Utility of routine viral load, CD4 count and clinical monitoring among HIV-positive adults in rural Uganda
Polly Clayden, HIV i-Base
In an oral presentation, Alex Coutinho from TASO and Infectious Disease Institute, Kampala, Uganda presented findings from a randomised trial to evaluate the utility of laboratory vs clinical monitoring in rural Uganda.
This study was part of the Home Based AIDS Care (HBAC) programme for people with HIV, in which ART is provided to all eligible household members. In this programme lay workers delivered ART to participants’ homes each week and there were no scheduled clinic visits after enrollment.
HIV-positive adults with a CD4 count of <250 cells/mm3 or World Health Organisation (WHO) stage 3 or 4 received ART and were randomised to 1 of 3 monitoring groups: arm A, clinical monitoring and quarterly CD4 cell counts and viral loads; arm B, clinical monitoring and quarterly CD4 cell counts; or arm C, clinical monitoring alone.
Participants received NVP+3TC+d4T (EFV if receiving TB treatment) for first-line. Second-line could include LPV/r, ddI, AZT and TDF.
Lay workers collected data on illness and mortality, and referred participants to the study clinic for care. Quarterly CD4 cell counts and viral loads were performed for all participants. Clinicians received results as described in the study protocol.
Clinical failure was defined as, unintentional weight loss of >10%, CDC category 4 illness, diarrhea or fever for >1 month or new or recurrent oral, oesophageal or vaginal candiasis.
In this study 1116 ART-naïve participants were randomised and 1094 started ART, their median baseline CD4 cell count was 130 cells/mm3. The median follow-up was 3 years.
From the time of randomisation, there were 126 deaths (11.2%) and 148 new AIDS-defining illnesses; 47% of deaths and 57% of AIDS-defining illnesses occurred in the first three months of receiving ART. 61 (5.8%) of participants had virologic failure (defined as 2 consecutive viral loads >500 copies/mL) after the first 6 months of ART. 28 (2.7%) of participants changed to second line drugs.
The investigators found, in an intent-to-treat analysis from the date of starting ART, adjusting for age, sex, baseline CD4 count, viral load, body mass index, and Center for Epidemiologic Studies Depression Scale (CESD) score, the rate to new AIDS-defining event or death was higher in arm C than arm A (HR 1.88, p=0.002) or B (HR 1.47, p=0.047). They found no difference between arms B and A (HR 1.28, p=0.26). The study had 80% power to detect a rate ratio of 1.75 at p<0.05.
Although overall mortality in arm C during the 3 years of ART was low (13%), there was a non-significant trend towards higher mortality between arm C and arms A (HR 1.58, p=0.07) and B (HR 1.38, p=0.18). There was no difference in mortality between arms B and A (HR 1.14, p=0.6).
When the investigators looked at specific disease morbidity they found the incidence risk ratio (IRR) for TB, PCP, crypotoccal diseases and KS was significant for arm C vs A, across all four diseases: 1.7 (p=0.045), 8.7 (p=0.01), 2.3 (p=0.04) and 3.3 (p=0.07) respectively. For arm C vs B the IRR was significant for all but KS: 1.7 (p=0.045), 17.2 (p=0.009), 3.1 (p=0.013) and 1.6 (p=0.39) respectively.
Similar numbers of participants experienced virologic failure in all three arms, A:16, B:26 and C:19, and this was associated with increased severe morbidity or mortality (18% vs 10%, p=0.049). Overall 90% of participants had an undetectable viral load at one year. Of those participants experiencing virologic failure, 28 switched to second line regimens: 7/16, 4/26 and 2/19 in Arms A, B and C respectively. The total number of participants that switched in each arm were, 7, 4 and 17, of these 7, 4 and 2 switched to second line with detectable viral load in Arms A, B and C respectively.
Dr Coutinho noted that in Arm C,”15 people were substituted on clinical grounds even though they did not have a detectable viral load.”
He suggested that arms A and B did better not just because of the earlier switch (only <50% with viral load <500 copies/mL changed to second line drugs the remainder of the participants achieved subsequent suppression after adherence interventions), but using laboratory monitoring made it possible to identify problems with adherence before the occurrence of severe morbidity or mortality. “Clinical criteria were poorly sensitive and poorly specific to detect adherence challenges”, he explained.
He concluded: “Clinical monitoring alone was associated with increased rate of new AIDS-defining events and a trend towards increased mortality.” This study showed no benefit to adding quarterly viral load measurements to CD4 counts in the first three years of ART.
“However there is need to determine long term outcomes and cost effectiveness of CD4 and viral load monitoring”, he added.
This study was interesting but hard to interpret and like the Phillips et al study summarised above highlights the need for more data particularly the anticipated results from DART.
Alex Coutinho et al, Mermin J, J Ekwaru J et al. Utility of Routine viral load, CD4 cell count, and clinical monitoring among HIV-infected adults in Uganda: A randomised trial. Oral abstract 125