Hawkins C, Achenbach C, Fryda W, Ngare D, Murphy R. Antiretroviral durability and tolerability in HIV-infected adults living in urban Kenya. J Acquir Immune Defic Syndr 2007 Jul 1;45(3):304-310.
To investigate outcomes of antiretroviral therapy (ART), and the durability and tolerability of first-line regimens in HIV-infected adults in Nairobi, Kenya.
This was a longitudinal observational study of clinical, immunologic and treatment parameters among HIV-infected adults initiating ART.
The study took place at St. Mary's Mission Hospital in Nairobi, Kenya from September 2004 through August 2006. The hospital has an HIV program offering basic HIV care to local residents since 2002, and largely funded through PEPFAR.
Study participants included all HIV-infected patients naive to ART who presented between September 2004 and August 2006. Pregnant women, persons <18 years old, and those who didn't follow up were excluded from analysis. A total of 1286 HIV-infected patients were evaluated: median age was 36 yrs, 59% were female, 77% had a baseline CD4 count ≤200 cells/mm3, and 60% were from Nairobi.
There was no intervention in this observational cohort study. Most (62%) of treatment regimens were stavudine, lamivudine and nevirapine (NVP); 37% of patients started a regimen with efavirenz instead of NVP; however, only two patients (0.2%) were initiated on zidovudine instead of stavudine.
The primary outcome was mean change in CD4 cell count, drug toxicity, switching, death, and loss to follow-up.
RESULTS: At baseline, 41% had an active or previous OI, and 34% had a history of TB.
Clinical and immunologic outcomes: Mean CD4 cell count, weight, and hemoglobin (Hbg) increased significantly during the 18 months of follow-up; the prevalence of HIV-related symptoms and new OIs decreased over time. However, 14% of individuals developed new OIs after a median of 50 days on ART. Having a baseline CD4 count of ≤100 cells/mm3 was the only significant predictor of developing a new OI. Fourteen deaths (13 among men), occurred, with a mean time from baseline to death of 139 days.
Antiretroviral duration and modifications: The median duration of ART was 350 days (range: 1-722 days); more than half (54%) of patients switched at least one drug. Most switches were within ART class and the most common reason was toxicity (41%). The median time on ART before switching was 80 days. Independent predictors of switching included baseline CD4≤100 cells/µL (Hazard Ratio (HR)=1.2) and AIDS-related symptoms at baseline (HR=1.59). Switching therapy was an independent predictor of developing a new OI, clinical toxicity, and withdrawal from the program.
Antiretroviral clinical toxicity: Nearly 27% of patients experienced clinical toxicity, primarily neuropathy, which was reported by 21% of all patients. The median time to development of toxicity was 158 days. Baseline CD4 count and age were the only significant predictors of toxicity.
Program withdrawal: Nearly 40% of the patients who started ART withdrew from the program (median time of 118 days); 85% of these were lost to follow-up. Significant predictors of program withdrawal were the presence of AIDS symptoms at baseline (p<0.01) and being unmarried (p<0.01).
The authors conclude that their findings support the ongoing feasibility of ART rollout in resource-limited settings, but that efforts are needed to maximize ART durability by minimizing the number of patients switching therapy or withdrawing from programs. To address these issues, the authors suggest that more tolerable first-line ART be used, that ART remain free and available, and that alternatives regimens be considered when treating TB co-infection. The authors also highlight the limitations of using a passive reporting system to follow patients who leave or transfer to another program.
According to the relevant aspects of the Newcastle-Ottawa criteria for evaluating the quality of longitudinal observational studies, this study was of high quality. However, the authors note that the study was limited by selection bias because of its observational design, omissions in clinical data that were used for analysis, and not having a comparison set of records to confirm clinical and pharmaceutical data.
The results presented here are consistent with other studies that have demonstrated significant improvements in clinical parameters following initiation of ART in resource-limited settings.(1) However, the proportion of patients who switched drugs generally exceeds that which has been reported elsewhere.(2,3,4) Other studies also support the result that switching ART was a significant predictor for development of toxicity.(5)
Despite the promising clinical and immunological outcomes resulting from ART rollout, attention needs to be paid to the fact that a large proportion of patients may require changes in drugs due to toxicity, virologic failure, and interaction with TB treatment, the most common OI. Consideration of the use of better-tolerated first-line regimens needs to be made. The short time period between drug initiation and development of new OIs indicates that OIs could have been a result of immune reconstitution, pre-existing infection, or insensitive TB screening. These issues are likely due to the relatively late stage at which patients present for treatment. The high rate of loss to follow-up is particularly concerning and systems to prevent this, or ensure transfer to another program, need to be developed.
- Desclaux A, Ciss M, Taverne B, Sow PS, Egrot M, Faye MA, et al. Access to antiretroviral drugs and AIDS management in Senegal. AIDS 2003 Jul;17 Suppl 3:S95-101.
- Laurent C, Ngom Gueye NF, Ndour CT, Gueye PM, Diouf M, et al. Long-term benefits of highly active antiretroviral therapy in Senegalese HIV-1-infected adults. J Acquir Immune Defic Syndr 2005 Jan 1;38(1):14-7.
- Braitstein P, Brinkhof MW, Dabis F, Schechter M, Boulle A, Miotti P, Wood R, et al. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet 2006 Mar 11;367(9513):817-24.
- Forna F, Liechty CA, Solberg P, Asiimwe F, Were W, Mermin J, et al. Clinical toxicity of highly active antiretroviral therapy in a home-based AIDS care program in rural Uganda. J Acquir Immune Defic Syndr 2007 Apr 1;44(4):456-62.
- Dieleman JP, Jambroes M, Gyssens IC, Sturkenboom MC, Stricker BH, Mulder WM, et al. Determinants of recurrent toxicity-driven switches of highly active antiretroviral therapy. The ATHENA cohort. AIDS 2002 Mar 29;16(5):737-45.