Frank Kaharuza

Disclosure of HIV Status and Adherence to Daily Drug Regimens Among HIV-infected Children in Uganda

Pediatric adherence to daily drug regimens has not been widely assessed in Africa where majority of HIV infected children live. Using in-depth interviews of 42 HIV-infected children taking ART and/or cotrimoxazole prophylaxis, and 42 primary caregivers, at a comprehensive HIV/AIDS clinic in Uganda, we evaluated their adherence experiences for purposes of program improvement. Daily drug regimens provided by the pediatric clinic included cotrimoxazole prophylaxis as well as ART and cotrimoxazole combined. Complete disclosure of HIV status by caregivers to children and strong parental relationships were related to good adherence. Structural factors including poverty and stigma were barriers to adherence even for children who had had complete disclosure and a supportive relationship with a parent. To ensure adherence to life-extending medications, our findings underscore the need for providers to support caregivers to disclose, provide on-going support and maintain open communication with HIV-infected children taking cotrimoxazole prophylaxis and ART.

Population-Based Hematologic and Immunologic Reference Values for a Healthy Ugandan Population

ABSTRACT To assess the validity of the reference values for hematologic and immunologic indices currently used in Africa, we evaluated blood samples from 3,311 human immunodeficiency virus (HIV)-negative Ugandans aged 1 week to 92 years. Erythrocyte, hemoglobin, and hematocrit levels and mean corpuscular volume all significantly increased with age (P < 0.001) and were independent of gender until the age of 13 years, after which the levels were higher in males than in females (P < 0.001). White blood cell, neutrophil, lymphocyte, basophil, and monocyte counts significantly declined with age until the age of 13 years (P < 0.001), with no differences by gender, while platelet counts declined with age (P < 0.001) and showed differences by gender only among adults older than age 24 years. CD4+- and CD8+-cell counts declined with age until the age of 18 years; thereafter, females had higher counts than males. The absolute values for many of these parameters differed from those reported for populations outside Africa, suggesting that it may be necessary to develop tables of reference values for hematologic and immunologic indices specific for the African population. This may be particularly important with regard to CD4+-cell counts among children because significant differences in absolute and percent CD4+-cell counts exist between the values for Western populations and the values for the population evaluated in our study. These differences could influence the decision to initiate antiretroviral therapy among children infected with HIV.

Risk Factors for Recent HIV Infection in Uganda

CONTEXT Studies of factors associated with acquiring human immunodeficiency virus (HIV) are often based on prevalence data that might not reflect recent infections. OBJECTIVE To determine demographic, biological, and behavioral factors for recent HIV infection in Uganda. DESIGN AND SETTING Nationally representative household survey of cross-sectional design conducted in Uganda from August 2004 through January 2005; data were analyzed until November 2007. PARTICIPANTS There were 11,454 women and 9905 men aged 15 to 59 years who were eligible. Questionnaires were completed for 10,826 women (95%) and 8830 men (89%); of those interviewed, blood specimens were collected for 10,227 women (94%) and 8298 men (94%). MAIN OUTCOME MEASURE Specimens seropositive for HIV were tested with the BED IgG capture-based enzyme immunosorbent assay to identify recent seroconversions (median, 155 days) using normalized optical density of 0.8 and adjustments. RESULTS Of the 1023 HIV infections with BED results, 172 (17%) tested as recent. In multivariate analysis, risk factors associated with recent HIV infection included female sex (adjusted odds ratio [aOR], 2.4; 95% confidence interval [CI], 1.1-5.2); current marital status (widowed vs never married, aOR, 6.1; 95% CI, 2.8-13.3; divorced vs never married, aOR, 3.0; 95% CI, 1.5-6.1); geographic region (north central Uganda vs central Uganda/Kampala, aOR, 2.6; 95% CI, 1.7-4.1); number of sex partners in past year (> or = 2 compared with none; aOR, 2.9; 95% CI, 1.6-5.5); herpes simplex virus type 2 infection (aOR, 3.9; 95% CI, 2.6-5.8); report of a sexually transmitted disease in the past year (aOR, 1.7; 95% CI, 1.2-2.4); and being an uncircumcised man (aOR, 2.5; 95% CI, 1.1-5.3). Among married participants, recent HIV infection was associated with never using condoms with partners outside of marriage (aOR, 3.2; 95% CI, 1.7-6.1) compared with individuals having no outside partners. The risk of incident HIV infection for married individuals who used condoms with at least 1 outside partner was similar to that of those who did not have any partners outside of marriage (aOR, 1.0; 95% CI, 0.3-2.7). CONCLUSION A survey of individuals in Uganda who were tested with an HIV assay used to establish recent infection identified risk factors, which offers opportunities for prevention initiatives.

The dilemma of safe sex and having children: challenges facing HIV sero-discordant couples in Uganda

CONTEXT Contraceptive discontinuation is a common event that may be associated with low motivation to avoid pregnancy. If this is the case, a substantial proportion of pregnancies that follow discontinuation will be reported as intended. METHODS Demographic and Health Survey data from six countries (Bangladesh, the Dominican Republic, Kazakhstan, Kenya, the Philippines and Zimbabwe) over the period 1999-2003 were used to explore the proportions of pregnancies women reported as intended or unintended following various contraceptive behaviors. Multivariate logistic regression analysis was used to examine the characteristics of women who reported births as intended when they followed contraceptive failure or discontinuation for reasons other than a desire for pregnancy. RESULTS The proportion of births reported as intended following contraceptive failure ranged from 16% in Bangladesh to 54% in Kazakhstan, and the proportion reported as intended following discontinuation for reasons other than a desire for pregnancy ranged from 37% in Kenya to 51% in Kazakhstan. In at least half the countries, associations were found between selected womens characteristics and their reports that births following either contraceptive failure or discontinuation were intended: Factors that were positively associated were womens age and the time elapsed between contraceptive discontinuation and the index conception; factors that were negatively associated were increasing number of living children and reporting method failure as opposed to method discontinuation. CONCLUSION These findings suggest that underlying variation in the motivation to avoid pregnancy is an important factor in contraceptive discontinuation.BACKGROUND Sixty percent of new HIV infections in Uganda occur in stable relationships between HIV discordant couples. Given the importance of fertility in Uganda, we hypothesized that unsafe sexual practices may be used to found a family/replace a dead child. Thus, we explored sexual practices to understand to what extent these are influenced by the desire to have children and the implications for HIV transmission among discordant couples. METHODS A cross-sectional survey of 114 HIV discordant couples in Kampala, and in-depth interviews with 15 purposively selected couples. Quantitative data were analysed using STATA. Multivariate logistic regression analysis done to identify factors associated with consistent condom use. Thematic content analysis of qualitative data was done using NVIVO 2. RESULTS Participants wanting children and those with multiple sexual partners were less likely to use condoms (Adj OR 0.51, and 0.36 respectively). Three of the five types of sexual practices used by couples do not allow pregnancy to occur. Main reasons for wanting a child included: ensuring lineage continuity and posterity, securing relationships and pressure from relatives to reproduce. Challenges included: risk of HIV transmission to partner and child, lack of negotiating power for safer sex, failure of health systems to offer safe methods of reproduction CONCLUSIONS HIV sero-discordant couples with strong desire for childbearing have a dilemma of risking HIV infection or infecting their spouse. Some risk transmission of HIV infection to reproduce. We need to address gender issues, risky behaviour and reproductive health services for HIV sero-discordant couples.

Utility of routine viral load, CD4 cell count, and clinical monitoring among adults with HIV receiving antiretroviral therapy in Uganda: randomised trial

Objective To evaluate the use of routine laboratory monitoring in terms of clinical outcomes among patients receiving antiretroviral therapy (ART) in Uganda. Design Randomised clinical trial Setting A home based ART programme in rural Uganda. Participants All participants were people with HIV who were members of the AIDS Support Organisation. Participants had CD4 cell counts <250 cells × 106/L or World Health Organization stage 3 or 4 disease. Interventions Participants were randomised to one of three different monitoring arms: a viral load arm (clinical monitoring, quarterly CD4 counts, and viral load measurements), CD4 arm (clinical monitoring and CD4 counts), or clinical arm (clinical monitoring alone). Main outcome measures Serious morbidity (newly diagnosed AIDS defining illness) and mortality. Results 1094 participants started ART; median CD4 count at baseline was 129 cells × 106/L. Median follow-up was three years. In total, 126 participants died (12%), 148 (14%) experienced new AIDS defining illnesses, and 61(6%) experienced virological failure, defined as two consecutive viral loads >500 copies/mL occurring more than three months after the start of ART. After adjustment for age, sex, baseline CD4 count, viral load, and body mass index, the rate of new AIDS defining events or death was higher in the clinical arm than the viral load arm (adjusted hazard ratio 1.83, P=0.002) or the CD4 arm (1.49, P=0.032). There was no significant difference between the CD4 arm and the viral load arm (1.23, P=0.31). Conclusion In patients receiving ART for HIV infection in Uganda, routine laboratory monitoring is associated with improved health and survival compared with clinical monitoring alone. Trial registration Clinical Trials NCT00119093.

Cotrimoxazole prophylaxis by HIV-infected persons in Uganda reduces morbidity and mortality among HIV-uninfected family members.

Background:The effect of cotrimoxazole prophylaxis taken by persons with HIV on community health and antimicrobial resistance is unknown. Objective:To assess the effect of cotrimoxazole prophylaxis taken by persons with HIV on morbidity, mortality, and antimicrobial resistance of diarrheal pathogens infecting their HIV-negative family members. Design:Prospective cohort in rural Uganda. Methods:A total of 879 persons with HIV and 2771 HIV-negative family members received weekly home-visits. After 5 months, persons with HIV received daily cotrimoxazole prophylaxis and households were followed for an average of 17 additional months. Findings:During the study, 224 participants with HIV (25%) and 29 household members (1%) died. Mortality among HIV-negative family members < 10 years old was 63% less during the cotrimoxazole period than before [hazard ratio, 0.37; 95% confidence interval (CI), 0.14–0.95; P = 0.04]. Malaria among family members was less common during cotrimoxazole treatment [incidence rate ratio (IRR), 0.62; CI, 0.53–0.74; P < 0.0001], as were diarrhea (IRR, 0.59; CI, 0.45–0.76; P = 0.0001), and hospitalizations (IRR, 0.57; CI, 0.36–0.92; P = 0.02). Death of a parent with HIV was associated with a threefold increase in mortality among HIV-negative children < 10 years old (hazard ratio, 2.9; CI, 1.1–8.1; P = 0.04). Of 134 bacterial isolates from family members before cotrimoxazole treatment, 89 (66%) were resistant to cotrimoxazole; of 75 recovered during cotrimoxazole treatment, 54 (72%) were resistant (P = 0.41). Interpretation:Cotrimoxazole prophylaxis taken by persons with HIV was associated with decreased morbidity and mortality among family members. Antimicrobial resistance among diarrheal pathogens infecting family members did not increase. Concerns regarding the spread of bacterial resistance should not impede implementation of cotrimoxazole programs.

CD4 cell count and viral load monitoring in patients undergoing antiretroviral therapy in Uganda: cost effectiveness study.

Objective To examine the cost and cost effectiveness of quarterly CD4 cell count and viral load monitoring among patients taking antiretroviral therapy (ART). Design Cost effectiveness study. Setting A randomised trial in a home based ART programme in Tororo, Uganda. Participants People with HIV who were members of the AIDS Support Organisation and had CD4 cell counts <250 ×106 cells/L or World Health Organization stage 3 or 4 disease. Main outcome measures Outcomes calculated for the study period and projected 15 years into the future included costs, disability adjusted life years (DALYs), and incremental cost effectiveness ratios (ICER;

To use or not to use a condom: a prospective cohort study comparing contraceptive practices among HIV-infected and HIV-negative youth in Uganda.

per DALY averted). Cost inputs were based on the trial and other sources. Clinical inputs derived from the trial; in the base case, we assumed that point estimates reflected true differences even if non-significant. We conducted univariate and multivariate sensitivity analyses. Interventions Three monitoring strategies: clinical monitoring with quarterly CD4 cell counts and viral load measurement (clinical/CD4/viral load); clinical monitoring and quarterly CD4 counts (clinical/CD4); and clinical monitoring alone. Results With the intention to treat (ITT) results per 100 individuals starting ART, we found that clinical/CD4 monitoring compared with clinical monitoring alone increases costs by

The estimated burden of HIV/AIDS in Uganda, 2005-2010.

20 458 (£12 780, €14 707) and averts 117.3 DALYs (ICER=

Prevention of mother-to-child transmission and voluntary counseling and testing programme data: what is their utility for HIV surveillance?

174 per DALY). Clinical/CD4/viral load monitoring compared with clinical/CD4 monitoring adds