**2.1 Prevalence of immunological failure/immune reconstitution among HIV infected individuals on HAART**

Immune reconstitution is the immunological response of immune cells (mostly CD4+ T cells) due to initiation of HAART. The response is either success or failure. Previously conducted studies reported different rates of immunological failure among HIV infected individuals (**Table 1**).

The variation among the above studies might be explained due to the differences in patient adherence, differences to define immunological failure whereby some studies defined as the reduction in number of CD4 + T cell count to baseline or below, or persistently low CD4+ T cell count (below 100 cells/μL) [31] and others defined immunological failure as reduction in number of CD4+ T cell count to baseline or below severe immune suppression (CD4+ T cell count <200 cells/μL) [24, 25, 28, 30, 32, 33]. Other studies defined immunological failure as 50% decline of CD4+ T cells from treatment peak value [28, 34] or at least 30% decline from treatment peak value [28, 35].

Moreover, the prevalence of immunological failure can be expressed with person-years among the HIV patients on treatment. As per recent studies, the rate was 2.966 [22], 2.57 [36], 8.7 [37] and 8 [38] person-years. The variation among these reports might be due to the differences in treatment adherence and the presence of opportunistic infections (status of co-morbidity). Hence, the coverage of good adherence toward the HAART was one of the determining factors for immunological success. The likelihood of having good adherence of HAART increases the treatment success rate considering the results of previous studies (**Table 2**).


#### **Table 1.**

*Occurrence of immunological failure of HIV infected individuals on HAART.*

*Immunological and Virological Failure among Individuals on Highly-Active Antiretroviral… DOI: http://dx.doi.org/10.5772/intechopen.98593*


#### **Table 2.**

*Coverage of good treatment adherence of clients from different studies.*

Treatment adherence differs among studies due to differences in psychosocial support of relatives or the society to strictly adhere to the treatment guidelines, stigma, and lack of commitment to take medications so that HIV patients might drop themselves from on course ART treatment, perceived feeling of unwellness from medication, and scaring of treatment side effects [31, 40, 41].

Previously, baseline CD4+ T cell counts were playing an important role for an HIV patient to initiate HAART. The median baseline CD4+ T cell counts for an HIV infected individual to start HAART is explained below (**Table 3**). However, nowadays, the target is to test and treat regardless of their CD4+ T cell counts.

## **2.2 Associated factors of immunological failure among HIV infected individuals on HAART**

Poor adherence to HAART increased to experience failure in CD4+ T cell recovery [22, 26, 28, 33, 43]. This allows increased viral replication which in turn increases infection of new CD4+ T cells and ultimately depletion of immune cells [41]. Additionally, lower baseline CD4+ T cell count is one of the determining factors for increased immunological failure because immune recovery mostly depends on the number of baseline CD4+ T cell counts [22, 29, 38]. The timing of HAART initiation is important to optimize the CD4+ T cell immune response to medication [44].


#### **Table 3.**

*Median baseline CD4+ T cell counts of HIV infected individuals to initiate HAART as per previously published studies.*

#### *Current Perspectives on Viral Disease Outbreaks - Epidemiology, Detection and Control*


**Table 4.**

*Prevalence of virological failure of HAART among individuals infected with HIV.*

These reports may highlight that patients with low CD4+ T cell count have poor long term CD4+ T cell immune response [22].

TB/HIV co-infection worsen the rate of immunological failure [22, 25, 37, 45–48]. TB infection impairs cellular immune responses through MTB-induced apoptosis of CD4+ T cells which subsequently lead to depletion of CD4+ T cells [49]. Incidence of TB during the course of HAART decreased the likelihood of treatment adherence due to its high pill burden and side-effects [50]. Although the risk of acquiring TB remains elevated, much less is known about the effect of HAART on recurrent TB [51]. All in all, recurrences of TB are lower among HIV infected individuals with higher CD4+ T cell counts [52].

## **2.3 Occurrence of virological failure among HIV infected individuals on HAART**

Virological failure among individuals on HAART is defined as plasma viral load of the HIV infected individual is greater than 1000 RNA copies/ml based on two consecutive viral load measurements with adherence support [53]. The occurrence of virological failure of HAART among HIV infected individuals is reported below (**Table 4**).

The variation might be due to the differences in cutoff values of viral RNA copies per ml of plasma to consider virological failure [60, 63, 70], the duration of follow-up, differences of co-morbidity, variations on the treatment adherence of HAART, clinical/immunological failure [61, 71], perinatally infected [67], lower mean age [65] and shorter duration on HAART [66].

### **2.4 Associated factors of virological failure among HIV infected individuals on HAART**

Magnitude of virological failure of HAART is not the same for all HIV infected individuals. There are factors that affect the likelihood of virological failure like

*Immunological and Virological Failure among Individuals on Highly-Active Antiretroviral… DOI: http://dx.doi.org/10.5772/intechopen.98593*

malnourishment and overweight [22, 54, 72, 73]. Abnormal body mass index (BMI) is significantly correlated with decreased CD4+ T cell counts that increases viral load by progressing into the advanced stage of the disease [74, 75].

Moreover, the occurrence of virological failure is higher among TB co-infected individuals [54, 76, 77]. Concurrent HAART and TB treatment increases the rate of virological failure due to impaired treatment adherence and pharmacokinetics drug reactions. Hence, clients on HAART with active TB should be prioritized for viral load monitoring and follow-up. Moreover, to prevent incident TB during ART INH prophylaxis is recommended. Increased viral copies compromise immunity and negatively affect treatment by contributing to the double burden side effects of TB and HIV [78].

Failure for an immune-reconstitution increases the rate of virological failure [54, 79–81]. This leads to an increase in viral replication [22]. Hence, it is a surrogate marker for virological failure. During HAART, detecting and monitoring immunological response should also be emphasized to prevent drug resistance [22, 82].
