From HIV infection to therapeutic response: a population-based longitudinal HIV cascade-of-care study in KwaZulu-Natal, South Africa

Abstract

Background: Standard approaches to estimation of losses in the HIV cascade of care are typically cross-sectional and do not include the population stages before linkage to clinical care. We used indiviual-level longitudinal cascade data, transition by transition, including population stages, both to identify the health-system losses in the cascade and to show the differences in inference between standard methods and the longitudinal approach.

Methods: We used non-parametric survival analysis to estimate a longitudinal HIV care cascade for a large population of people with HIV residing in rural KwaZulu-Natal, South Africa. We linked data from a longitudinal population health surveillance (which is maintained by the Africa Health Research Institute) with patient records from the local public-sector HIV treatment programme (contained in an electronic clinical HIV treatment and care database, ARTemis). We followed up all people who had been newly detected as having HIV between Jan 1, 2006, and Dec 31, 2011, across six cascade stages: three population stages (first positive HIV test, HIV status knowledge, and linkage to care) and three clinical stages (eligibility for antiretroviral therapy [ART], initiation of ART, and therapeutic response). We compared our estimates to cross-sectional cascades in the same population. We estimated the cumulative incidence of reaching a particular cascade stage at a specific time with Kaplan-Meier survival analysis.

Findings: Our population consisted of 5205 individuals with HIV who were followed up for 24 031 person-years. We recorded 598 deaths. 4539 individuals gained knowledge of their positive HIV status, 2818 were linked to care, 2151 became eligible for ART, 1839 began ART, and 1456 had successful responses to therapy. We used Kaplan-Meier survival analysis to adjust for censorship due to the end of data collection, and found that 8 years after testing positive in the population health surveillance, 16% had died. Among living patients, 82% knew their HIV status, 45% were linked to care, 39% were eligible for ART, 35% initiated ART, and 33% had reached therapeutic response. Median times to transition for these cascade stages were 52 months, 52 months, 20 months, 3 months, and 9 months, respectively. Compared with the population stages in the cascade, the transitions across the clinical stages were fast. Over calendar time, rates of linkage to care have decreased and patients presenting for the first time for care were, on average, healthier.

Interpretation: HIV programmes should focus on linkage to care as the most important bottleneck in the cascade. Cascade estimation should be longitudinal rather than cross-sectional and start with the population stages preceding clinical care.

Funding: Wellcome Trust, PEPFAR.

Figure 1. Kaplan-Meier graphs of longitudinal cascade vs annual cross-sectional cascades

Bars represent cross-sectional cascades generated on the basis of the last known stage of cascade progression on Dec 31 of each year. The red lines show the percentage of individuals reaching each stage up to 8 years after first testing positive for HIV. 95% CIs from of the Kaplan-Meier estimates are shown as brackets on the red lines. ART=antiretroviral therapy.

Figure 2. Transition to each stage by year—single state transitions

n=5205. Columns from left to right represent cascade stage transitions; rows from top to bottom show the years in which the entry transition event occurred. For example, the chart in the fourth column, second row, is the transition from “eligible for ART” to “initiated ART” for patients who became eligible for ART between 2008 and 2009 among those who had not yet initiated ART, for up to 4 years after reaching eligibility for ART. ART=antiretroviral therapy.

Figure 3. Transition to each stage by year, including entrance and exit stages, retention, and mortality

n=5205. The intercept in this figure shows the percentage of people who have already transitioned across subsequent cascade stages the first time they are detected in the denominator of a particular cascade stage. These intercepts thus represent the percentages of people who skip cascade stages or simultaneously transition across several stages. Each blue-shaded striation represents the cumulative incidence of reaching a cascade stage subsequent to the one that is represented by thick black lines in each panel of this figure. The percentage of people who have had a given number of additional clinic visits before transitioning is shown in green—the darker the shade of green, the more clinic visits. The cumulative incidence of death before the next transition is shown in pink, and the white area represents the proportion of people at each timepoint who are alive, have not made any additional clinic visits, and have not transitioned to a subsequent cascade stage. ART=antiretroviral therapy.