In the quest for a functional cure or eradication of HIV infection, we need to know how large the reservoirs are from which infection rebounds when treatment is interrupted. To that end, we quantified SIV and HIV tissue burdens in tissues of infected non-human primates and lymphoid tissue (LT) biopsies from infected humans. Before antiretroviral therapy (ART), LTs harbor more than 98 percent of the SIV RNA+ and DNA+ cells. While ART substantially reduced their numbers, vRNA+ cells were still detectable and their persistence was associated with relatively low drug concentrations in LT compared to peripheral blood. Prolonged ART also reduced the level of SIV and HIV-DNA+ cells, but the estimated size of the residual tissue burden of 108 vDNA+ cells that potentially harbor replication competent proviruses, along with the evidence for continuing virus production in LT despite ART, identify two important sources for rebound following treatment interruption. The large sizes of these tissue reservoirs underscore the challenges in developing “HIV cure” strategies that target multiple sources of virus production.

BackgroundPrevention of unplanned pregnancies among HIV-infected individuals is critical to the prevention of mother to child HIV transmission (PMTCT), but its potential has not been fully utilized by PMTCT programmes. The uptake of family planning methods among women in Uganda is low, with current use of family planning methods estimated at 24%, but available data has not been disaggregated by HIV status. The aim of this study was to assess the utilization of family planning and unintended pregnancies among HIV-infected people in Uganda.MethodsWe conducted exit interviews with 1100 HIV-infected individuals, including 441 men and 659 women, from 12 HIV clinics in three districts in Uganda to assess the uptake of family planning services, and unplanned pregnancies, among HIV-infected people. We conducted multivariate analysis for predictors of current use of family planning among women who were married or in consensual union and were not pregnant at the time of the interview.ResultsOne-third (33%, 216) of the women reported being pregnant since their HIV diagnoses and 28% (123) of the men reported their partner being pregnant since their HIV diagnoses. Of these, 43% (105) said these pregnancies were not planned: 53% (80) among women compared with 26% (25) among men. Most respondents (58%; 640) reported that they were currently using family planning methods. Among women who were married or in consensual union and not pregnant, 80% (242) were currently using any family planning method and 68% were currently using modern family planning methods (excluding withdrawal, lactational amenorrhoea and rhythm). At multivariate analysis, women who did not discuss the number of children they wanted with their partners and those who did not disclose their HIV status to sexual partners were less likely to use modern family planning methods (adjusted OR 0.40, range 0.20-0.81, and 0.30, range 0.10-0.85, respectively).ConclusionsThe uptake of family planning among HIV-infected individuals is fairly high. However, there are a large number of unplanned pregnancies. These findings highlight the need for strengthening of family planning services for HIV-infected people.

SummaryBackgroundCo-trimoxazole prophylaxis can reduce mortality from untreated HIV infection in Africa; whether benefits occur alongside combination antiretroviral therapy (ART) is unclear. We estimated the effect of prophylaxis after ART initiation in adults.MethodsParticipants in our observational analysis were from the DART randomised trial of management strategies in HIV-infected, symptomatic, previously untreated African adults starting triple-drug ART with CD4 counts lower than 200 cells per μL. Co-trimoxazole prophylaxis was not routinely used or randomly allocated, but was variably prescribed by clinicians. We estimated effects on clinical outcomes, CD4 cell count, and body-mass index (BMI) using marginal structural models to adjust for time-dependent confounding by indication. DART was registered, number ISRCTN13968779.Findings3179 participants contributed 14 214 years of follow-up (8128 [57%] person-years on co-trimoxazole). Time-dependent predictors of co-trimoxazole use were current CD4 cell count, haemoglobin concentration, BMI, and previous WHO stage 3 or 4 events on ART. Present prophylaxis significantly reduced mortality (odds ratio 0·65, 95% CI 0·50–0·85; p=0·001). Mortality risk reduction on ART was substantial to 12 weeks (0·41, 0·27–0·65), sustained from 12–72 weeks (0·56, 0·37–0·86), but not evident subsequently (0·96, 0·63–1·45; heterogeneity p=0·02). Variation in mortality reduction was not accounted for by time on co-trimoxazole or current CD4 cell count. Prophylaxis reduced frequency of malaria (0·74, 0·63–0·88; p=0·0005), an effect that was maintained with time, but we observed no effect on new WHO stage 4 events (0·86, 0·69–1·07; p=0·17), CD4 cell count (difference vs non-users, −3 cells per μL [−12 to 6]; p=0·50), or BMI (difference vs non-users, −0·04 kg/m2 [−0·20 to 0·13); p=0·68].InterpretationOur results reinforce WHO guidelines and provide strong motivation for provision of co-trimoxazole prophylaxis for at least 72 weeks for all adults starting combination ART in Africa.FundingUK Medical Research Council, the UK Department for International Development, the Rockefeller Foundation, GlaxoSmithKline, Gilead Sciences, Boehringer-Ingelheim, and Abbott Laboratories.

Septicemia is a frequent cause of death in HIV-infected adults in developing countries. Additional prospective studies are needed to determine the etiology of bloodstream infections (BSI) in febrile HIV-infected adults and guide initial evaluation and treatment in this setting. We assessed the prevalence and etiology of community-acquired BSI among 299 consecutive febrile adult medical admissions to Mulago Hospital, Kampala, Uganda, over a 4-month period in 1997. The median age of our patients was 30 years, 159 (53%) were male, and 227 (76%) HIV-1-seropositive. Overall, prevalence of bacteremia or fungemia (1 patient) was 24%. Bacteremia was more frequent in HIV-infected than in uninfected patients (27% versus 15%, respectively; p = .04). Mycobacterium tuberculosis (n = 28), Streptococcus pneumoniae (n = 15) and Salmonella species (n = 13) were the most frequent isolates. All Salmonella and mycobacterial isolates were recovered from HIV-infected patients. Pneumococcal bacteremia was not associated with HIV seropositivity. M. avium complex and M. simiae were isolated from two HIV-infected patients. The rate of mycobacteremia among febrile HIV-infected adults presenting for hospitalization was 13%. Bacteremia and disseminated tuberculosis are frequent causes of morbidity in febrile HIV-infected Ugandan adults. Initial empiric antibiotic coverage in this setting should be targeted toward the pneumococcus and gram-negative enteric bacilli, especially nontyphi Salmonella species. All patients presenting with chronic cough should be evaluated for tuberculosis.

SummaryOBJ ECTIVE To evaluate the quality of pharmaceutical care of malaria for children in eastern Uganda prescribed at government health units and drug shops, and administered by caretakers at home; and to assess its appropriateness in relation to national treatment guidelines, which recommend chloroquine over 3 days. METHODSMETHO DS We followed 463 children under 5 years whose caretakers attended two drug shops and two government health units to seek treatment for fever. The children were examined and the caretakers interviewed on the day of enrolment in the study (day 0), and in their homes on days 3 and 7. Data was collected on drug use prior to attending the shop or health unit, the treatment provided at these study sites, and the administration of drugs at home over the following 3 days. RESULTSRES ULTS Before attending the study sites, 72% of children had already been given some biomedical drugs, and 40% had received the recommended drug, chloroquine. Health workers prescribed chloroquine for 94% of the children, but only 34% of the recommended doses followed guidelines. Two-thirds of the children were prescribed an injection of chloroquine. By day 3, according to caretaker reports, about 38% of the children had received chloroquine in compliance with the instructions given by the health workers and drug shop attendants. Only 28% of the children had received chloroquine at the optimal dose of 20-30 mg/kg recommended by national policy.CONCLUSION CONCLUSION The methods were useful for examining adherence of both caretakers and health care providers to national guidelines and the extent to which caretakers were compliant with providers' prescriptions. Chloroquine and antipyretics were the drugs of choice for fever in these areas of rural eastern Uganda. But children did not receive the recommended dosage of chloroquine because of lack of compliance on the parts of providers as well as users of health care.