cough to consider spirometry for a PLHIV. Spirometry should therefore be part of the respiratory assessment of PLHIV whether they have chronic respiratory symptoms or not. However, the profile of these patients should be well defined.