Kericho CLinic-based ART Diagnostic Evaluation (CLADE): design, accrual, and baseline characteristics of a randomized controlled trial conducted in predominately rural, district-level, HIV clinics of Kenya.

BACKGROUND: Prospective clinical trial data regarding routine HIV-1 viral load (VL) monitoring of antiretroviral therapy (ART) in non-research clinics of Sub-Saharan Africa are needed for policy makers. METHODS: CLinic-based ART Diagnostic Evaluation (CLADE) is a randomized, controlled trial (RCT) evaluating feasibility, superiority, and cost-effectiveness of routine VL vs. standard of care (clinical and immunological) monitoring in adults initiating dual nucleoside reverse transcriptase inhibitor (NRTI)+non-NRTI ART. Participants were randomized (1:1) at 7 predominately rural, non-research, district-level clinics of western Kenya. Descriptive statistics present accrual patterns and baseline cohort characteristics. RESULTS: Over 15 months, 820 adults enrolled at 7 sites with 86-152 enrolled per site. Monthly site enrollment ranged from 2-92 participants. Full (100%) informed consent compliance was independently documented. Half (49.9%) had HIV diagnosed through voluntary counseling and testing. Study arms were similar: mostly females (57.6%) aged 37.6 (SD = 9.0) years with low CD4 (166 [SD = 106]) cells/m3). Notable proportions had WHO Stage III or IV disease (28.7%), BMI <18.5 kg/m2 (23.1%), and a history of tuberculosis (5.6%) or were receiving tuberculosis treatment (8.2%) at ART initiation. In the routine VL arm, 407/409 (99.5%) received baseline VL (234,577 SD = 151,055 copies/ml). All participants received lamivudine; 49.8% started zidovudine followed by 38.4% stavudine and 11.8% tenofovir; and, 64.4% received nevirapine as nNRTI (35.6% efavirenz). CONCLUSIONS: A RCT can be enrolled successfully in rural, non-research, resource limited, district-level clinics in western Kenya. Many adults presenting for ART have advanced HIV/AIDS, emphasizing the importance of universal HIV testing and linkage-to-care campaigns. TRIAL REGISTRATION: ClinicalTrials.gov NCT01791556.

Using standard and institutional mentorship models to implement SLMTA in Kenya.

BACKGROUND: Kenya is home to several high-performing internationally-accredited research laboratories, whilst most public sector laboratories have historically lacked functioning quality management systems. In 2010, Kenya enrolled an initial eight regional and four national laboratories into the Strengthening Laboratory Management Toward Accreditation (SLMTA) programme. To address the challenge of a lack of mentors for the regional laboratories, three were paired, or 'twinned', with nearby accredited research laboratories to provide institutional mentorship, whilst the other five received standard mentorship. OBJECTIVES: This study examines results from the eight regional laboratories in the initial SLMTA group, with a focus on mentorship models. METHODS: Three SLMTA workshops were interspersed with three-month periods of improvement project implementation and mentorship. Progress was evaluated at baseline, mid-term, and exit using the Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) audit checklist and scores were converted into a zero- to five-star scale. RESULTS: At baseline, the mean score for the eight laboratories was 32%; all laboratories were below the one-star level. At mid-term, all laboratories had measured improvements. However, the three twinned laboratories had increased an average of 32 percentage points and reached one to three stars; whilst the five non-twinned laboratories increased an average of 10 percentage points and remained at zero stars. At exit, twinned laboratories had increased an average 12 additional percentage points (44 total), reaching two to four stars; non-twinned laboratories increased an average of 28 additional percentage points (38 total), reaching one to three stars. CONCLUSION: The partnership used by the twinning model holds promise for future collaborations between ministries of health and state-of-the-art research laboratories in their regions for laboratory quality improvement. Where they exist, such laboratories may be valuable resources to be used judiciously so as to accelerate sustainable quality improvement initiated through SLMTA.

Occurrence of etravirine/rilpivirine-specific resistance mutations selected by efavirenz and nevirapine in Kenyan patients with non-B HIV-1 subtypes failing antiretroviral therapy.

Resistance to efavirenz and nevirapine has not been associated with mutations at position 138 of reverse transcriptase. In an evaluation of virologic suppression rates in PEPFAR (President's Emergency Plan For AIDS Relief) clinics in Kenya among patients on first-line therapy (RV288), 63% (617/975) of randomly selected patients on antiretroviral therapy were suppressed (HIV RNA<400 copies/ml). Among those with non-nucleoside reverse transcriptase inhibitor resistance (n = 101), 14 (13.8%) had substitutions at 138 (A, G, K or Q), mutations selected only by etravirine and rilpivirine in subtype B viruses. All 14 patients received efavirenz or nevirapine, not etravirine or rilpivirine, and were predominantly subtype A1. This may be the first report of efavirenz and nevirapine selecting these mutations in these subtypes.