There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future. This article has not been written or reviewed by Nature editors. Nature accepts no responsibility for the accuracy of the information provided.

Alcohol use by persons living with HIV/AIDS (PLWHA) negatively impacts the public health benefits of antiretroviral therapy (ART). Using a standardized alcohol assessment tool, we estimate the prevalence of alcohol use, identify associated factors, and test the association of alcohol misuse with sexual risk behaviors among PLWHA in Uganda. A cross-section of PLWHA in Kampala were interviewed regarding their sexual behavior and self-reported alcohol consumption in the previous 6 months. Alcohol use was assessed using the alcohol use disorders identification test (AUDIT). Gender-stratified log binomial regression analyses were used to identify independent factors associated with alcohol misuse and to test whether alcohol misuse was associated with risky sexual behaviors. Of the 725 subjects enrolled, 235 (33%) reported any alcohol use and 135 (18.6%) reported alcohol misuse, while 38 (5.2%) drank hazardous levels of alcohol. Alcohol misuse was more likely among subjects not yet on ART (adjusted prevalence ratio [aPR] was 1.65 p=0.043 for males and 1.79, p=0.019 for females) and those with self-reported poor adherence (aPR for males=1.56, p=0.052, and for females=1.93, p=0.0189). Belonging to Pentecostal or Muslim religious denominations was protective against alcohol misuse compared to belonging to Anglican and Catholic denominations in both sexes (aPR=0.11 for men, p<0.001, and aPR=0.32 for women, p=0.003). Alcohol misuse was independently associated with reporting risky sexual behaviors (aPR=1.67; 95% CI: 1.07–2.60, p=0.023) among males, but not significant among females (aPR=1.29; 95% CI: 0.95–1.74, p=0.098). Non-disclosure of HIV positive status to sexual partner was significantly associated with risky sex in both males (aPR=1.69; p=0.014) and females (aPR 2.45; p<0.001). Alcohol use among PLWHA was high, and was associated with self-reported medication non-adherence, non-disclosure of HIV positive status to sexual partner(s), and risky sexual behaviors among male subjects. Interventions targeting alcohol use and the associated negative behaviors should be tested in this setting.

We evaluated the efficacy of a brief motivational intervention (MI) counseling in reducing alcohol consumption among persons living with HIV/AIDS in Kampala, Uganda. Persons living with HIV/AIDS with Alcohol Use Disorders Identification Tool (AUDIT) score ≥3 points were randomized to either standardized positive prevention counseling alone or in combination with alcohol brief MI counseling. The mean change in AUDIT-C scores over 6 months was compared by treatment arm. The mean (standard deviation [SD]) AUDIT-C scores were 6.3 (2.3) and 6.8 (2.3) for control and MI arms (P = .1) at baseline, respectively, and change in mean AUDIT-C score was not statistically different between arms over the 6 months (P = .8). However, there was a statistically significant decrease in mean AUDIT-C score (−1.10; 95% confidence interval: −2.19 to −0.02, P = .046) among women in the MI arm. There was a nondifferential reduction in alcohol consumption overall, but MI appeared effective among women only. Studies with more than 1 counseling session and evaluation of gender differences in treatment response are needed.

Cryptococcal disease remains an important cause of morbidity and mortality in HIV-infected individuals in sub-Saharan Africa, despite the introduction of antiretroviral therapy. We studied fluconazole as primary prophylaxis against cryptococcal disease in patients awaiting or starting antiretroviral therapy in Uganda. In this prospective, double-blind randomised controlled trial, we enrolled HIV-positive adults with CD4 counts less than 200 cells per μL, cryptococcal antigen (CrAg)-negative, naive for antiretroviral therapy, and coming from five local AIDS organisations in Masaka district, Uganda. Enrolment took place between Sept 14, 2004, and Feb 1, 2008. Participants were randomly allocated to placebo or 200 mg fluconazole three times per week (1:1) in blocks of 40. Randomisation was done with ralloc procedure in Stata. Participants were reviewed after 4 weeks and referred for antiretroviral therapy, then seen every 8 weeks. Participants discontinued trial treatment when CD4 counts reached 200 cells per μL (median 197 days). Primary endpoints were invasive cryptococcal disease and all-cause mortality. Secondary endpoints were time to first episode and incidence of oesophageal candidosis, time to first episode and incidence of oropharyngeal or vaginal candidosis, and time to first hospital admission or death. The primary safety endpoint was cessation of trial drug because of transaminase concentrations higher than five times the upper limit of normal (ULN), or other major adverse events. Analyses were done by intention to treat and included all participants enrolled in the trial. Participants and researchers were masked to group assignment. This trial is registered with controlled-trials.com, number ISRCTN 76481529. Of 1519 individuals enrolled, 760 participants received fluconazole and 759 received placebo. 19 developed cryptococcal disease, one in the fluconazole group and 18 in the placebo group (p=0·0001); adjusted HR (aHR) 18·7 (95% CI 2·5-140·7). One case of cryptococcal disease could be prevented by treating 44·6 patients with baseline CD4 counts lower than 200 cells per μL. Fluconazole was effective against cryptococcal disease both before (aHR=11·0 [1·4-85·3]) and after start of antiretroviral therapy (no cases in fluconazole vs seven cases on placebo). Seven participants died from cryptococcal disease, none in the fluconazole group. All-cause mortality (n=189) did not differ between the two groups (p=0·46). Fluconazole reduced the time to first episode of oesophageal, and oropharyngeal and vaginal candidosis, as well as the incidence of all candidosis (p5×ULN) was similar between groups (aHR=0·94 [0·65-1·35]). Fluconazole was safe and effective as primary prophylaxis against cryptococcal disease, both before and during early antiretroviral treatment. Cryptococcal infection was less common than anticipated because of the rapid commencement of antiretroviral therapy and exclusion of those with positive CrAg. In patients with negative CrAg on screening, fluconazole prophylaxis can prevent cryptococcal disease while waiting for and in the early weeks of antiretroviral therapy, particularly in those with CD4 counts of less than 100 cells per μL. Medical Research Council, UK, and Rockefeller Foundation.

This study aimed to measure symptom burden prior to antitetroviral therapy (ART) initiation in a population of adults with low CD4 presenting for human immunodeficiency virus (HIV) care and treatment in Uganda, and to explore the relationship between World Health Organization (WHO) stage, CD4 count, and symptomatology. HIV-infected, ART-naïve adults with CD4 less than 200 cells per microliter referred from voluntary testing and counseling services in rural Uganda for potential enrollment into a large double-blinded placebo-controlled trial were invited to completed the Memorial Symptom Assessment Scale-Short Form (MSAS-SF). This is a validated symptom assessment tool that records the presence and severity of 37 physical and 4 psychological symptoms. Two hundred twelve subjects were enrolled. The mean total number of symptoms was 14.0 (standard deviation [SD] = 6). The 10 most common symptoms were pain (76%), weight loss (70%), itching (67%), feeling drowsy/tired (61%), and lack of energy (61%), numbness /tingling in hands or feet (57%), cough (53%) skin changes (52%), worry (51%), and lack of appetite (49%). The median number of symptoms was not associated with WHO stage CD4 count group. This study demonstrates that the burden of HIV-related symptoms in individuals presenting for care in Uganda is significant and debilitating.