The Clinical Impact of Continuing to Prescribe Antiretroviral Therapy in Patients with Advanced AIDS Who Manifest No Virologic or Immunologic Benefit

Introduction: Despite the efficacy and tolerability of modern antiretroviral therapy (ART), many patients with advanced AIDS prescribed these regimens do not achieve viral suppression or immune reconstitution as a result of poor adherence, drug resistance, or both. The clinical outcomes of continued ART prescription for such patients have not been well characterized. Methods: We examined the causes and predictors of all-cause mortality, AIDS-defining conditions, and serious non-AIDS-defining events among a cohort of participants in a clinical trial of pre-emptive therapy for CMV disease. We focused on participants who, despite ART had failed to achieve virologic suppression and substantive immune reconstitution. Results: 233 ART-receiving participants entered with a median baseline CD4+ T cell count of 30/mm3 and plasma HIV RNA of 5 log10 copies/mL. During a median 96 weeks of follow-up, 24.0% died (a mortality rate of 10.7/100 patient-years); 27.5% reported a new AIDS-defining condition, and 22.3% a new serious non-AIDS event. Of the deaths, 42.8% were due to an AIDS-defining condition, 44.6% were due to a non-AIDS-defining condition, and 12.5% were of unknown etiology. Decreased risk of mortality was associated with baseline CD4+ T cell count ≥25/mm3 and lower baseline HIV RNA. Conclusions: Among patients with advanced AIDS prescribed modern ART who achieve neither virologic suppression nor immune reconstitution, crude mortality percentages appear to be lower than reported in cohorts of patients studied a decade earlier. Also, in contrast to the era before modern ART became available, nearly half of the deaths in our modern-era study were caused by serious non-AIDS-defining events. Even among the most advanced AIDS patients who were not obtaining apparent immunologic and virologic benefit from ART, continued prescription of these medications appears to alter the natural history of AIDS—improving survival and shifting the causes of death from AIDS- to non-AIDS-defining conditions

Socioeconomic inequalities in cervical precancer screening among women in Ethiopia, Malawi, Rwanda, Tanzania, Zambia and Zimbabwe: analysis of Population-Based HIV Impact Assessment surveys.

ObjectivesWe examined age, residence, education and wealth inequalities and their combinations on cervical precancer screening probabilities for women. We hypothesised that inequalities in screening favoured women who were older, lived in urban areas, were more educated and wealthier.DesignCross-sectional study using Population-Based HIV Impact Assessment data.SettingEthiopia, Malawi, Rwanda, Tanzania, Zambia and Zimbabwe. Differences in screening rates were analysed using multivariable logistic regressions, controlling for age, residence, education and wealth. Inequalities in screening probability were estimated using marginal effects models.ParticipantsWomen aged 25-49 years, reporting screening.Outcome measuresSelf-reported screening rates, and their inequalities in percentage points, with differences of 20%+ defined as high inequality, 5%-20% as medium, 0%-5% as low.ResultsThe sample size of participants ranged from 5882 in Ethiopia to 9186 in Tanzania. The screening rates were low in the surveyed countries, ranging from 3.5% (95% CI 3.1% to 4.0%) in Rwanda to 17.1% (95% CI 15.8% to 18.5%) and 17.4% (95% CI 16.1% to 18.8%) in Zambia and Zimbabwe. Inequalities in screening rates were low based on covariates. Combining the inequalities led to significant inequalities in screening probabilities between women living in rural areas aged 25-34 years, with a primary education level, from the lowest wealth quintile, and women living in urban areas aged 35-49 years, with the highest education level, from the highest wealth quintile, ranging from 4.4% in Rwanda to 44.6% in Zimbabwe.ConclusionsCervical precancer screening rates were inequitable and low. No country surveyed achieved one-third of the WHO's target of screening 70% of eligible women by 2030. Combining inequalities led to high inequalities, preventing women who were younger, lived in rural areas, were uneducated, and from the lowest wealth quintile from screening. Governments should include and monitor equity in their cervical precancer screening programmes

An Observational Cohort Comparison of Facilitators of Retention in Care and Adherence to Anti-Eetroviral Therapy at an HIV Treatment Center in Kenya

BACKGROUND: Most HIV treatment programs in resource-limited settings utilize multiple facilitators of adherence and retention in care but there is little data on the efficacy of these methods. We performed an observational cohort analysis of a treatment program in Kenya to assess which program components promote adherence and retention in HIV care in East Africa. METHODS: Patients initiating ART at A.I.C. Kijabe Hospital were prospectively enrolled in an observational study. Kijabe has an intensive program to promote adherence and retention in care during the first 6 months of ART that incorporates the following facilitators: home visits by community health workers, community based support groups, pharmacy counseling, and unannounced pill counts by clinicians. The primary endpoint was time to treatment failure, defined as a detectable HIV-1 viral load; discontinuation of ART; death; or loss to follow-up. Time to treatment failure for each facilitator was calculated using Kaplan-Meier analysis. The relative effects of the facilitators were determined by the Cox Proportional Hazards Model. RESULTS: 301 patients were enrolled. Time to treatment failure was longer in patients participating in support groups (448 days vs. 337 days, P<0.001), pharmacy counseling (480 days vs. 386 days, P = 0.002), pill counts (482 days vs. 189 days, P<0.001) and home visits (485 days vs. 426 days, P = 0.024). Better adherence was seen with support groups (89% vs. 82%, P = 0.05) and pill counts (89% vs. 75%, P = 0.02). Multivariate analysis using the Cox Model found significant reductions in risk of treatment failure associated with pill counts (HR = 0.19, P<0.001) and support groups (HR = 0.43, P = 0.003). CONCLUSION: Unannounced pill counts by the clinician and community based support groups were associated with better long term treatment success and with better adherence

Meningococcal Factor H Binding Proteins in Epidemic Strains from Africa: Implications for Vaccine Development

Epidemics of meningococcal meningitis are common in sub-Saharan Africa. Most are caused by encapsulated serogroup A strains, which rarely cause disease in industrialized countries. A serogroup A polysaccharide protein conjugate vaccine recently was introduced in some countries in sub-Saharan Africa. The antibodies induced, however, may allow replacement of serogroup A strains with serogroup W-135 or X strains, which also cause epidemics in this region. Protein antigens, such as factor H binding protein (fHbp), are promising for prevention of meningococcal serogroup B disease. These proteins also are present in strains with other capsular serogroups. Here we report investigation of the potential of fHbp vaccines for prevention of disease caused by serogroup A, W-135 and X strains from Africa. Four fHbp amino acid sequence variants accounted for 81% of the 106 African isolates studied. While there was little cross-protective activity by antibodies elicited in mice by recombinant fHbp vaccines from each of the four sequence variants, a prototype native outer membrane vesicle (NOMV) vaccine from a mutant with over-expressed fHbp elicited antibodies with broad protective activity. A NOMV vaccine has the potential to supplement coverage by the group A conjugate vaccine and help prevent emergence of disease caused by non-serogroup A strains

The use of pill counts as a facilitator of adherence with antiretroviral therapy in resource limited settings.

Pill counts are often used to measure adherence to ART, but there is little data on how they affect adherence. We previously showed a bivariate relationship between clinicians counting pills and adherence in patients receiving HIV care in Kenya. We present a secondary analysis of the relationship between numbers of pill counts and clinical outcomes in resource limited settings.Patients initiating ART at Kijabe Hospital were monitored for the number of discretionary pill counts performed by their clinician in the first 6 months of ART. Subjects were followed for at least 1 year after enrollment. The number of clinician pill counts was correlated to ART adherence. The primary endpoints were time to treatment failure, defined as a detectable HIV-1 viral load, death; or loss to follow-up.Clinician pill counts were done at 68% of clinic visits for 304 subjects. There was a positive correlation between the number of clinician pill counts and ART adherence (r = 0.21, p <0.001). Patients were divided into 3 groups (0 counts, 1 to 3 counts, 4 to 7 counts) and exhibited adherence of 76%, 84%, and 92%, respectively (p = 0.004). Time to treatment failure for these groups was 220 days, 438 days, and 497 days (P<0.01), respectively. Time to virologic failure in living patients remaining in the cohort was longer in those with more pill count (P =0.02). Multi-variate analysis adjusting for co-variates affecting time to treatment failure found that that clinician pill counts were associated with a decreased risk of treatment failure (HR = 0.69, p =0.04).The number of clinician pill count performed was independently associated with better adherence and a decreased risk of treatment failure. The use of clinician pill counts should be further studied as an adherence promoter through a randomized clinical trial

Time to Treatment Failure Categorized by Interventions.

<p>Kaplan Meier plots of time to treatment failure stratified by: A) participation in two or more support group meetings; B) having four or more unannounced pill counts by primary care provider; C) at least one home visit; D) having two or more counseling sessions by a pharmacist.</p

Schematic Diagram of HIV Program and Observational Study Design.

<p>The HIV program is divided into 3 distinct activities, HIV testing, Treatment Preparation, and Antiretroviral treatment that includes both community and clinic based facilitators. For entry into the study, subjects must be HIV positive and complete all treatment preparation activities. The study period begins with initiation of ART and evaluates the effects of treatment facilitators on treatment success.</p