PAPER: Time From Human Immunodeficiency Virus Seroconversion to Reaching CD41 Cell Count Thresholds ,200, ,350, and ,500 Cells/mm3: Assessment of Need Following Changes in Treatment Guidelines

Time From Human Immunodeficiency Virus Seroconversion to Reaching CD41 Cell Count Thresholds ,200, ,350, and ,500 Cells/mm3: Assessment of Need Following Changes in 

Treatment Guidelines

Sara Lodi,1 Andrew Phillips,2 Giota Touloumi,3 Ronald Geskus,4 Laurence Meyer,5 Rodolphe Thie ́ baut,6 Nikos Pantazis,3 Julia del Amo,7 Anne M. Johnson,2 Abdel Babiker,1 and Kholoud Porter1 on behalf of the CASCADE Collaboration in EuroCoorda

Reference:
Lodi, S., Phillips, A., Touloumi, G., Geskus, R., Meyer, L., Thiébaut, R., ... & Porter, K. (2011). Time from human immunodeficiency virus seroconversion to reaching CD4+ cell count thresholds< 200,< 350, and< 500 cells/mm3: assessment of need following changes in treatment guidelines. Clinical infectious diseases, 53(8), 817-825.

Background. Recent updates of human immunodeficiency virus (HIV) treatment guidelines have raised the CD41 cell count thresholds for antiretroviral therapy initiation from 350 to 500 cells/mm3 in the United States and from 200 to 350 cells/mm3 in mid- and low-income countries. Robust data of time from HIV seroconversion to CD41 cell counts of 200, 350, and 500 cells/mm3 are lacking but are needed to inform health care planners of the likely impact and cost effectiveness of these and possible future changes in CD41 cell count initiation threshold.
Methods. Using Concerted Action on Seroconversion to AIDS and Death in Europe data from individuals with well-estimated dates of HIV seroconversion, we fitted mixed models on the square root of CD41 cell counts measured before combined antiretroviral therapy (cART) initiation. Restricting analyses to adults (age .16 years), we predicted time between seroconversion and CD41 cell count ,200, ,350, and ,500 cells/mm3 as well as CD41 cell count distribution and proportions reaching these thresholds at 1, 2, and 5 years after seroconversion.
Results. Median (interquartile range [IQR]) follow-up for the 18 495 eligible individuals from seroconversion while cART-free was 3.7 years (1.5, 7). Most of the subjects were male (78%), had a median age at seroconversion of 30 years (IQR, 25–37 years), and were infected through sex between men (55%). Estimated median times (95% confidence interval [CI]) from seroconversion to CD41 cell count ,500, ,350, and ,200 cells/mm3 were 1.19 (95% CI, 1.12–1.26), 4.19 (95% CI, 4.09–4.28), and 7.93 (95% CI, 7.76–8.09) years, respectively. Almost half of infected individuals would require treatment within 1 year of seroconversion for guidelines recommending its initiation at 500 cells/mm3, compared with 26% and 9% for guidelines recommending initiation at 350 and 200 cells/mm3, respectively.
Conclusions. These data suggest substantial increases in the number of individuals who require treatment and call for early HIV testing.

Discussion
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Using a large dataset of 18,495 individuals with well-estimated dates of HIV seroconversion, we estimated that CD41 cell counts ,500, ,350, and ,200 cells/mm3 are reached, on av- erage, at approximately 1, 4, and 8 years, respectively. We also estimated that, of 100 newly infected individuals, 48, on average, would require treatment within 1 year after seroconversion for guidelines indicating initiation at 500 cells/mm3, compared with 27 and 9 individuals for guidelines indicating initiation at 350 and 200 cells/mm3, respectively. At 5 years, 55 of these individuals are expected to reach CD41 cell counts below

350 cells/mm3, compared with 33 for CD41 cell counts below 200 cells/mm3. 

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To the best of our knowledge, this is the largest study to estimate the time between seroconversion and these 3 CD41 cell count thresholds for cART initiation.

In our study, women reached the CD41 cell count thresholds for cART initiation 2–11 months later than did men of the same risk group, age group, and cal- endar period of seroconversion. It has been suggested that women seroconvert, develop AIDS, and die at a higher CD41 cell count than do men [25]. T

Conclusion

Our findings provide strong support for public health cam- paigns to encourage early HIV infection diagnosis and testing, especially in targeted populations at an increased risk of HIV infection, enabling those infected to initiate therapy at the op- timum time. Given the substantial increase in the number of individuals eligible for treatment as a result of the latest changes in guidelines, it is crucial that the choice of the CD41 cell count threshold for cART initiation is supported by evidence of benefit from randomized controlled trials and appropriate cost-effectiveness considerations.