Context Therapies to decrease immune activation might be of benefit in slowing HIV disease progression. Objective To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline. Design, Setting, and Patients Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/μL. Intervention Hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks. Main Outcome Measures The primary outcome measure was change in the proportion of activated CD8 cells (measured by the expression of CD38 and HLA-DR surface markers), with CD4 cell count and HIV viral load as secondary outcomes. Analysis was by intention to treat using mixed linear models. Results There was no significant difference in CD8 cell activation between the 2 groups (−4.8% and −4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, −0.6%; 95% CI, −4.8% to 3.6%; P=.80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (−85 cells/μL vs −23 cells/μL at week 48; difference, −62 cells/μL; 95% CI, −115 to −8; P=.03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log10 copies/mL at week 48; difference, 0.38 log10 copies/mL; 95% CI, 0.13 to 0.63; P=.003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P=.03). Conclusion Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in a greater decline in CD4 cell count and increased viral replication. Trial Registration isrctn.org Identifier: ISRCTN30019040

SummaryBackgroundThe effects of antiretroviral therapy on risk of severe bacterial infections in people with high CD4 cell counts have not been well described. In this study, we aimed to quantify the effects of immediate versus deferred ART on the risk of severe bacterial infection in people with high CD4 cell counts in a preplanned analysis of the START trial.MethodsThe START trial was a randomised controlled trial in ART-naive HIV-positive patients with CD4 cell count of more than 500 cells per μL assigned to immediate ART or deferral until their CD4 cell counts were lower than 350 cells per μL. We used Cox proportional hazards regression to model time to severe bacterial infection, which was defined as a composite endpoint of bacterial pneumonia (confirmed by the endpoint review committee), pulmonary or extrapulmonary tuberculosis, or any bacterial infectious disorder of grade 4 severity, that required unscheduled hospital admissions, or caused death. This study is registered with ClinicalTrials.gov, number NCT00867048.FindingsPatients were recruited from April 15, 2009, to Dec 23, 2013. The data cutoff for follow-up was May 26, 2015. Of 4685 HIV-positive people enrolled, 120 had severe bacterial infections (immediate-initiation group n=34, deferred-initiation group n=86; median 2·8 years of follow-up). Immediate ART was associated with a reduced risk of severe bacterial infection compared with deferred ART (hazard ratio [HR] 0·39, 95% CI 0·26–0·57, p<0·0001). In the immediate-initiation group, average neutrophil count over follow-up was 321 cells per μL higher, and average CD4 cell count 194 cells per μL higher than the deferred-initiation group (p<0·0001). In univariable analysis, higher time-updated CD4 cell count (0·78, 0·71–0·85, p=0·0001) was associated with reduced risk of severe bacterial infection. Time-updated neutrophil count was not associated with severe bacterial infection. After adjustment for time-updated factors in multivariable analysis, particularly the CD4 cell count, the HR for immediate-initiation group moved closer to 1 (HR 0·84, 0·50–1·41, p=0·52). These results were consistent when subgroups of the severe bacterial infection composite were analysed separately.InterpretationImmediate ART reduces the risk of several severe bacterial infections in HIV-positive people with high CD4 cell count. This is partly explained by ART-induced increases in CD4 cell count, but not by increases in neutrophil count.FundingNational Institute of Allergy and Infectious Diseases National Institutes of Health, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales, Bundesministerium für Bildung und Forschung, European AIDS Treatment Network, Australian National Health and Medical Research Council, UK National Institute for Health Research and Medical Research Council, Danish National Research Foundation.

Background: Female genital mutilation (FGM) or female circumcision is the removal of variable amounts of tissue from the female external genitalia. It is practised all over the world on very young girls. This study was conducted in Sudan where FGM is a criminal offence and not a religious dictate. We assessed the knowledge, attitudes, and perceptions of this practice among Khartoum university students and compared the differences between male and female student responses. Methods: An anonymised detailed questionnaire was distributed among the university students. In addition to the participant's age, marital status, course studying, details regarding their attitude, knowledge of the practice of FGM, and their own experiences were collected. Results: Of the 500 questionnaires distributed, 414 (82.8%) were returned from 192 (46%) females and 222 (54%) males. 109 (56.8%) of the female respondents were themselves circumcised.18.8% of the male students and 9.4% of the female students thought FGM was recommended by their religion. Only 90 (46.9%) female students compared with 133 (59.9%) male students thought FGM was illegal. Though 16 (8.3%) female respondents thought FGM would increase their chances of marriage, the majority, 166 (74.8%), of the male students would prefer a non-circumcised female. Conclusions: This study shows that 109 (56.8%) female university students who responded were circumcised. Confusing religious messages and ambiguous laws seem to be responsible for the continuation of this practice. The study highlights the partnership that needs to be established between religious leaders and educationalists to end this medieval practice.

Antenatal screening and treatment for sexually transmitted infections (STIs) has shown some benefits in countries where the practice is adopted. To date the prevalence of STIs in the Sudan is unknown. Our aims were to establish the prevalence of STIs among pregnant women in Khartoum (Sudan), to identify any risk factors and to suggest management. One hundred and fifty-one pregnant women were recruited for the study in an antenatal clinic in Khartoum in 1999. The prevalence of Chlamydia trachomatis, HIV, Trichomonas vaginalis, syphilis, Neisseria gonorrhoea and vulvo-vaginal candidiasis among the study population was established; 7.3% of patients suffered multiple infections. No risk factors for acquiring an STI were identified apart from genital ulcer disease. These findings suggest that a syndromic approach for treating STIs during pregnancy might not be possible. We conclude that STIs have a high prevalence among pregnant Sudanese women in Khartoum. The providers of health care in the Sudan need to revise their priority list.

We conducted a cross-sectional survey to determine the prevalence of the human immunodeficiency virus (HIV) among pregnant women attending a major hospital in Kassala state, eastern Sudan. Unlinked anonymous testing of residual blood specimens, which were originally collected for other routine clinical purposes, was performed using rapid immunochromatographic assays. In total, 430 residual blood specimens were consecutively collected over a 6-week period (April-May 2010). Specimens from the antenatal clinic (ANC) constituted 50.7% (218/430) of the total whereas specimens from the labour ward accounted for the remaining 49.3% (212/430). The median age of pregnant women was 29 years (range 16-40). The prevalence of HIV-1 infection was 0.23% (1/430) [95% confidence interval=0.01-1.29%]. The only reactive specimen came from a 20-year-old ANC attendee. We report low HIV prevalence among pregnant women in eastern Sudan but further research is needed to confirm our findings. An integrated framework to diagnose and treat maternal HIV infection should be developed in order to prevent transmission to infants.