Ray Ransom

Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda.

BACKGROUND Prophylaxis with co-trimoxazole (trimethoprim-sulphamethoxazole) is recommended for people with HIV infection or AIDS but is rarely used in Africa. We assessed the effect of such prophylaxis on morbidity, mortality, CD4-cell count, and viral load among people with HIV infection living in rural Uganda, an area with high rates of bacterial resistance to co-trimoxazole. METHODS Between April, 2001, and March, 2003, we enrolled, and followed up with weekly home visits, 509 individuals with HIV-1 infection and their 1522 HIV-negative household members. After 5 months of follow-up, HIV-positive participants were offered daily co-trimoxazole prophylaxis (800 mg trimethoprim, 160 mg sulphamethoxazole) and followed up for a further 1.5 years. We assessed rates of malaria, diarrhoea, hospital admission, and death. FINDINGS Co-trimoxazole was well tolerated with rare (<2% per person-year) adverse reactions. Even though rates of resistance in diarrhoeal pathogens were high (76%), co-trimoxazole prophylaxis was associated with a 46% reduction in mortality (hazard ratio 0.54 [95% CI 0.35-0.84], p=0.006) and lower rates of malaria (multivariate incidence rate ratio 0.28 [0.19-0.40], p<0.0001), diarrhoea (0.65 [0.53-0.81], p<0.0001), and hospital admission (0.69 [0.48-0.98], p=0.04). The annual rate of decline in CD4-cell count was less during prophylaxis than before (77 vs 203 cells per microL, p<0.0001), and the annual rate of increase in viral load was lower (0.08 vs 0.90 log(10) copies per mL, p=0.01). INTERPRETATION Daily co-trimoxazole prophylaxis was associated with reduced morbidity and mortality and had beneficial effects on CD4-cell count and viral load. Co-trimoxazole prophylaxis is a readily available, effective intervention for people with HIV infection in Africa.

Adherence to antiretroviral therapy in a home-based AIDS care programme in rural Uganda

BACKGROUND Poverty and limited health services in rural Africa present barriers to adherence to antiretroviral therapy that necessitate innovative options other than facility-based methods for delivery and monitoring of such therapy. We assessed adherence to antiretroviral therapy in a cohort of HIV-infected people in a home-based AIDS care programme that provides the therapy and other AIDS care, prevention, and support services in rural Uganda. METHODS HIV-infected individuals with advanced HIV disease or a CD4-cell count of less than 250 cells per muL were eligible for antiretroviral therapy. Adherence interventions included group education, personal adherence plans developed with trained counsellors, a medicine companion, and weekly home delivery of antiretroviral therapy by trained lay field officers. We analysed factors associated with pill count adherence (PCA) of less than 95%, medication possession ratio (MPR) of less than 95%, and HIV viral load of 1000 copies per mL or more at 6 months (second quarter) and 12 months (fourth quarter) of follow-up. FINDINGS 987 adults who had received no previous antiretroviral therapy (median CD4-cell count 124 cells per muL, median viral load 217,000 copies per mL) were enrolled between July, 2003, and May, 2004. PCA of less than 95% was calculated for 0.7-2.6% of participants in any quarter and MPR of less than 95% for 3.3-11.1%. Viral load was below 1000 copies per mL for 894 (98%) of 913 participants in the second quarter and for 860 (96%) of 894 of participants in the fourth quarter. In separate multivariate models, viral load of at least 1000 copies per mL was associated with both PCA below 95% (second quarter odds ratio 10.6 [95% CI 2.45-45.7]; fourth quarter 14.5 [2.51-83.6]) and MPR less than 95% (second quarter 9.44 [3.40-26.2]; fourth quarter 10.5 [4.22-25.9]). INTERPRETATION Good adherence and response to antiretroviral therapy can be achieved in a home-based AIDS care programme in a resource-limited rural African setting. Health-care systems must continue to implement, evaluate, and modify interventions to overcome barriers to comprehensive AIDS care programmes, especially the barriers to adherence with antiretroviral therapy.

Effect of co-trimoxazole prophylaxis, antiretroviral therapy, and insecticide-treated bednets on the frequency of malaria in HIV-1-infected adults in Uganda: a prospective cohort study

BACKGROUND HIV-1 and malaria are common infections in Africa, and cause substantial morbidity and mortality. HIV infection has been associated with an increased incidence of malaria, and more severe disease. Our aim was to assess the effect of antiretroviral treatment (ART) on the frequency of clinical malaria in people with HIV, and to measure the additive effects of co-trimoxazole (trimethoprim and sulfamethoxazole) prophylaxis, ART, and insecticide-treated bednets. METHODS In 2001, we enrolled 466 HIV-infected individuals aged 18 years or older in Uganda in a prospective cohort study that provided co-trimoxazole prophylaxis to 399 participants after 5 months of no intervention. In 2003, we enrolled 138 survivors from the initial study, and 897 new participants from the same community, to take antiretroviral therapy (ART) in addition to co-trimoxazole prophylaxis. The ART was in most cases a combination of stavudine, lamivudine, and nevirapine or efavirenz. In 2004, we also gave participants insecticide-treated bednets. Households were visited weekly by study staff to record fever, illness, or death in the preceding 7 days. In cases of reported fever in the previous 2 days, we took blood to test for malaria parasites. We compared the frequency of clinical malaria, adjusting for CD4-cell count, age, sex, and season. FINDINGS 1035 individuals were given co-trimoxazole and ART (median age 38 years, 74% female, and median CD4-cell count 124 cells/microL); 985 of these, plus four new participants, received co-trimoxazole, ART, and bednets. There were 166 cases of clinical malaria in the study. Compared with a baseline malaria incidence of 50.8 episodes per 100 person-years, co-trimoxazole prophylaxis was associated with 9.0 episodes per 100 person-years (adjusted incidence rate ratio [IRR] 0.24, 95% CI 0.15-0.38); ART and co-trimoxazole with 3.5 episodes per 100 person-years (0.08, 0.04-0.17); and co-trimoxazole, ART, and bednets with 2.1 episodes per 100 person-years (0.05, 0.03-0.08). Malaria incidence was significantly lower during ART and co-trimoxazole than during co-trimoxazole alone (IRR 0.36 [95% CI 0.18-0.74], p=0.0056). INTERPRETATION A combination of co-trimoxazole, antiretroviral therapy, and insecticide-treated bednets substantially reduced the frequency of malaria in adults with HIV.

Asymptomatic serum cryptococcal antigenemia and early mortality during antiretroviral therapy in rural Uganda

Objective  To evaluate the association between a positive serum cryptococcal antigen (CRAG) test at baseline and mortality during the first 12 weeks on antiretroviral therapy (ART). Cryptococcal meningitis is a leading cause of HIV‐related mortality in Africa, but current guidelines do not advocate CRAG testing as a screening tool.

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.

Home-based HIV testing and counseling in rural and urban Kenyan communities.

Background:In sub-Saharan Africa, most people with HIV do not know they are infected. Methods:We conducted door-to-door home-based testing and counseling (HBTC) in rural western Kenya (Lwak) and an informal urban settlement in Nairobi (Kibera) in 2008. After consent, eligible persons (adults and adolescents aged 13 years or older and children aged 12 years or younger, whose biologic mother was HIV-infected or deceased) received parallel fingerstick HIV rapid testing and counseling. Persons newly diagnosed with HIV were referred to care services, fingerstick blood for CD4 testing was collected, and a one-month follow-up home visit was conducted. Results:Among 24,450 people who were offered HBTC, 19,966 (81.7%) accepted; 65.4% of whom were HIV-tested for the first time. Prevalence in adults aged 18 years or older being HIV-tested for the first time was 13.5% (12.6%, Kibera; 14.2%, Lwak). Among adults who reported a previously negative test, HIV prevalence was 7.4% (7.2%, Kibera; 7.6%, Lwak). Among all persons with HIV in these communities, two-thirds were newly diagnosed through HBTC. Median CD4 count among newly diagnosed adults was 403 [interquartile range (IQR) = 252–594]. Among couples, 38.0% in Kibera and 51.7% in Lwak were counseled together. Among HIV-infected people in a couple, 34.6% had an HIV-uninfected partner. Among newly diagnosed HIV-infected persons, at the one-month follow-up visit, 53.6% in Kibera and 43.6% in Lwak reported having visited an HIV patient support center. Conclusions:HBTC acceptance was high and most HIV-infected persons did not previously know they had HIV. HBTC can be an effective strategy for early HIV diagnosis and treatment referral.

Ebola and Its Control in Liberia, 2014–2015

Several factors explain the successful response to the outbreak in this country.