Table 2.

Summary of Hydroxyurea safety and efficacy in patients with HIV.

Study	Patients	Treatment	Effectiveness on HIV status	Adverse Effects
Lori et al¹⁵	57 HIV-infected CD4 count 250–500	Didanosine + hydroxyurea (500mg) Didanosine Treated for 24 weeks	Decrease in viral load greater in hydroxyurea treated group. No difference in the increase in CD4 count.	No major toxic event Minor bone marrow toxicity (did not warrant discontinuation of treatment)
Rutschmann et al¹⁶	144 HIV-infected CD4 count 200–500 HIV-1 RNA levels >1000	Hydroxyurea treated: Didanosine + stavudine +hydroxyurea (500mg BID) Placebo: didanosine + stavudine Treated for 24 weeks	First 12 weeks: hydroxyurea group had greater decrease in HIV-1 RNA levels.	Fatigue, neuropathies, neutropenia, thrombocytopenia. All resolved with discontinuation of treatment CD4 count had lesser increase in hydroxyurea treated group. CD8 count had lesser increase in hydroxyurea treated group
Havlir et al¹⁷	202 HIV-infected CD4 count >200 HIV RNA levels <200	Original group: indinavir + zidovudine + lamivudine New treatment (2 groups): Indinavir + didanosine + stavudine +/− hydroxyurea Treatment for median follow-up time of 40 weeks	Hydroxyurea treated group: 32% failed treatment (mostly due to drug toxicity) Placebo: 17.6% failed treatment Original group: 7.6% failed treatment	Pancreatitis (4 in hydroxyurea treated group, 3 in group without hydroxyurea). CD4 count drop in first 4 weeks of treatment with hydroxyurea.
Lafeuillade et al¹⁸	69 HIV-infected	Placebo: stavudine + didanosine + efavirenz + abacavir. Hydroxyurea (500mg BID) + placebo Hydroxyurea (500mg BID) + IL-2 + placebo Treated for 48 weeks.	Placebo: 25%, 20.8% reached HIV-1 RNA levels <200, <20 Hydroxyurea group: 59.1%, 54.5% reached HIV-1 RNA levels <200, <20 Hydroxyurea + IL-2 group: 56.5%, 47.8% reached HIV-1 RNA levels <200, <20	CD4 decreased in hydroxyurea treated group Lactic acidosis, peripheral neuropathy, LFT elevation. 2 patients from hydroxyurea treated group and 3 from hydroxyurea +IL-2 treated group required dose decrease due to cytopenia. No AIDS defining illnesses.
Frank et al¹⁹	134 HIV-infected CD4 count 200–700	Combination arm: Didanosine + hydroxyurea (1g or 1.5g/day) group Hydroxyurea (1 or 1.5g/day) group (didanosine added at week 4) Didanosine group (hydroxyurea added at week 12)	Didanosine group: 0.9 (week 8) and 1.1 (week 24) log10 decrease in HIV-1 RNA levels Combination arm: 1.9 (week 8) and 1.6 (week 24) log10 decrease in HIV-1 RNA levels Hydroxyurea group: 1.2 log10 decrease at week 24 CD4 counts increased slightly with combination arm while decreased in hydroxyurea group and didanosine group	Hydroxyurea 1.5g/day had more hematologic adverse events than hydroxyurea 1g/day and didanosine alone Longer exposure = increased hematologic AE
Malhotra el al²⁰	39 HIV-infected CD4 count >200 HIV-1 RNA <200 Treated for 24 weeks	Original group: indinavir + lamivudine + zidovudine New therapy: indinavir +didanosine + stavudine + placebo or hydroxyurea (600mg BID)	Placebo: 7% failure rate Hydroxyurea group: 27% failure rate Original group: 0% failure rate Markers of HIV activation between groups showed no difference.	Drug toxicity (unspecified) of 2/11 patients in hydroxyurea treated group. Hydroxyurea group: CD4 count had greater decline than other groups
Stebbing et al²¹	21 HIV-infected Failed HAART (zidovudine, stavudine, didanosine, lamivudine) HIV-1 RNA >5,000	Stavudine + didanosine Stavudine + didanosine + hydroxyurea (500mg BID) Treated for 12 weeks	Both groups had significant decrease in HIV-1 RNA levels, but hydroxyurea did not have added benefit.	Decrease in CD4 count in hydroxyurea treated group.