Ngs on KS mortality [8,25] and highlights the importance of early diagnosis and initiation of appropriate treatment for HIV-infected subjects with KS at every stage of HIV infection and treatment. We also note that the KS group were more likely to have a diagnosis of tuberculosis at initiation of ART when compared to those without KS. Though TB is not diagnosed Title Loaded From File primarily by chest x-ray in these settings, the radiographic appearance of the nodular infiltrate associated with pulmonary KS could have been mistaken for TB in some cases. Pulmonary KS is associated with high rates of mortality and though all models were adjusted for diagnosis of TB at ART initiation, this may have contributed to the excess mortality noted in the KS group. Though the results were imprecise and lacked statistical significance, we note that the majority of estimates suggested those with KS were less likely to fail to suppress HIV viral load. It is possible that this reflects survivor bias in that those with KS who are also poorly adherent to treatment do not survive to have a viral load test done at the intervals described. Though we cannot make inferences from our results, if this effect were real, it might suggest better adherence among those surviving with KS possibly related to more intensive follow up and more frequent attendance at clinic visits for their KS related care. We did also note some immunologic differences. First, those with KS were roughly twice as likely to have a nadir CD4 count between 200 and 350 cells/ mm3 compared to those without KS. This is likely explained by the fact that KS (as a WHO stage 4-defining condition) was an indication for initiation of ART with CD4 count 200 cells/mm3 at a time when the ART eligibility criteria were otherwise ,200. Second, after initiation of ART, those with KS were less likely to increase their CD4 cell counts by 50 and 100 cells at 6 and 12 months on treatment respectively. The KS group also had a smaller mean increase in CD4 cell count at both time periods than those without KS though the actual Title Loaded From File difference in CD4 gain wasKaposi Sarcoma and ART in HIV-Positive PopulationTable 3. Immunologic and Virologic Outcomes at 6 and 12-months on ART stratified by KS status among 8,676 adult HIV-infected patients initiating ART in Cape Town and Johannesburg, South Africa.6-months Exposure Number with failure Crude RR (95 CI)` Adjusted{ RR (95 CI)`12-months Number with failure Crude RR (95 CI)` Adjusted{ RR (95 CI)`Immunologic failure*No KS KS 1565 (18.3 ) 29 (24.4 ) 1.0 1.33 (0.97?.83) 1.0 1.43 (0.99?.06) 1655 (23.3 ) 29 (29.9 ) 1.0 1.28 (0.94?.74) 1.0 1.20 (0.84?.73)Failure to suppress HIV viral load**No KS KS{642 (7.8 ) 14 (10.7 )1.0 1.37 (0.83?.26)1.0 0.82 (0.38?.79)714 (10.2 ) 7 (6.9 )1.0 0.67 (0.33?.38)1.0 0.25 (0.06?.00)Models adjusted for sex, baseline CD4 count, age, treatment site, tuberculosis at ART initiation, year of ART initiation. VL = viral load, RR = relative risk, CI = confidence interval, relative risk from a log-binomial regression model KS = Kaposi’s sarcoma, ART = antiretroviral therapy, *Failure to achieve a CD4 response defined as an increase of 50 cells/mm3 at 6 months and 100 cells/mm3 at 12 months. **Failure to suppress VL to ,400 copies/ml. doi:10.1371/journal.pone.0064392.t`small between the groups. This may be due to differences in disease stage at treatment initiation [30] or possibly related to the additional suppressive effect of chemotherapy on the KS patients’ immune system.Ngs on KS mortality [8,25] and highlights the importance of early diagnosis and initiation of appropriate treatment for HIV-infected subjects with KS at every stage of HIV infection and treatment. We also note that the KS group were more likely to have a diagnosis of tuberculosis at initiation of ART when compared to those without KS. Though TB is not diagnosed primarily by chest x-ray in these settings, the radiographic appearance of the nodular infiltrate associated with pulmonary KS could have been mistaken for TB in some cases. Pulmonary KS is associated with high rates of mortality and though all models were adjusted for diagnosis of TB at ART initiation, this may have contributed to the excess mortality noted in the KS group. Though the results were imprecise and lacked statistical significance, we note that the majority of estimates suggested those with KS were less likely to fail to suppress HIV viral load. It is possible that this reflects survivor bias in that those with KS who are also poorly adherent to treatment do not survive to have a viral load test done at the intervals described. Though we cannot make inferences from our results, if this effect were real, it might suggest better adherence among those surviving with KS possibly related to more intensive follow up and more frequent attendance at clinic visits for their KS related care. We did also note some immunologic differences. First, those with KS were roughly twice as likely to have a nadir CD4 count between 200 and 350 cells/ mm3 compared to those without KS. This is likely explained by the fact that KS (as a WHO stage 4-defining condition) was an indication for initiation of ART with CD4 count 200 cells/mm3 at a time when the ART eligibility criteria were otherwise ,200. Second, after initiation of ART, those with KS were less likely to increase their CD4 cell counts by 50 and 100 cells at 6 and 12 months on treatment respectively. The KS group also had a smaller mean increase in CD4 cell count at both time periods than those without KS though the actual difference in CD4 gain wasKaposi Sarcoma and ART in HIV-Positive PopulationTable 3. Immunologic and Virologic Outcomes at 6 and 12-months on ART stratified by KS status among 8,676 adult HIV-infected patients initiating ART in Cape Town and Johannesburg, South Africa.6-months Exposure Number with failure Crude RR (95 CI)` Adjusted{ RR (95 CI)`12-months Number with failure Crude RR (95 CI)` Adjusted{ RR (95 CI)`Immunologic failure*No KS KS 1565 (18.3 ) 29 (24.4 ) 1.0 1.33 (0.97?.83) 1.0 1.43 (0.99?.06) 1655 (23.3 ) 29 (29.9 ) 1.0 1.28 (0.94?.74) 1.0 1.20 (0.84?.73)Failure to suppress HIV viral load**No KS KS{642 (7.8 ) 14 (10.7 )1.0 1.37 (0.83?.26)1.0 0.82 (0.38?.79)714 (10.2 ) 7 (6.9 )1.0 0.67 (0.33?.38)1.0 0.25 (0.06?.00)Models adjusted for sex, baseline CD4 count, age, treatment site, tuberculosis at ART initiation, year of ART initiation. VL = viral load, RR = relative risk, CI = confidence interval, relative risk from a log-binomial regression model KS = Kaposi’s sarcoma, ART = antiretroviral therapy, *Failure to achieve a CD4 response defined as an increase of 50 cells/mm3 at 6 months and 100 cells/mm3 at 12 months. **Failure to suppress VL to ,400 copies/ml. doi:10.1371/journal.pone.0064392.t`small between the groups. This may be due to differences in disease stage at treatment initiation [30] or possibly related to the additional suppressive effect of chemotherapy on the KS patients’ immune system.
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