SummaryBackground 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 µL, 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.

Diarrhea is frequent among persons infected with human immunodeficiency virus (HIV) but few interventions are available for people in Africa. We conducted a randomized controlled trial of a home-based, safe water intervention on the incidence and severity of diarrhea among persons with HIV living in rural Uganda. Between April 2001 and November 2002, households of 509 persons with HIV and 1,521 HIV-negative household members received a closed-mouth plastic container, a dilute chlorine solution, and hygiene education (safe water system [SWS]) or simply hygiene education alone. After five months, HIV-positive participants received daily cotrimoxazole prophylaxis (160 mg of trimethoprim and 800 mg of sulfamethoxazole) and were followed for an additional 1.5 years. Persons with HIV using SWS had 25% fewer diarrhea episodes (adjusted incidence rate ratio [IRR] = 0.75, 95% confidence interval [CI] = 0.59-0.94, P = 0.015), 33% fewer days with diarrhea (IRR = 0.67, 95% CI = 0.48-0.94, P = 0.021), and less visible blood or mucus in stools (28% versus 39%; P < 0.0001). The SWS was equally effective with or without cotrimoxazole prophylaxis (P = 0.73 for interaction), and together they reduced diarrhea episodes by 67% (IRR = 0.33, 95% CI = 0.24-0.46, P < 0.0001), days with diarrhea by 54% (IRR = 0.46, 95% CI = 0.32-0.66, P < 0.0001), and days of work or school lost due to diarrhea by 47% (IRR = 0.53, 95% CI = 0.34-0.83, P < 0.0056). A home-based safe water system reduced diarrhea frequency and severity among persons with HIV living in Africa and large scale implementation should be considered.

BackgroundEarly and accurate diagnosis of malaria followed by prompt treatment reduces the risk of severe disease in malaria endemic regions. Presumptive treatment of malaria is widely practised where microscopy or rapid diagnostic tests (RDTs) are not readily available. With the introduction of artemisinin-based combination therapy (ACT) for treatment of malaria in many low-resource settings, there is need to target treatment to patients with parasitologically confirmed malaria in order to improve quality of care, reduce over consumption of anti-malarials, reduce drug pressure and in turn delay development and spread of drug resistance. This study evaluated the effect of malaria RDTs on health workers' anti-malarial drug (AMD) prescriptions among outpatients at low level health care facilities (LLHCF) within different malaria epidemiological settings in Uganda.MethodsAll health workers (HWs) in 21 selected intervention (where RDTs were deployed) LLHF were invited for training on the use RDTs. All HWs were trained to use RDTs for parasitological diagnosis of all suspected malaria cases irrespective of age. Five LLHCFs with clinical diagnosis (CD only) were included for comparison. Subsequently AMD prescriptions were compared using both a 'pre - post' and 'intervention - control' analysis designs. In-depth interviews of the HWs were conducted to explore any factors that influence AMD prescription practices.ResultsA total of 166,131 out-patient attendances (OPD) were evaluated at 21 intervention LLHCFs. Overall use of RDTs resulted in a 38% point reduction in AMD prescriptions. There was a two-fold reduction (RR 0.62, 95% CI 0.55-0.70) in AMD prescription with the greatest reduction in the hypo-endemic setting (RR 0.46 95% CI 0.51-0.53) but no significant change in the urban setting (RR1.01, p-value = 0.820). Over 90% of all eligible OPD patients were offered a test. An average of 30% (range 25%-35%) of the RDT-negative fever patients received AMD prescriptions. When the test result was negative, children under five years of age were two to three times more likely (OR 2.6 p-value <0.001) to receive anti-malarial prescriptions relative to older age group. Of the 63 HWs interviewed 92% believed that a positive RDT result confirmed malaria, while only 49% believed that a negative RDT result excluded malaria infection.ConclusionUse of RDTs resulted in a 2-fold reduction in anti-malarial drug prescription at LLHCFs. The study demonstrated that RDT use is feasible at LLHCFs, and can lead to better targetting of malaria treatment. Nationwide deployment of RDTs in a systematic manner should be prioritised in order to improve fever case management. The process should include plans to educate HWs about the utility of RDTs in order to maximize acceptance and uptake of the diagnostic tools and thereby leading to the benefits of parasitological diagnosis of malaria.

BackgroundAntiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated.MethodsT-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199) cells/μl], N = 34 ], optimal [282 (200-415) cells/μl, N = 64] and super-optimal [528 (416-878) cells/μl, N = 30].ResultsBoth CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014)]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+) was higher among suboptimal relative to optimal (P < 0.001) and super-optimal responders (P < 0.001). T-cell exhaustion was significantly associated with suboptimal responders [AOR, 1.5 (95%CI, 1.1-2.1), P = 0.022].ConclusionT-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART.

BackgroundThe UNAIDS 90–90-90 strategy clearly stipulates that 90% of all people on antiretroviral therapy (ART) should have a suppressed viral load. Intensified adherence counselling (IAC) was recently recommended by WHO to improve viral suppression among ART-treated paediatric and adolescent clients with virological failure. This paper describes the implementation and outcomes of IAC in the first year of implementation in a public ART program, to inform strategic interventions to reach the “third 90” among children.MethodsA retrospective chart review was conducted for all children aged 9 months to 19 years with HIV viral loads (VL) ≥ 1000 copies/ml at 15 public health facilities from June 2015–December 2016. Data on initial VL test results, IAC sessions, repeat VL test results, and ART regimen switch were abstracted and analysed for completion of IAC and viral suppression after IAC.ResultsA total of 449 children had a detectable viral load above 1000 copies/ml, after an average of 3.5 years (SD 5.8) years of ART. 192 (43%) were 10–20 years of age, and 320 (71%) were receiving Nevirapine-based ART regimen. Out of 345 (77%) who completed the recommended three IAC sessions, 62 (23%) achieved viral suppression following IAC. The mean time from 1st to 3rd IAC session was 113 (SD 153) days and 172 (50%) of the children had completed the three sessions within 200 days.ConclusionSuppression rates were low among ART-treated children with virological failure that completed the recommended three IAC sessions. As we move towards having 90% of ART-treated children and adolescents achieve and maintain viral suppression, there is need to re-evaluate the implementation of IAC among children and adolescents to consider both psychosocial and biological factors such as resistance testing for those with multiple detectable viral loads.

HIV testing is an entry point to comprehensive HIV/AIDS prevention and care. In Uganda, Routine Testing and Counseling for HIV (RTC) is not widely offered as part of standard medical care in acute care settings. This study determined the acceptance of RTC in a medical emergency setting at Mulago national referral hospital. We interviewed 233 adult patients who were offered HIV testing. Overall, 83% were unaware of their HIV serostatus and 88% of these had been to a health unit in the previous six months. Of the 208 eligible for HIV testing, 95% accepted to test. Half the patients were HIV infected and 77% of these were diagnosed during the study. HIV testing was highly acceptable and detected a significant number of undiagnosed HIV infections. We recommend adoption of RTC as standard of care in the medical emergency unit in order to scale HIV diagnosis and linkage to HIV/AIDS care.

Despite scale up of perinatal prevention of mother-to-child transmission (PMTCT) of HIV interventions, postnatal continuity of comprehensive HIV/AIDS care, for both the mother and baby, remains a challenge in developing countries. We determined adherence to the postnatal PMTCT program (PN-PMTCT) and the associated factors among mothers at a public urban hospital in Uganda. We interviewed HIV-positive postnatal mothers on discharge and we determined adherence to PN-PMTCT by the proportion of mothers that honored their return appointments by the end of eight weeks postpartum. We had focus group discussions to assess factors that influence adherence to PN-PMTCT. Of 289 mothers, only 110 (38%) adhered to PN-PMTCT. Previous attendance of a routine postnatal review and having access to a phone were significantly associated with adherence to PMTCT among mothers older than 25 years (odds ratio (OR) 3.6 (95% confidence interval (CI); 1.2-10.4)) and (OR 3.1 (95% CI; 1.3-7.1)), respectively. On the other hand, Christianity (OR 3.2 (95% CI; 1.1-9.0)) was significantly associated with adherence to PN-PMTCT among mothers below 25 years of age. Mothers' perceived benefits of the PN-PMTCT program, easy access to the program, and presence of social support from a spouse were important motivators for mothers to adhere to PN-PMTCT. Even with improved antenatal and intra-partum PMTCT services, only a third of the HIV-infected mothers adhered to the PN-PMTCT program. Mothers who previously attended a routine postnatal care were 3.6 fold more likely to adhere to PN-PMTCT. We recommend strategies to increase mothers' adherence to PN-PMTCT interventions in order to increase access to HIV/AIDS care for mothers and children in sub-Saharan Africa.

BackgroundThe increased immune activation and inflammation of chronic HIV-infection and the characteristic dyslipidemias associated with HIV infection and antiretroviral therapy (ART) contribute to an increased risk of atherosclerotic vascular disease among HIV-infected adults. There is an emerging need to understand determinants of cardiovascular disease (CVD) among individuals aging with HIV in sub-Saharan Africa. We determined the prevalence of subclinical atherosclerosis [carotid intima media thickness (CIMT) ≥0.78 mm] and its correlation with traditional CVD risk factors among HIV-infected adults.MethodsIn a cross-sectional study, HIV-infected adults (ART-naïve and ART-treated) were consecutively selected from patients' enrollment registers at two large HIV clinics at Mulago Hospital, Kampala, Uganda. We measured traditional CVD risk factors including age, biophysical profile, fasting blood sugar and serum lipid profile as well as biomarkers of inflammation. High resolution ultrasound was used to measure common carotid CIMT.ResultsOf 245 patients, Median age [Interquartile range (IQR)] 37 years (31–43), 168 (69%) were females; and 100 (41%) were ART-treated for at least 7 years. Overall, 34/186 (18%) had subclinical atherosclerosis; of whom 15/108 (14%) were ART-naïve whereas 19/78 (24%) were ART-treated. Independent predictors of subclinical atherosclerosis included age [odds ratio (OR) 1.83 per 5-year increase in age; 95% confidence interval (CI) 1.24–2.69; p = 0.002], body mass index (BMI); OR 1.15; CI 1.01–1.31; p = 0.041 and high low density lipoprotein (LDL) [OR 2.99; CI 1.02–8.78, p = 0.046]. High sensitivity C-reactive protein (hsCRP) was positively correlated with traditional cardio-metabolic risk factors including waist circumference (r = 0.127, p = 0.05), triglycerides (r = 0.19, p = 0.003) and Total Cholesterol: High Density Lipoprotein ratio (TC:LDL) (r = 0.225, p<0.001).ConclusionThe prevalence of subclinical atherosclerosis was 18% among HIV-infected adults in Uganda. Traditional CVD risk factors were associated with subclinical atherosclerosis. We recommend routine assessment of traditional CVD risk factors within HIV care and treatment programs in sub-Saharan Africa.