Date Published: April 3, 2018
Publisher: Public Library of Science
Author(s): Kimberly A. Powers, Matthew A. Price, Etienne Karita, Anatoli Kamali, William Kilembe, Susan Allen, Eric Hunter, Linda-Gail Bekker, Shabir Lakhi, Mubiana Inambao, Omu Anzala, Mary H. Latka, Patricia E. Fast, Jill Gilmour, Eduard J. Sanders, Cristian Apetrei.
Prompt identification of newly HIV-infected persons, particularly those who are most at risk of extended high viremia (EHV), allows important clinical and transmission prevention benefits. We sought to determine whether EHV could be predicted during early HIV infection (EHI) from clinical, demographic, and laboratory indicators in a large HIV-1 incidence study in Africa.
Adults acquiring HIV-1 infection were enrolled in an EHI study assessing acute retroviral syndrome (ARS) symptoms and viral dynamics.
Estimated date of infection (EDI) was based on a positive plasma viral load or p24 antigen test prior to seroconversion, or the mid-point between negative and positive serological tests. EHV was defined as mean untreated viral load ≥5 log10 copies/ml 130–330 days post-EDI. We used logistic regression to develop risk score algorithms for predicting EHV based on sex, age, number of ARS symptoms, and CD4 and viral load at diagnosis.
Models based on the full set of five predictors had excellent performance both in the full population (c-statistic = 0.80) and when confined to persons with each of three HIV-1 subtypes (c-statistic = 0.80–0.83 within subtypes A, C, and D). Reduced models containing only 2–4 predictors performed similarly. In a risk score algorithm based on the final full-population model, predictor scores were one for male sex and enrollment CD4<350 cells/mm3, and two for having enrollment viral load >4.9 log10 copies/ml. With a risk score cut-point of two, this algorithm was 85% sensitive (95% CI: 76%-91%) and 61% specific (55%-68%) in predicting EHV.
Simple risk score algorithms can reliably identify persons with EHI in sub-Saharan Africa who are likely to sustain high viral loads if treatment is delayed. These algorithms may be useful for prioritizing intensified efforts around care linkage and retention, treatment initiation, adherence support, and partner services to optimize clinical and prevention outcomes.
Antiretroviral therapy (ART) initiated early in HIV-1 infection preserves immune function , reduces adverse clinical outcomes [2–4], and prevents transmission . Recognizing these benefits, HIV treatment guidelines recommend ART initiation at diagnosis, regardless of CD4 count [5,6]. However, as of July 2017, only 60% of low- and middle-income countries had adopted the “Treat All” policy, and only 9% had implemented this approach in a majority of treatment sites . These lags in guideline implementation—combined with suboptimal care linkage among those who are ART-eligible at diagnosis [8, 9] and poor care retention both before  and after  ART initiation—result in substantial losses of both clinical and transmission prevention benefits.
Of 613 HIV-1 seroconverters enrolling in the EHI cohort, 422 (68.8%) enrolled and completed information on ARS symptoms ≤90 days after their EDI (Fig 1). Of these, 388 (91.9%) had at least one pre-ART viral load measurement (range = 1–5 measurements; mode = 2 measurements) between 130 and 330 days post-EDI, and were thus eligible for analysis. Approximately one-third (34.8%) of the eligible volunteers had HIV-1 subtype A, 43.8% subtype C, and 15.7% subtype D, with the remaining 5.7% comprising other subtypes (Table 1). Across subtypes, the median age among males and females was 30 and 28 years, respectively, and the majority (72.9%) of volunteers belonged to serodiscordant couples. A lower proportion of those with subtype A were female versus those with subtypes C and D, and although the age distribution in females was similar across subtypes, male volunteers with subtype A were appreciably younger than those with subtype C (but not D). Due to differences in at-risk source populations across research centers, serodiscordant couples were more prevalent among those with subtype C than with the other two subtypes, and men who have sex with men were more prevalent among those with subtype A. Overall, the median time between EDI and enrollment was 45 days, median number of ARS symptoms was 2, and median enrollment viral load was 4.9 log10 copies/ml. Time since EDI and enrollment viral load were similar across subtypes, but subtype A volunteers had a greater number of ARS symptoms than those with subtypes C and D (as previously reported in ). The proportions with CD4>350 and CD4>500 (83.1% and 54.3% overall, respectively) were similar across subtypes.
Rapid identification and treatment of newly HIV-infected persons can have important clinical and public health benefits, but many persons with EHI are likely to have CD4 counts above current ART initiation thresholds in many sub-Saharan African countries [6,7], and suboptimal linkage and retention are prevalent even among treatment-eligible persons [8–11]. The detrimental effects of delaying treatment are particularly great among newly infected persons who sustain high viral loads, allowing unmitigated transmission for months or years before treatment begins. To determine whether limited resources for linkage, retention, treatment, and partner services could be efficiently targeted toward EHI cases with the highest potential for onward transmission and clinical progression, we sought to develop predictive models and risk score algorithms for EHV based on previously identified correlates of sustained high viremia.