Viability and effectiveness of large-scale HIV treatment initiatives in sub-Saharan Africa: experience from western Kenya

Division of Infectious Diseases, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States
AIDS (Impact Factor: 6.56). 01/2006; 20(1):41-8. DOI: 10.1097/01.aids.0000196177.65551.ea
Source: PubMed

ABSTRACT To determine the clinical and immunological outcomes of a cohort of HIV-infected patients receiving antiretroviral therapy.
Retrospective study of prospectively collected data from consecutively enrolled adult HIV-infected patients in eight HIV clinics in western Kenya.
CD4 cell counts, weight, mortality, loss to follow-up and adherence to antiretroviral therapy were collected for the 2059 HIV-positive non-pregnant adult patients treated with antiretroviral drugs between November 2001 and February 2005.
Median duration of follow-up after initiation of antiretroviral therapy was 40 weeks (95% confidence interval, 38-43); 111 patients (5.4%) were documented as deceased and 505 (24.5%) were lost to follow-up. Among 1766 (86%) evaluated for adherence to their antiretroviral regimen, 78% reported perfect adherence at every visit. Although patients with and without perfect adherence gained weight, patients with less than perfect adherence gained 1.04 kg less weight than those reporting perfect adherence (P = 0.059). CD4 cell counts increased by a mean of 109 cells/microl during the first 6 weeks of therapy and increased more slowly thereafter, resulting in overall CD4 cell count increases of 160, 225 and 297 cells/microl at 12, 24, and 36 months respectively. At 1 year, a mean increase of 170 cells/microl was seen among patients reporting perfect adherence compared with 123 cells/microl among those reporting some missed doses (P < 0.001).
Antiretroviral treatment of adult Kenyans in this cohort resulted in significant and persistent clinical and immunological benefit. These findings document the viability and effectiveness of large-scale HIV treatment initiatives in resource-limited settings.

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    Journal of AIDS & Clinical Research 01/2014; 5(10). · 6.83 Impact Factor
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    ABSTRACT: Antiretroviral resistance leads to treatment failure and resistance transmission. Resistance data in western Kenya are limited. Collection of non-plasma analytes may provide additional resistance information. We assessed HIV diversity using the REGA tool, transmitted resistance by the WHO mutation list and acquired resistance upon first-line failure by the IAS-USA mutation list, at the Academic Model Providing Access to Healthcare (AMPATH), a major treatment programme in western Kenya. Plasma and four non-plasma analytes, dried blood-spots (DBS), dried plasma-spots (DPS), ViveSTTM-plasma (STP) and ViveST-blood (STB), were compared to identify diversity and evaluate sequence concordance. Among 122 patients, 62 were treatment-naïve and 60 treatment-experienced; 61% were female, median age 35 years, median CD4 182 cells/µL, median viral-load 4.6 log10 copies/mL. One hundred and ninety-six sequences were available for 107/122 (88%) patients, 58/62 (94%) treatment-naïve and 49/60 (82%) treated; 100/122 (82%) plasma, 37/78 (47%) attempted DBS, 16/45 (36%) attempted DPS, 14/44 (32%) attempted STP from fresh plasma and 23/34 (68%) from frozen plasma, and 5/42 (12%) attempted STB. Plasma and DBS genotyping success increased at higher VL and shorter shipment-to-genotyping time. Main subtypes were A (62%), D (15%) and C (6%). Transmitted resistance was found in 1.8% of plasma sequences, and 7% combining analytes. Plasma resistance mutations were identified in 91% of treated patients, 76% NRTI, 91% NNRTI; 76% dual-class; 60% with intermediate-high predicted resistance to future treatment options; with novel mutation co-occurrence patterns. Nearly 88% of plasma mutations were identified in DBS, 89% in DPS and 94% in STP. Of 23 discordant mutations, 92% in plasma and 60% in non-plasma analytes were mixtures. Mean whole-sequence discordance from frozen plasma reference was 1.1% for plasma-DBS, 1.2% plasma-DPS, 2.0% plasma-STP and 2.3% plasma-STB. Of 23 plasma-STP discordances, one mutation was identified in plasma and 22 in STP (p<0.05). Discordance was inversely significantly related to VL for DBS. In a large treatment programme in western Kenya, we report high HIV-1 subtype diversity; low plasma transmitted resistance, increasing when multiple analytes were combined; and high-acquired resistance with unique mutation patterns. Resistance surveillance may be augmented by using non-plasma analytes for lower-cost genotyping in resource-limited settings.
    Journal of the International AIDS Society 11/2014; 17(1):19262. DOI:10.7448/IAS.17.1.19262 · 4.21 Impact Factor
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    ABSTRACT: Background: The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We conducted a cluster randomized trial to compare the use of routine VL testing versus our local standard of care (based on immunological and clinical treatment failure criteria and limited VL testing) to improve long-term clinical outcomes. Methods: ART-naïve patients initiating therapy were enrolled at six intervention and six control ART clinics in Lusaka, Zambia. Sites were matched by historical mortality rate, size, and other characteristics. VL measurements were performed at ART-initiation and at 3, 6, 12, and 18 months in the intervention arm. The study was powered to detect a 36% reduction in mortality at 18 months. Results: From December 2006 to May 2008, we completed enrollment of 1973 participants. Overall, mean age was 34.6 years, 60% were female, and 65% had WHO stage 3 or 4 disease. Mean CD4+ lymphocyte count was 146 cells/mm3. Measured baseline characteristics did not differ significantly between the study arms. Early discontinuations exceeded estimates; 11% of participants were deceased, delinquent (defined as >37 days late to pharmacy) or had withdrawn at 180 days in both study arms (p=0.16). Conclusion: We now estimate that at least 36 months of follow-up is required to detect differences in the primary endpoint. The successful implementation of a large clinical trial of HIV-1 VL monitoring in sub-Saharan Africa is feasible but requires long-term follow-up and, therefore, extensive support. Such cohorts will likely prove valuable in determining long-term outcomes in resource-constrained settings.
    Infectious Diseases Society of America 2009 Annual Meeting; 10/2009

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