Abraham Siika

Assessment of second-line antiretroviral regimens for HIV therapy in Africa

BACKGROUND The efficacy and toxic effects of nucleoside reverse-transcriptase inhibitors (NRTIs) are uncertain when these agents are used with a protease inhibitor in second-line therapy for human immunodeficiency virus (HIV) infection in resource-limited settings. Removing the NRTIs or replacing them with raltegravir may provide a benefit. METHODS In this open-label trial in sub-Saharan Africa, we randomly assigned 1277 adults and adolescents with HIV infection and first-line treatment failure to receive a ritonavir-boosted protease inhibitor (lopinavir-ritonavir) plus clinician-selected NRTIs (NRTI group, 426 patients), a protease inhibitor plus raltegravir in a superiority comparison (raltegravir group, 433 patients), or protease-inhibitor monotherapy after 12 weeks of induction therapy with raltegravir in a noninferiority comparison (monotherapy group, 418 patients). The primary composite end point, good HIV disease control, was defined as survival with no new World Health Organization stage 4 events, a CD4+ count of more than 250 cells per cubic millimeter, and a viral load of less than 10,000 copies per milliliter or 10,000 copies or more with no protease resistance mutations at week 96 and was analyzed with the use of imputation of data (≤4%). RESULTS Good HIV disease control was achieved in 60% of the patients (mean, 255 patients) in the NRTI group, 64% of the patients (mean, 277) in the raltegravir group (P=0.21 for the comparison with the NRTI group; superiority of raltegravir not shown), and 55% of the patients (mean, 232) in the monotherapy group (noninferiority of monotherapy not shown, based on a 10-percentage-point margin). There was no significant difference in rates of grade 3 or 4 adverse events among the three groups (P=0.82). The viral load was less than 400 copies per milliliter in 86% of patients in the NRTI group, 86% in the raltegravir group (P=0.97), and 61% in the monotherapy group (P<0.001). CONCLUSIONS When given with a protease inhibitor in second-line therapy, NRTIs retained substantial virologic activity without evidence of increased toxicity, and there was no advantage to replacing them with raltegravir. Virologic control was inferior with protease-inhibitor monotherapy. (Funded by European and Developing Countries Clinical Trials Partnership and others; EARNEST Current Controlled Trials number, ISRCTN37737787, and ClinicalTrials.gov number, NCT00988039.).

Antiretroviral Therapies in Women after Single-Dose Nevirapine Exposure

BACKGROUND Peripartum administration of single-dose nevirapine reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but selects for nevirapine-resistant virus. METHODS In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single-dose nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir–emtricitabine plus nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary end point was the time to confirmed virologic failure or death. RESULTS A total of 241 women who had been exposed to single-dose nevirapine began the study treatments (121 received nevirapine and 120 received ritonavir-boosted lopinavir). Significantly more women in the nevirapine group reached the primary end point than in the ritonavir-boosted lopinavir group (26% vs. 8%) (adjusted P=0.001). Virologic failure occurred in 37 (28 in the nevirapine group and 9 in the ritonavir-boosted lopinavir group), and 5 died without prior virologic failure (4 in the nevirapine group and 1 in the ritonavir-boosted lopinavir group). The group differences appeared to decrease as the interval between single-dose nevirapine exposure and the start of antiretroviral therapy increased. Retrospective bulk sequencing of baseline plasma samples showed nevirapine resistance in 33 of 239 women tested (14%). Among 500 women without prior exposure to single-dose nevirapine, 34 of 249 in the nevirapine group (14%) and 36 of 251 in the ritonavir-boosted lopinavir group (14%) had virologic failure or died. CONCLUSIONS In women with prior exposure to peripartum single-dose nevirapine (but not in those without prior exposure), ritonavir-boosted lopinavir plus tenofovir–emtricitabine was superior to nevirapine plus tenofovir–emtricitabine for initial antiretroviral therapy. (Funded by the National Institute of Allergy and Infectious Diseases and the National Research Center; ClinicalTrials.gov number, NCT00089505.).

An electronic medical record system for ambulatory care of HIV-infected patients in Kenya

Administering and monitoring therapy is crucial to the battle against HIV/AIDS in sub-Saharan Africa. Electronic medical records (EMRs) can aid in documenting care, monitoring drug adherence and response to therapy, and providing data for quality improvement and research. Faculty at Moi University in Kenya and Indiana and University in the USA opened adult and pediatric HIV clinics in a national referral hospital, a district hospital, and six rural health centers in western Kenya using a newly developed EMR to support comprehensive outpatient HIV/AIDS care. Demographic, clinical, and HIV risk data, diagnostic test results, and treatment information are recorded on paper encounter forms and hand-entered into a central database that prints summary flowsheets and reminders for appropriate testing and treatment. There are separate modules for monitoring the Antenatal Clinic and Pharmacy. The EMR was designed with input from clinicians who understand the local community and constraints of providing care in resource poor settings. To date, the EMR contains more than 30,000 visit records for more than 4000 patients, almost half taking antiretroviral drugs. We describe the development and structure of this EMR and plans for future development that include wireless connections, tablet computers, and migration to a Web-based platform.

Impact of integrated family planning and HIV care services on contraceptive use and pregnancy outcomes: a retrospective cohort study.

ObjectiveTo determine the impact of routine care (RC) and integrated family planning (IFP) and HIV care service on family planning (FP) uptake and pregnancy outcomes. DesignRetrospective cohort study conducted between October 10, 2005, and February 28, 2009. SettingUnited States Agency for International Development—Academic Model Providing Access To Healthcare (USAID-AMPATH) in western Kenya. SubjectsRecords of adult HIV-infected women. InterventionIntegration of FP into one of the care teams. Primary Outcomes MeasuresIncidence of FP methods and pregnancy. ResultsFour thousand thirty-one women (1453 IFP; 2578 RC) were eligible. Among the IFP group, there was a 16.7% increase (P < 0.001) [95% confidence interval (CI): 13.2% to 20.2%] in incidence of condom use, 12.9% increase (P < 0.001) (95% CI: 9.4% to 16.4%) in incidence of FP use including condoms, 3.8% reduction (P < 0.001) (95% CI: 1.9% to 5.6%) in incidence of FP use excluding condoms, and 0.1% increase (P = 0.9) (95% CI: −1.9% to 2.1%) in incidence of pregnancies. The attributable risk of the incidence rate per 100 person-years of IFP and RC for new condom use was 16.4 (95% CI: 11.9 to 21.0), new FP use including condoms was 13.5 (95% CI: 8.7 to 18.3), new FP use excluding condoms was −3.0 (95% CI: −4.6 to −1.4) and new cases of pregnancies was 1.2 (95% CI: −0.6 to 3.0). ConclusionsIntegrating FP services into HIV care significantly increased the use of modern FP methods but no impact on pregnancy incidence. HIV programs need to consider integrating FP into their program structure.

Experience implementing electronic health records in three East African countries.

INTRODUCTION Efficient use of health care resources in low-income countries by providers and local and national managers requires timely access to patient data. OBJECTIVE To implement electronic health records (EHRs) in HIV clinics in Kenya, Tanzania, and Uganda. RESULTS We initially developed and implemented an EHR in Kenya through a mature academic partnership. The EHR was then implemented in six HIV clinics in Tanzania and Uganda in collaboration with their National AIDS Control Programmes. All implementations were successful, but the systems use and sustainability varied depending on who controlled clinic funding. CONCLUSIONS Successful EHR use and sustainability were enhanced by local control of funds, academic partnerships (mainly by leveraging research funds), and in-country technology support.

Differences between self-reported and electronically monitored adherence among patients receiving antiretroviral therapy in a resource-limited setting.

Background:Measurement of adherence to antiretroviral therapy (ART) by patient self-report is common in resource-limited settings but widely believed to overstate actual adherence. The extent to which these measures overstate adherence has not been examined among a large patient population. Methods:HIV-infected adult patients in Kenya who initiated ART within the past 3 months were followed for 6 months. Adherence was measured by participants’ self-reports of doses missed in the past 7 days during monthly clinic visits and by continuous Medication Event Monitoring System (MEMS) in participants’ pill bottles. Seven-day self-reported adherence was compared to 7-day MEMS adherence, 30-day MEMS adherence, and adherence more than 90% during each of the first 6 months. Results:Self-reported and MEMS adherence measures were linked for 669 participants. Mean 7-day self-reported adherence was 98.7% and mean 7-day MEMS adherence was 86.0%, a difference of 12.7% (P < 0.01). The difference between the two adherence measures increased over time due to a decline in 7-day MEMS adherence. However, patients with lower MEMS adherence were in fact more likely to self-report missed doses and the difference between self-reported and MEMS adherence was similar for each number of self-reported missed doses. When analysis was limited to patients who reported rarely or never removing multiple doses at the same time, mean difference was 10.5% (P < 0.01). Conclusion:There is a sizable and significant difference between self-reported and MEMS adherence. However, a strong relationship between the measures suggests that self-reported adherence is informative for clinical monitoring and program evaluation.

A clinician-nurse model to reduce early mortality and increase clinic retention among high-risk HIV-infected patients initiating combination antiretroviral treatment

BackgroundIn resource-poor settings, mortality is at its highest during the first 3 months after combination antiretroviral treatment (cART) initiation. A clear predictor of mortality during this period is having a low CD4 count at the time of treatment initiation. The objective of this study was to evaluate the effect on survival and clinic retention of a nurse-based rapid assessment clinic for high-risk individuals initiating cART in a resource-constrained setting.MethodsThe USAID-AMPATH Partnership has enrolled more than 140,000 patients at 25 clinics throughout western Kenya. High Risk Express Care (HREC) provides weekly or bi-weekly rapid contacts with nurses for individuals initiating cART with CD4 counts of ≤100 cells/mm3. All HIV-infected individuals aged 14 years or older initiating cART with CD4 counts of ≤100 cells/mm3 were eligible for enrolment into HREC and for analysis. Adjusted hazard ratios (AHRs) control for potential confounding using propensity score methods.ResultsBetween March 2007 and March 2009, 4,958 patients initiated cART with CD4 counts of ≤100 cells/mm3. After adjusting for age, sex, CD4 count, use of cotrimoxazole, treatment for tuberculosis, travel time to clinic and type of clinic, individuals in HREC had reduced mortality (AHR: 0.59; 95% confidence interval: 0.45-0.77), and reduced loss to follow up (AHR: 0.62; 95% CI: 0.55-0.70) compared with individuals in routine care. Overall, patients in HREC were much more likely to be alive and in care after a median of nearly 11 months of follow up (AHR: 0.62; 95% CI: 0.57-0.67).ConclusionsFrequent monitoring by dedicated nurses in the early months of cART can significantly reduce mortality and loss to follow up among high-risk patients initiating treatment in resource-constrained settings.

The structure and outcomes of a HIV postexposure prophylaxis program in a high HIV prevalence setup in western Kenya.

Background:In 2001, HIV postexposure prophylaxis (PEP) was initiated in western Kenya. Methods:Design, implementation, and evolution of the PEP program are described. Patient data were analyzed for reasons, time to initiation, and PEP outcome. Results:Occupational PEP was initiated first followed by nonoccupational PEP (nPEP). Antiretroviral regimens were based upon national PEP guidelines, affordability and availability, and prevailing HIV prevalence. Emerging side effects data and cost improvements influenced regimen changes. Between November 2001 and December 2006, 446 patients sought PEP. Occupational exposure: 91 patients: 51 males; 72 accepted HIV testing; 48 of 52 source patients were HIV infected; median exposure-PEP time 3 hours (range: 0.3-96 hours). Of 72 HIV-negative patients receiving PEP, 3 discontinued, 69 completed, and 23 performed post-PEP HIV RNA polymerase chain reaction (all negative). Eleven follow-up HIV enzyme-linked immunosorbent assay tests have all turned negative. Nonoccupational exposure: 355 patients; 285 females; 90 children; 300 accepted HIV testing; median exposure-nPEP time 19 hours (range: 1-672 hours). Of 296 HIV-negative patients on nPEP, 1 died, 15 discontinued, 104 are on record having completed PEP, and 129 returned for 6-week HIV RNA polymerase chain reaction (1 patient tested positive). Eighty-seven follow-up HIV enzyme-linked immunosorbent assay tests have all turned negative. Conclusions:It is feasible to provide PEP and nPEP in resource-constrained settings.

The impact of the President's Emergency Plan for AIDS Relief on expansion of HIV care services for adult patients in western Kenya.

Background:The Presidents Emergency Plan for AIDS Relief committed

Enhanced Prophylaxis plus Antiretroviral Therapy for Advanced HIV Infection in Africa

15 billion to addressing HIV in resource-poor settings. Objective:To assess the impact of The Presidents Emergency Plan for AIDS Relief on the treatment services of an HIV care program. Design, setting, and patients:Cohort study utilizing computerized medical records of nonpregnant adults enrolled into the Academic Model for the Prevention and Treatment of HIV/AIDS system, in western Kenya between 27 November 2001 and 24 July 2006. Main outcomes measures:Number of clinics and patients enrolled in Academic Model for the Prevention and Treatment of HIV/AIDS, as well as patient demographics, immunologic, and clinical characteristics during three periods defined by the availability of combination antiretroviral therapy (cART). Results:Enrollment as of May 2006 was 23 539. Mean monthly enrollment increased from 64 to 815 between periods 1 and 3. The median CD4 cell count at enrollment during period 3 (172 cells/μl) was significantly higher than for period 2 (119 cells/μl; P < 0.001). World Health Organization stage at enrollment differed significantly between periods with 6.7% having stage 4 disease in period 3 compared with 13.8% during period 1 (P < 0.001). Significantly more patients had complete documentation of cART eligibility, during period 3 as compared with the previous periods. Time from enrollment to cART initiation decreased from a median of 64 weeks in period 1 to 12 weeks during period 3 (P < 0.001). Conclusion:The Presidents Emergency Plan for AIDS Relief funding has allowed Academic Model for the Prevention and Treatment of HIV/AIDS to significantly increase the number of individuals receiving HIV care and provided the ability to expand services allowing for identification of patients earlier in their disease process.