Treatment of HIV-1 infection with highly active antiretroviral therapy (HAART), even with major price reductions, will probably remain unaffordable for most people infected with HIV-1 who live in less-developed countries.

Alternative options that are relevant to resource-poor settings should therefore be investigated. Hydroxychloroquine and its analogue chloroquine could be useful as cheaper components of combination antiretroviral therapy. The authors of the current study did a pilot study to assess the safety, tolerability, and efficacy of hydroxychloroquine, hydroxycarbamide, and didanosine as an economical combination therapy for HIV-1 infection.

The researchers recruited 22 symptom-free adults who were infected with HIV-1 and who had not had previous antiretroviral treatment. Patients had a plasma viral load of less than 100,000 copies/mL and a CD4 lymphocyte count of more than 150 cells/µL. Patients with known malignant disease, diabetes mellitus, psoriasis, peripheral neuropathy, retinal disease, glucose-6-phosphate dehydrogenase deficiency, and significant abnormal hematological or biochemical variables on screening blood tests were excluded. All patients took hydroxychloroquine (200 mg), hydroxycarbamide (500 mg), and didanosine (125-200 mg according to body weight) twice daily. A review of symptoms, physical and ophthalmological examination, measurement of full blood count, standard biochemical safety variables, viral load (Roche Amplicor assay), and CD4 count were done every 12 weeks. Viral loads below the limit of detection of the assay (400 copies/mL) were assigned a value of 200 copies/mL (2·3 log) to calculate the mean viral load change.

Twelve men and ten women with a mean age of 35 years participated. Six patients were withdrawn from the study because of non-compliance with medication (missed more than 2 weeks). Safety and tolerability were assessed in all enrolled patients up to week 48 or at time of withdrawal from the study, and efficacy was assessed in the 16 evaluable patients. The combination was well tolerated with only mild side effects reported, none of which resulted in discontinuation of treatment.

No patient developed peripheral neuropathy, retinopathy, or clinical pancreatitis, and the researchers recorded no serious clinical adverse events that were judged to be related to study medication. Eight (36 percent) of 22 patients had neutropeni, and there was increased amylase concentration in serum in six (27 percent).

Viral load was reduced significantly by a mean of 1·3 log10 copies/mL at week 12, and this reduction was sustained up to week 48. All 16 patients had viral loads below baseline, four had an undetectable viral load (<400 copies/mL), and 14 had a viral load of less than 3000 copies/mL at week 48. The percentage CD4 count increased significantly by a mean of 4.3 percent at week 12 and this was sustained up to week 48.

The low but detectable viral loads recorded raise the concern that resistance could develop early and the virus could rebound, but sustained activity of this combination at 48 weeks suggests that significant resistance did not develop. Indeed, the inverse relation between viral load nadir and time to rebound might not hold true for unconventional regimens.

The drug combination had only a modest effect on CD4 count. Although conventional HAART regimens usually achieve greater immune reconstitution, the clinical advantage arising from such reconstitution is uncertain in patients who start treatment with a CD4 count of more than 150 cells/µL and who take prophylaxis for Pneumocystis carinii pneumonia. Keeping CD4 counts at or above this level should be sufficient to avoid the morbidity and mortality associated with the major opportunistic infections.

The non-comparative design of this pilot study does not allow the researchers to determine the contribution made by hydroxychloroquine alone to the overall decrease in viral load achieved by the combination. A large randomized controlled trial, focusing on long-term durability, is needed to determine the contribution of hydroxychloroquine. The combination of hydroxychloroquine, hydroxycarbamide, and didanosine could be used in countries that have restricted resources. The drugs are all easy and cheap to make, and hydroxychloroquine and hydroxycarbamide can already be generically manufactured.

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