Browsing by Author "Mermin, Jonathan"

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Assessment of a Pilot Antiretroviral Drug Therapy Programme in Uganda: Patients' Response, Survival, and Drug Resistance
(Elsevier, 2002-07-06) Weidle, J Paul; Malamba, Samuel; Mwebaze, Raymond; Sozi, Catherine; Rukundo, Gideon; Downing, Robert; Hanson, Debra; Ochola, Dorothy; Mugyenyi, Peter; Mermin, Jonathan; Samb, Badara; Lackritz, Eve
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/μL (IQR 15–187); viral load was 193 817 copies/mL (37 013–651 716). 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/μL (vs 50 cells/μL 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.
Development of Phenotypic and Genotypic Resistance to Antiretroviral Therapy in the UNAIDS HIV Drug Access Initiative – Uganda
(Wolters Kluwer Health, Inc., 2003-07) Weidlea, J. Paul; Downingb, Robert; Sozic, Catherine; Mwebaze, Raymond; Rukundo, Gideon; Malamba, Samuel; Respessa, Richard; Hertogsf, Kurt; Larderg, Brendan; Ochola, Dorothy; Mermin, Jonathan; Badara Sambk, Badara; Lackritz, Eve
Objective: We describe phenotypic drug resistance, response to therapy, and geno-typic mutations among HIV-infected patients in Uganda taking antiretroviral medica-tions for ≥ 90 days who had a viral load ≥ 1000 copies/ml. Methods: HIV-1 group and subtype, virologic and immunologic responses to anti-retroviral therapy, phenotypic resistance to antiretroviral drugs, and associated geno-typic mutations among patients at three treatment centers in Uganda between June 1999 and August 2000 were assessed. Therapy was two nucleoside reverse tran-scriptase 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 × 106 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.
Long-Term Experience Providing Antiretroviral Drugs in a Fee-for-Service HIV Clinic in Uganda
(Wolters Kluwer Health, Inc., 2005-04-15) Kabugo, Charles; Bahendeka, Sylver; Mwebaze, Raymond; Malamba, Samuel; Katuntu, David; Downing, Robert; Mermin, Jonathan; Weidle, J. Paul
Objective: To describe the long-term experience of providing anti-retroviral (ARV) therapy, including CD4+ cell count and virologic response, at St. Francis Hospital, Nsambya, Uganda. Methods: The HIV clinic established in 1998 is a fee-for-service model where patients pay for ARVs. The care of patients who started ARVs from August 1, 1998 until October 31, 2000 was evaluated through December 31, 2002. Data were collected at the HIV clinic on standardized clinical forms. These patients had free CD4+ cell count and viral load testing performed at times determined by the physician. All persons who had ≥1 CD4+ cell count or viral load done ≥90 days after starting therapy were evaluated. Results: Three hundred twenty-one patients (49% women, 66% ARV naive, median age = 38 years, median CD4+ cell count = 79 cells/mm3, and median viral load = 249,489 copies/mL) attended the HIV clinic. Two hundred sixty-three (82%) patients returned at least once after the initial visit, of whom 54 (21%) had an interruption in therapy for >1 year. One hundred thirty-five patients were in care in 2002, 69 were known to have died (9 of whom died in 2002), and 68 were lost to follow-up. The probability of remaining alive and in care at 1 year was 0.56 (95% confidence interval [CI]: 0.50-0.61), 0.46 (95% CI: 0.41-0.51) at 2 years, 0.40 (95% CI: 0.34-0.45) at 3 years, and 0.35 (95% CI: 0.29-0.41) at 4 years. In an on-treatment analysis, the median CD4+ cell count increase during year 1 was +55 cells/mm3, +112 cells/mm3 during year 2, +142 cells/mm3 during year 3, and +131 cells/mm3 during year 4. The median log viral load change from baseline during year 1 was −1.4 copies/mL, −1.32 copies/mL during year 2, −1.9 copies/mL during year 3, and −1.51 copies/mL during year 4. Conclusions: This fee-for-service HIV clinic providing ARV treatment has successfully operated and managed patients for more than 4 years. Those who survived and remained on therapy derived long-term virologic and immunologic responses to ARV drugs in a manner similar to that observed in industrialized countries. Strategies to reduce the financial burden and other barriers to uninterrupted care as well as incentives to increase such practice models should be further explored in the African context.