Missed appointments in first six months of HIV treatment associated with poorer outcomes

Missing multiple clinic appointments soon after starting HIV therapy is associated with poor immunological and virological responses, and an increased risk of death, South African investigators report in the Journal of the International AIDS Society.

They found that patients who failed to attend their clinic on two or more occasions in the six months after starting treatment had generally poorer outcomes than those who turned up for all their appointments.

“Missing visits early is a marker for those who will have poorer outcomes even if returning to care,” comment the investigators.

At the end of 2008, over five million people in resource-limited settings were being treated with anti-HIV drugs.

“Initiating this many patients onto care in such a short time is a remarkable achievement, but not without its challenges,” write the researchers. Mortality and loss-to-follow-up rates are high in many countries, and keeping patients in care can be difficult.

Investigators at the Themba Lethu Clinic in Johannesburg wanted to see how many of their patients missed appointments in the six months after starting antiretroviral therapy. Their patients’ medical records were monitored to see if missing appointments was associated with immunologic and virologic outcomes after six months. The relationship between clinic attendance and mortality or loss to follow-up over twelve months was also investigated.

The study was retrospective and included 4476 individuals who started therapy between April 2004 and August 2008. All were aged over 18 and were starting HIV treatment for the first time. Their median baseline CD4 cell count was just 76 cells/mm³, 63% were women, and 89% were treated with fixed-dose d4T/3TC/efavirenz.

Appointments to collect antiretroviral drugs were scheduled at monthly intervals, and patients were also supposed to attend three medical appointments.

Overall, 65% of patients attended all their appointment, 26% missed one appointment, 7% missed two, and 2% failed to attend on three or more occasions.

“We identified strong independent predictors of missing a medical or ARV visit,” note the investigators. These included being a man (medical visits, adjusted risk ratio [ARR] = 1.16; 95% CI, 1.05 to 1.28;  ARV pick up, ARR = 1.15; 95% CI, 1.15 to 1.28) and treatment with nevirapine (medical visits, ARR = 1.18; 95% CI, 1.10 to 1.40).

Missing three or more visits was significantly associated with a poorer CD4 cell response (increase below 50 cells/mm³) after six months (RR = 2.3; 95% CI, 1.4 to 3.8).

In addition patients who missed two or three or more visits were significantly less likely to have a viral load below 400 copies/ml at this time.

Patients who missed two medical appointments doubled their risk of death (ARR = 2.06; 95% CI, 1.00 to 2.06), and missing three or more antiretroviral pick-ups was associated with an eight-fold increase in the risk of mortality (ARR = 8.15; 95% CI, 1.97-33.7).

The researchers suggest that failure to collect therapy could indicate poor treatment adherence. They also suggest missing medical appointments meant that opportunistic infections and other serious health problems were not being diagnosed.

Missing early appointments also increased the risk of being lost to follow-up significantly.

“Documenting the amount of missed visits early on treatment is crucial because of its potential implications for poorer treatment outcomes,” argue the authors. They note, “in our study, more than 35% of patients…failed to attend at least one clinic visit in the first six months of treatment.”

They conclude “our findings suggest that targeting those who miss visits early on in treatment could have benefits in terms of longer term mortality reductions. Future studies need to focus on identifying the barriers to adhering to a visit schedule s that interventions and support services can be directed to those at risk.”