Red blood cell folate as a risk factor for breast cancer among patients at a tertiary hospital in Uganda: a case control study.

BACKGROUND: Folate has been shown to play a complex but unclear role in carcinogenesis, with some studies showing that low folate intake protects against early carcinogenesis while high folate intake promotes advanced carcinogenesis. Other studies have shown that high folate is associated with decreased breast cancer risk and overall survival, yet others found no such association.This study therefore sought to determine the association between red blood folate levels and breast cancer among women seen at a tertiary Ugandan hospital. METHODS: A case control study was conducted where female patients with a histological diagnosis of breast cancer were recruited as cases, and females without cancer attending other surgical clinics as controls. Demographics and social behavior data were collected and 5 mls of blood drawn for laboratory testing of red blood cell (RBC) folate, serum vitamin B12 and RBC count. Ethical approval was obtained. RESULTS: In this study, a total of 145 women were recruited as 72 cases and 73 controls. The odds of having breast cancer among women with normal folate levels compared to those with low folate levels were 1.4 (95% CI 0.7 to 2.9) P = 0.290. Ninety participants (63%) had low RBC folate and 53 participants (37%) had normal RBC folate. Thirty five (45%) of the women from a rural setting had normal folate levels compared to 18(28%) women from an urban setting. CONCLUSIONS: There was no significant association found between RBC folate and breast cancer among this group of women in Uganda.

Development of phenotypic and genotypic resistance to antiretroviral therapy in the UNAIDS HIV Drug Access Initiative--Uganda.

OBJECTIVE: We describe phenotypic drug resistance, response to therapy, and genotypic mutations among HIV-infected patients in Uganda taking antiretroviral medications for > or = 90 days who had a viral load > or = 1000 copies/ml. METHODS: HIV-1 group and subtype, virologic and immunologic responses to antiretroviral therapy, phenotypic resistance to antiretroviral drugs, and associated genotypic mutations among patients at three treatment centers in Uganda between June 1999 and August 2000 were assessed. Therapy was two nucleoside reverse transcriptase inhibitors (NRTIs) or highly active antiretroviral therapy (HAART). RESULTS: All HIV identified was HIV-1, group M, subtypes A, C, and D. Sixty-one (65%) of 94 patients with a phenotypic resistance result had evidence of phenotypic resistance including resistance to a NRTI for 51 of 92 (55%) taking NRTIs, to a non-nucleoside reverse transcriptase inhibitor (NNRTI) for nine of 16 (56%) taking NNRTIs, and to a protease inhibitor (PI) for eight of 37 (22%) taking PIs. At the time of the first specimen with resistance, the median change from baseline viral load was -0.56 log copies/ml [interquartile range (IQR), -1.47 to +0.29] and CD4+ cell count was +35 x 10(6) cells/l (IQR, -18 to +87). Genotypic resistance mutations, matched with phenotypic resistance assay results and drug history, were generally consistent with those seen for HIV-1, group M, subtype B infections in industrialized countries. CONCLUSION: Initial phenotypic resistance and corresponding genotypic mutations among patients treated in Uganda were similar to those with subtype B infections in North America and Europe. These data support policies that promote the use of HAART regimens against HIV-1, group M, non-B subtypes in a manner consistent with that used for subtype B infections.

Assessment of a pilot antiretroviral drug therapy programme in Uganda: patients' response, survival, and drug resistance.

BACKGROUND: Little is known about how to implement antiretroviral treatment programmes in resource-limited countries. We assessed the UNAIDS/Uganda Ministry of Health HIV Drug Access Initiative--one of the first pilot antiretroviral programmes in Africa--in which patients paid for their medications at negotiated reduced prices. METHODS: We assessed patients' clinical and laboratory information from August, 1998, to July, 2000, from three of the five accredited treatment centres in Uganda, and tested a subset of specimens for phenotypic drug resistance. FINDINGS: 912 patients presented for care at five treatment centres. We assessed the care of 476 patients at three centres, of whom 399 started antiretroviral therapy. 204 (51%) received highly active antiretroviral therapy (HAART), 189 (47%) dual nucleoside reverse transcriptase inhibitors (2NRTI), and six (2%) NRTI monotherapy. Median baseline CD4 cell counts were 73 cells/microL (IQR 15-187); viral load was 193817 copies/mL (37013-651 716). The probability of remaining alive and in care was 0.63 (95% CI 0.58-0.67) at 6 months and 0.49 (0.43-0.55) at 1 year. Patients receiving HAART had greater virological responses than those receiving 2NRTI. Cox's proportional hazards models adjusted for viral load and regimen showed that a CD4 cell count of less than 50 cells/microL (vs 50 cells/microL or more) was strongly associated with death (hazard ratio 2.93 [1.51-5.68], p=0.001). Among 82 patients with a viral load of more than 1000 copies/mL more than 90 days into therapy, phenotypic resistance to NRTIs was found for 47 (57%): 29 of 37 (78%) who never received HAART versus 18 of 45 (40%) who received HAART (p=0.0005). INTERPRETATION: This pilot programme successfully expanded access to antiretroviral drugs in Uganda. Identification and treatment of patients earlier in the course of their illness and increased use of HAART could improve probability of survival and decrease drug resistance.