Long term outcomes of antiretroviral therapy in a large HIV/AIDS care clinic in urban South Africa: a prospective cohort study

Abstract

Background: Clinical, immunologic and virologic outcomes at large HIV/AIDS care clinics in resource poor settings are poorly described beyond the first year of highly active antiretroviral treatment (HAART). We aimed to prospectively evaluate long-term treatment outcomes at a large scale HIV/AIDS care clinic in South Africa.

Methods: Cohort study of patients initiating HAART between April 1, 2004 and March 13, 2007, and followed up until April 1, 2008 at a public HIV/AIDS care clinic in Johannesburg, South Africa. We performed time to event analysis on key treatment outcomes and program impact parameters including mortality, retention in care, CD4 count gain, virologic success and first line regimen durability.

Results: 7583 HIV-infected patients initiated care and contributed to 161,000 person months follow up. Overall mortality rate was low (2.9 deaths per 100 person years, 95% CI 2.6-3.2), but high in the first three months of HAART (8.4 per 100 person years, 95% CI 7.2-9.9). Long-term on-site retention in care was relatively high (74.4% at 4 years, 95%CI 73.2-75.6). CD4 count was above 200 cells/mm(3 )after 6 months of treatment in almost all patients. By the fourth year of HAART, the majority (59.6%, 95%CI 57.8-61.4) of patients had at least one first line drug (mainly stavudine) substituted. Women were twice as likely to experience drug substitution (OR 1.97, 95% CI 1.80-2.16). By 6 months of HAART, 90.8% suppressed virus below 400 copies. Among those with initial viral suppression, 9.4% (95% CI 8.5-10.3%) had viral rebound within one year of viral suppression, 16.8% (95% CI 15.5-18.1) within 2 years, and 20.6% (95% CI 18.9-22.4) within 3 years of initial suppression. Only 10% of women and 13% of men initiated second line HAART.

Conclusion: Despite advanced disease presentation and a very large-scale program, high quality care was achieved as indicated by good long-term clinical, immunologic and virologic outcomes and a low rate of second line HAART initiation. High rates of single drug substitution suggest that the public health approach to HAART could be further improved by the use of a more durable first line regimen.

Figure 1

Kaplan-Meier curves of survival by CD4 count by time since HAART initiation. Note that the scale of the y-axis starts at 0.75 for readability.

Figure 2

Kaplan-Meier curves of lost to follow-up by CD4 count by time since HAART initiation. Patients were categorized as lost to follow-up if more than three months late for a scheduled visit, and if the tracing team was unable to gain information. Note that the scale of the y-axis starts at 0.75 for readability.

Figure 3

Kaplan-Meier estimates of viral rebound among patients with initial viral suppression. Initial virologic success is defined as viral load ≤ 400 copies/ml within six months of HAART initiation. Viral rebound is defined as two consecutive (or one if no additional measurement was available) viral load measurements greater than 400 copies/ml, or one viral load greater than 5000 among patients with initial virologic success.

Figure 4

Kaplan Meier estimates of time to first change of any kind to initial HAART regimen, separated by gender Male or Female.

Figure 5

Kaplan Meier estimates of first line regimen substitutions during first 4 years of HAART. AZT, zidovudine; NVP, nevirapine; EFZ, efavirenz; d4T, stavudine.

Figure 6

Kaplan Meier estimates of time to initiation of second-line HAART Regimen, separated by gender male or female. Majority of patients (87%) were switched to second line following documented virologic failure.