Heterogeneity in outcomes of treated HIV-positive patients in Europe and North America: relation with patient and cohort characteristics

Abstract

Background: HIV cohort collaborations, which pool data from diverse patient cohorts, have provided key insights into outcomes of antiretroviral therapy (ART). However, the extent of, and reasons for, between-cohort heterogeneity in rates of AIDS and mortality are unclear.

Methods: We obtained data on adult HIV-positive patients who started ART from 1998 without a previous AIDS diagnosis from 17 cohorts in North America and Europe. Patients were followed up from 1 month to 2 years after starting ART. We examined between-cohort heterogeneity in crude and adjusted (age, sex, HIV transmission risk, year, CD4 count and HIV-1 RNA at start of ART) rates of AIDS and mortality using random-effects meta-analysis and meta-regression.

Results: During 61 520 person-years, 754/38 706 (1.9%) patients died and 1890 (4.9%) progressed to AIDS. Between-cohort variance in mortality rates was reduced from 0.84 to 0.24 (0.73 to 0.28 for AIDS rates) after adjustment for patient characteristics. Adjusted mortality rates were inversely associated with cohorts' estimated completeness of death ascertainment [excellent: 96-100%, good: 90-95%, average: 75-89%; mortality rate ratio 0.66 (95% confidence interval 0.46-0.94) per category]. Mortality rate ratios comparing Europe with North America were 0.42 (0.31-0.57) before and 0.47 (0.30-0.73) after adjusting for completeness of ascertainment.

Conclusions: Heterogeneity between settings in outcomes of HIV treatment has implications for collaborative analyses, policy and clinical care. Estimated mortality rates may require adjustment for completeness of ascertainment. Higher mortality rate in North American, compared with European, cohorts was not fully explained by completeness of ascertainment and may be because of the inclusion of more socially marginalized patients with higher mortality risk.

Figure 1

Crude rates (per 1000 person-years) of AIDS and all cause mortality by cohort, average rate estimated during the period from 31 days to 2 years after start of ART. The size of the squares represents the weight assigned to each study in the meta-analysis and is proportional to the number of events in that study (whiskers show 95% CI). τ² is the between-cohort variance in the rate

Figure 2

Adjusted rates (per 1000 person-years) of AIDS and all cause mortality by cohort, average rate estimated during the period from 30 days to 2 years after start of ART. Adjusted for CD4 cell count (100–199) cells/mm³, log HIV-1 RNA (4–4.99) log copies/ml, age (30–44 years), sex-risk group (MSM), year of starting ART (2000–03)

Figure 3

Association of cohort-specific death rate (adjusted for patient characteristics) with ascertainment of death category. Circle sizes represent the precision of each cohort-specific estimate (the inverse of within-cohort variance), yellow denotes Canadian, blue USA and green European cohorts. τ² = 0.11 (from 0.84)