Immunologic and virological response to ART among HIV infected individuals at a tertiary hospital in Ghana

Human Immunodeficiency Virus (HIV) infection is still a major public health problem worldwide. Sub-Sahara Africa is home to at least 23 million infected people, most of whom report late to clinics for treatment [1, 2]. HIV infects and gradually depletes immune cells mainly CD4 lymphocytes which are key in cell-mediated response as well as contributing to humoral response against invaded pathogens [3]. As a result of immune destruction, severe morbidity and mortality which may also be associated with opportunistic infections are observed among those infected [4].

Globally, 20.9 million infected people were estimated to be receiving Anti-retroviral Therapy (ART) by June 2017 [5]. The antiretroviral (ARV) drugs, mostly used in combination of three, are targeted at inhibiting viral replication and subsequently maximizing reduction in viral load (VL) leading to recovery of immune function [3, 6]. Thus, ART reduces HIV associated morbidity and mortality and enables infected persons to enjoy quality and productive life.

Viral Load and CD4 counts are important markers for assessing treatment response and immune recovery in patients on ART. WHO recommends that VL and or CD4 testing where available should be done prior to ART, at 6 and 12 months after initiation of ART and then at least every 12 month once the patient becomes stable on ART [6]. This is to enable medical personnel to confirm suspected treatment failure detected clinically and to provide the necessary intervention such as adherence support and ART regimen switching [6]. Currently, treatment failure in Ghana is defined virologically (gold standard) as viral loads persistently more than 1000 copies of HIV RNAs/ml of blood plasma and or immunologically when CD4 counts are persistently at or below 250 cells/mm³ after 12 months on ART [7].

Recently, attention has been focused on immune recovery among Persons Living with HIV (PLHIV) on ART. Studies have highlighted the significance of ART and factors that may influence the outcomes of ART and immune recovery and these help to provide effective or better patient management and intervention. It has been reported that individuals who start ART at higher CD4 count baseline (≥300 cells/mm³) have their CD4 cell counts returning to nearly normal or normal (≥500 cells/mm³) than those who starts at lower baselines (≤200 cells/mm³) [8, 9]. Some studies have shown a link between viral suppression and improved immune response while on ART [10‐12].

Little is known about the outcome of ART among HIV infected individuals in Ghana, a sub-Saharan African country with an estimated HIV prevalence of 1.47% [13]. There have been some studies focusing on the outcome for patients on specific ARVs and also the paediatric population [14, 15]. The aim of this study was to analyze the determinants of immunological and virological response to ART among HIV infected individuals in a tertiary facility in Cape Coast, Ghana.

The main goal of ART for people living with HIV (PLHIV) is to achieve virological suppression and immune system recovery. This would ensure quality healthy living and continuous contribution to families, community and country as a whole. Such viral suppression would also very importantly reduce the risk of HIV transmission to sexual partners and from mother to child [16‐18]. Many factors affect the response to ART and this study aimed at determining these factors among this study population after a minimum of 6 months on ART.

This study found that after 6 months and 12 months on ART, the number of participants who had achieved viral copies < 1000/ml rose from 149 (47.0%) to 368 (89.6%) respectively. In fact, 2 people (0.6%) had achieved complete viral suppression (undetectable viral copies) after 6 months on ART, but this number rose to 85 (20.7%) after 12 months. This virological suppression on first line ARVs is very encouraging and comes close to the new global UNAIDS target which indicates that by the year 2020, at least 90% of all clients initiated on ART should have achieved virological suppression after 12 months on ART [19]. WHO recommends that early initiation of ART in positive persons would improve response and help countries to most likely achieve the 2020 target for virological suppression [20]. It is noteworthy that, in this study as much as 318 (72.3%) of clients were initiated into ART when they already had WHO clinical stage 3 or 4 conditions. In a study in Ghana, Kwakye-Nuako et al. (2016) found that clients with CD4 count < 200 cells/mm³ had increased prevalence of diarrhoea causing opportunistic pathogens (WHO clinical Stage 4 pathogens) [21] and such conditions would influence the response to therapy. Ghana has currently adopted the “Treat All” policy which ensures that all confirmed HIV infected individuals in Ghana qualify for ART and efforts are to be made to initiate as soon as possible [7]. Immunologically, the mean CD4 count at baseline, 6 months on ART and at recruitment into this study were 215.1 cells/mm³, 386.6 cells/mm³, and 579.6 cells/mm³ respectively showing a progressive rise as expected. There was strong evidence of an association between having CD4 count < 350 cells/mm³ after 6 months on ART and having plasma viral load > 1000 copies/ml (aOR 2.0, 95% CI 1.2–3.2, p = 0.01). These findings agree with the knowledge that, viral suppression leads to immune recovery. Some studies looking at the relationship between CD4 count and virological suppression have found discordant relationship in some participants where virological suppression does not reflect in the rise in CD4 count. Casotti et al. (2011) attributed this to delays in initiating ART [22] while Kelly et al. (2016) in their systematic review on clinical outcomes, found increased mortality among clients with such discordant response [23].

In this study, the mean age of participants was 45.5 years (±11.6), this implies a relatively older population initiated on ART. In this study, age was not found to predict a client having CD4 count < 350 cells/mm³ after 6 months on ART on both bivariate and multivariate analysis. A study by Gezie et al. (2016) in Ethiopia found that younger age contributed to higher increment of CD4 count on ART [24]. Other studies have also been reported by studies in other settings [25] while others have found that in the long term older clients achieved similar virological suppression compared with younger clients [26]. Majority (346, 78.6%) of participants were female which is consistent of the gender distribution of the HIV population in Ghana and even globally. And in this study there was no evidence of an association between gender and having CD4 count < 350 cells/mm³ after 6 months on ART as also reported by other studies [27, 28]. In a large study conducted in Canada, Cescon et al. (2014) reported that women were at heightened risk of having poor response to ART but did conclude that this needs further research [29]. The fact is that these socio-demographic factors all influence adherence to ART and any factor which leads to poor or sub-optimum adherence would affect the response to therapy and these include employment status, the issue of disclosure to sexual partners etc. [30‐32]. The association between tuberculosis and HIV is also well established and in this study there was strong evidence of an association between having CD4 count < 350 cells/mm³ after 6 months on ART and having a diagnosis of tuberculosis (aOR 8.5, 95% CI 1.1–73.0, p = 0.05). This association informed the policy which is also adhered to in Ghana, for the screening of PLHIV for tuberculosis. Such a strategy has been found to be cost effective [33] and would lead to treatment of both conditions thus improving outcome [34].

This study while looking at virological and immunological response to ART among this cohort, had the limitation of not assessing the level of adherence to ART among the partcipants and other factors like prescribing practice and commodity availability. Such information would have contributed important information to explain the level of response found. Despite these limitations, the study provide useful finding which can inform ART clinicians and policy makers on what might need to be done to help Ghana work towards the “90, 90, 90” targets particularly with respect to achieving virological suppression at 12 months on ART.

In this tertiary facility, there was good response to ART among clients, high virological suppression and immunological recovery hence low rates of change to second line ART regimen in this cohort studied. This is very encouraging for the national control programme and shows that with strict adherence to the national policy on HIV testing, management of positive clients and full implementation of the “Treat All” policy, Ghana could achieve, if nothing at all, the third “90, 90, 90” target by 2020.