HIV-infected Ugandan Adults Research Articles

Qualitative study of changes in alcohol use among HIV-infected adults entering care and treatment for HIV/AIDS in rural southwest Uganda.

Alcohol has a substantial negative impact on the HIV epidemic in sub-Saharan Africa, particularly in Uganda, where heavy alcohol consumption is common. Using a content analytic approach, this qualitative study characterizes changes in alcohol use among 59 HIV-infected Ugandan adults (>18 years old), who reported any alcohol use in the previous year as they entered HIV care. Most participants reported attempting to cease or reduce alcohol intake over the study period. Reasons for decreased use included advice from clinicians, interference with social obligations, threats to financial security, and negative impact on social standing. Participants reported difficulty abstaining from alcohol, with incentives to continue drinking including desire for social inclusion, stress relief, and enjoyment of alcohol. These contrasting incentives created a moral quandary for some participants, who felt ‘pulled’ between ‘good’ and ‘bad’ influences. Results suggest brief interventions addressing self-identified obstacles to change may facilitate long-term reductions in drinking in this population.

Point-of-care lateral flow assays for tuberculosis and cryptococcal antigenuria predict death in HIV infected adults in Uganda.

BackgroundMortality in hospitalized, febrile patients in Sub-Saharan Africa is high due to HIV-infected, severely immunosuppressed patients with opportunistic co-infection, particularly disseminated tuberculosis (TB) and cryptococcal disease. We sought to determine if a positive lateral flow assay (LFA) result for urine lipoarabinomannan (LAM) and cryptococcal antigenuria was associated with mortality.Methods351 hospitalized, HIV-positive adults with symptoms consistent with TB and who were able to provide both urine and sputum specimens were prospectively enrolled at Mulago National Referral Hospital in Uganda as part of a prospective accuracy evaluation of the lateral flow Determine TB LAM test. Stored frozen urine was retrospectively tested for cryptococcal antigen (CRAG) using the LFA. We fitted a multinomial logistic regression model to analyze factors associated with death within 2 months after initial presentation.ResultsThe median CD4 of the participants was 57 (IQR: 14–179) cells/µl and 41% (145) were microbiologically confirmed TB cases. LAM LFA was positive in 38% (134), 7% (25) were CRAG positive, and 43% (151) were positive for either test in urine. Overall, 21% (75) died within the first 2 months, and a total of 32% (114) were confirmed dead by 6 months. At 2 months, 30% of LAM or CRAG positive patients were confirmed dead compared to 15.0% of those who were negative. In an adjusted model, LAM or CRAG positive results were associated with an increased risk of death (RRR 2.29, 95% CI: 1.29, 4.05; P = 0.005).ConclusionsIn hospitalized HIV-infected patients, LAM or CRAG LFA positivity was associated with subsequent death within 2 months. Further studies are warranted to examine the impact of POC diagnostic ‘test and treat’ approach on patient-centered outcomes.

CD4 T-cell activation and reduced regulatory T-cell populations are associated with early development of cataracts among HIV-infected adults in Uganda

BackgroundCataracts contribute 12% of visual loss among HIV-infected adults in Uganda. Immuno-pathogenesis of cataracts may differ among HIV-infected individuals; thus the need for innovative therapeutic interventions among HIV-infected adults. MethodsIn a laboratory based case-control study, nested in a clinical/surgical community outreach camp, 50 adults with cataracts eligible for surgery were selected consecutively. HIV testing was done for individuals with unknown HIV sero-status. Peripheral Blood Mononuclear Cells (PBMC) were collected from all HIV-positive-adults-with-cataracts (cases) and HIV-negative-adults-with-cataracts (comparative group) and age-matched HIV-negative and HIV-positive-adults-without-cataracts (comparative group). Treg were measured as CD3+CD4+FoxP3+CD25+Bright and immune activation as CD3+CD4+CD38+HALDR+ using a Facs Canto II flowcytometer. Mann Whitney test was used to compare expression among the four groups. ResultsOf 50 adults operated for cataracts, 24 (48%) were female, 25 (50%) were HIV-positive. HIV-positive-individuals had cataracts earlier [median; Inter-quartile Range (IQR); 49 (44–53) years] than HIV-negative [70 (IQR 59–75) years]; p=0.0005. Treg were lower among individuals with cataracts irrespective of HIV status; p=0.001; but comparable among younger HIV-positive and elderly HIV-negative with cataracts; p=0.301. Immune activation levels were comparable among HIV-positive and HIV-negative individuals with cataracts. However, HIV-positive-individuals with cataracts expressed higher levels of immune activation than HIV-positive-individuals without cataracts; p=0.012 and HIV-negative-individuals-with-cataracts expressed higher levels of immune activation that HIV-negative-without-cataracts; p<0.0001. ConclusionCD4 T-cell activation and reduced regulatory T-cell populations were associated with cataracts among adults aging with HIV. We recommend studies on clinical relevance of immune modulation in the prevention of early development of cataracts among adults aging with HIV in Africa.

Point-of-Care C-Reactive Protein Testing to Facilitate Implementation of Isoniazid Preventive Therapy for People Living With HIV

Symptom-based tuberculosis screening identifies less than one-third of eligible HIV-infected patients as candidates for isoniazid preventive therapy (IPT). We evaluated whether testing for C-reactive protein (CRP) improves patient selection for IPT. We measured CRP levels (normal <10 mg/L) using a point-of-care (POC) assay on stored serum samples from HIV-infected Ugandan adults initiating antiretroviral therapy. We assessed diagnostic accuracy in reference to baseline tuberculosis status adjudicated by an expert committee and calculated net reclassification improvement to quantify the incremental discriminatory benefit of POC-CRP in determining IPT eligibility compared to the World Health Organization (WHO) symptom screen. Of 201 patients (median CD4 cell count, 137 cells/μL; interquartile range, 83-206), 5 (2.5%) had tuberculosis. Compared to the WHO symptom screen, POC-CRP had similar sensitivity (100% vs. 80%, P = 0.30) but greater specificity (21% vs. 87%, P < 0.0001) for tuberculosis. If based on the WHO symptom screen, no patients with tuberculosis but only 42 of 196 patients without tuberculosis would have been considered IPT eligible. If POC-CRP were used instead, 1 patient with tuberculosis (reclassification of cases, -20%; P = 0.32) and 129 patients without tuberculosis (reclassification of noncases, +66%; P < 0.001) would have been reclassified as IPT eligible, a net reclassification improvement of 46% (P = 0.03). In addition, POC-CRP testing would have reduced the proportion of patients without active tuberculosis requiring confirmatory tuberculosis testing (87% vs. 21%, P < 0.0001). POC-CRP testing increased more than 4-fold the proportion of HIV-infected adults immediately identified as IPT eligible and decreased the proportion of patients requiring referral for further tuberculosis diagnostic testing. POC-CRP testing could substantially improve implementation of tuberculosis screening guidelines.

Developing a culturally sensitive group support intervention for depression among HIV infected and non-infected Ugandan adults: A qualitative study

BackgroundDepression is ranked first among neuropsychiatric diseases that contribute to the burden of disease in low- and middle-income countries. However, access to antidepressants is limited and there is a dearth of locally developed psychotherapeutic interventions targeted to treat depression. AimWe aimed to obtain information on the cultural understanding of depression symptoms, complications and treatment methods used in post-conflict communities in northern Uganda in order to inform the development of an indigenous group support intervention to treat depression. MethodsFocus group discussions (FGDs) were conducted with a total of 110 men and women aged 19–68 years. FDGs took place in a private space, lasted about 2–3h and were conducted in the local language for patients and their caregivers and in English for health workers. Interview transcripts from the FGDs were reviewed for accuracy, translated into English and transcribed. QRS Nvivo 10 qualitative data analysis software was used for coding and thematic analysis. ResultsOur study revealed community misperceptions about etiology, presentation and treatment of depression. Regardless of HIV status, most FGD participants who were not health workers linked depression symptoms to HIV infection. Although there were concerns about confidentiality of issues disclosed, many FGD participants were supportive of a group support intervention, tailored to their gender and age, that would not only focus on treating depression but also provided them with skills to improve their livelihoods. Simple CBT techniques were deemed culturally appropriate and acceptable. LimitationGeneralizability of study findings may be limited given that the sample was primarily of Luo ethnicity yet there are different ethnic populations in the region. ConclusionLocal communities can directly inform intervention content. The participants׳ preferences confirmed the need for a gender-specific intervention for depression that extends beyond medications and empowers them emotionally, socially and economically.

Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda

ObjectivesWe investigated phenotypic and genotypic resistance after 2 years of first-line therapy with two HIV treatment regimens in the absence of virological monitoring.MethodsNORA [Nevirapine OR Abacavir study, a sub-study of the Development of AntiRetroviral Therapy in Africa (DART) trial] randomized 600 symptomatic HIV-infected Ugandan adults (CD4 cell count <200 cells/mm3) to receive zidovudine/lamivudine plus abacavir (cABC arm) or nevirapine (cNVP arm). All virological tests were performed retrospectively, including resistance tests on week 96 plasma samples with HIV RNA levels ≥1000 copies/mL. Phenotypic resistance was expressed as fold-change in IC50 (FC) relative to wild-type virus.ResultsHIV-1 RNA viral load ≥1000 copies/mL at week 96 was seen in 58/204 (28.4%) cABC participants and 21/159 (13.2%) cNVP participants. Resistance results were available in 35 cABC and 17 cNVP participants; 31 (89%) cABC and 16 (94%) cNVP isolates had a week 96 FC below the biological cut-off for tenofovir (2.2). In the cNVP arm, 16/17 participants had resistance mutations synonymous with high-level resistance to nevirapine and efavirenz; FC values for etravirine were above the biological cut-off in 9 (53%) isolates. In multivariate regression models, K65R, Y115F and the presence of thymidine analogue-associated mutations were associated with increased susceptibility to etravirine in the cABC arm.ConclusionsOur data support the use of tenofovir following failure of a first-line zidovudine-containing regimen and shed further light on non-nucleoside reverse transcriptase inhibitor hypersusceptibility.

Subclinical Atherosclerosis among HIV-Infected Adults Attending HIV/AIDS Care at Two Large Ambulatory HIV Clinics in Uganda

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.

CD4 T-cell Activation and Reduced Regulatory T-cell Populations are Associated with Early Development of Cataracts among HIV-infected Adults in Uganda

CD4 T-cell Activation and Reduced Regulatory T-cell Populations are Associated with Early Development of Cataracts among HIV-infected Adults in Uganda

Severe mental illness at ART initiation is associated with worse retention in care among HIV‐infected Ugandan adults

The impact of severe mental illness (SMI) on retention in HIV care remains uncertain. We aimed to measure the association between SMI at antiretroviral therapy (ART) initiation and subsequent retention in care in HIV-infected Ugandan adults. We conducted cohort study of 773 patients who initiated ART between January 2005 and July 2009 at the Butabika HIV clinic in Kampala, Uganda. SMI was defined as any clinically diagnosed organic brain syndrome, affective disorder or psychotic disorder. We used Kaplan-Meier and Cox proportional hazards analysis to evaluate the association between SMI and retention in care. The prevalence of SMI at ART initiation was 23%. Patients with SMI at baseline were similar to those without SMI in terms of age (median [IQR]: 35 [28-40] vs. 35 [30-40], P = 0.03), sex (36% vs. 35% female, P = 0.86) and baseline CD4+ T-cell count (112 [54-175] vs. 120 [48-187] cells/mm3, P = 0.86). At 12 months after ART initiation, Kaplan-Meier estimates of continuous retention in care were 65% (95% confidence interval, CI: 31-39%) among patients without SMI, vs. 47% (95% CI: 39-55%) among those with SMI (P < 0.001). All-cause mortality in the two groups was similar: 1.2% vs. 2.0% (P > 0.05). In multivariable analysis, the only baseline variable independently associated with breakage of continuous care was SMI (HR = 1.58, 95% CI: 1.06─2.33). Severe mental illness at ART initiation is associated with worse retention in HIV care in this urban Ugandan referral hospital. As ART is scaled up across sub-Saharan Africa, greater attention must be paid to the burden of mental illness and its impact on retention in care.

Lifetime depressive disorders and adherence to anti-retroviral therapy in HIV-infected Ugandan adults: A case-control study

BackgroundThere is limited information on the impact of lifetime depressive disorders on adherence to ART. AimWe examined the association between lifetime depressive disorders and adherence to anti-retroviral therapy (ART) among a rural clinic-based HIV positive population. We further explored whether this association was mediated by current depression and moderated by gender. MethodsTwo hundred HIV positive individuals who had<95% adherence and two hundred HIV positive individuals who had ≥95% adherence were screened for depression using the self-reporting questionnaire (SRQ-20) and evaluated with the Mini neuropsychiatric interview (MINI). Multivariate logistic regression was used to assess the association between lifetime depressive disorders and adherence to ART. The logistic regression model of Baron and Kenny was used to evaluate the mediating effect of current depression. Hierarchical binomial logistic regression was used to evaluate the moderating effect of gender. ResultsHIV positive individuals with lifetime depressive disorders had an increased risk of non-adherence to ART after controlling for education status, income, self-efficacy, perceived social support, cognitive impairment and current alcohol use disorders [AOR=1.68, 95%CI (1.02–2.79), p=0.04]. This association was stronger in females than males [AOR= 4.76, 95%CI (1.52–14.97), p=0.008]. LimitationsFindings cannot be generalized to ART naïve individuals or those using ART for less than six months. ConclusionLifetime depressive disorders are associated with increased risk of non-adherence to ART in rural women with HIV infection in southern Uganda. Detection and treatment of depression can potentially improve adherence with HIV treatment in this setting.

Response to comment on “Prevalence and factors associated with cryptococcal antigenemia among severely immunosuppressed HIV‐infected adults in Uganda (Oyella et al. 2012)”

We would like to thank you for the comments regarding our recent article: Cryptococcal antigenemia among severely immunosuppressed HIV-infected adults. In response to your comment: Sir, the recent report on ‘‘Prevalence and factors associated with cryptococcal antigenemia among severely immunosuppressed HIV-infected adults in Uganda’’ is very interesting. Oyella et al. concluded that ‘‘Independent predictors of positive serum cryptococcal antigenemia were CD4+ T cell counts of less than 50 cells/mm, low body mass index, neck pain, signs of meningeal irritation, and a recent diagnosis of HIV infection’’. This work is a cross sectional study, not a case-control study; hence, there might be some bias on assessment of risk factor. (Published: 2 August 2012) Citation: Oyella J et al. Journal of the International AIDS Society 2012, 15 :18003 http://www.jiasociety.org/index.php/jias/article/view/18003 | http://dx.doi.org/10.7448/IAS.15.2.18003

Comment on “Cryptococcal antigenemia among severely immunosuppressed HIV‐infected adults in Uganda (Oyella et al. 2012)”

The recent report on ‘‘Prevalence and factors associated with cryptococcal antigenemia among severely immunosuppressed HIV-infected adults in Uganda’’ is very interesting. Oyella et al. concluded that ‘‘Independent predictors of positive serum cryptococcal antigenemia were CD4+ T cell counts of less than 50 cells/mm, low body mass index, neck pain, signs of meningeal irritation, and a recent diagnosis of HIV infection’’. This work is a cross sectional study, not a case-control study; hence, there might be some bias on assessment of risk factor. (Published: 2 August 2012) Citation: Joob B and Wiwanitkit V. Journal of the International AIDS Society 2012, 15 :17977 http://www.jiasociety.org/index.php/jias/article/view/17977 | http://dx.doi.org/10.7448/IAS.15.2.17977

HIV-Infected Ugandan Adults Taking Antiretroviral Therapy With CD4 Counts &gt;200 Cells/ L Who Discontinue Cotrimoxazole Prophylaxis Have Increased Risk of Malaria and Diarrhea

Cotrimoxazole prophylaxis prolongs survival and prevents opportunistic infections, malaria, and diarrhea in persons infected with human immunodeficiency virus (HIV). Many countries recommend that individuals taking antiretroviral therapy (ART) discontinue cotrimoxazole when CD4 counts are >200 cells/μL. However, this practice has not been evaluated in sub-Saharan Africa. Patients in the Home-Based AIDS Care program in eastern Uganda initiated ART if they had a CD4 cell count ≤250 cells/μL or World Health Organization stage III or IV HIV disease. In the program's fourth year, patients with CD4 counts >200 cells/μL were randomly assigned, by household, to continue or discontinue cotrimoxazole. Consenting participants were followed for episodes of malaria and diarrhea. At randomization, 836 eligible patients had been receiving ART for a mean of 3.7 years, with a median CD4 count of 489 cells/μL; 94% had a viral load <400 copies/mL. Among those continuing (n = 452) vs discontinuing (n = 384) cotrimoxazole, 0.4 vs 12.2%, respectively, had at least 1 episode of malaria (P < .001), and 14% vs 25%, respectively, had at least 1 episode of diarrhea (P < .001). Compared to those remaining on cotrimoxazole, patients who discontinued had a relative risk of malaria of 32.5 (95% confidence interval [CI], 8.6-275.0; P < .001) and of diarrhea of 1.8 (95% CI, 1.3-2.4; P < .001). HIV-infected adults on ART with CD4 counts >200 cells/μL who live in a malaria-endemic area of sub-Saharan Africa and who abruptly discontinue cotrimoxazole prophylaxis have an increased incidence of malaria and diarrhea compared with those who continue prophylaxis. Clinical Trials Registration. NCT00119093.

Lopinavir/ritonavir significantly influences pharmacokinetic exposure of artemether/lumefantrine in HIV-infected Ugandan adults

BackgroundTreatment of HIV/malaria-coinfected patients with antiretroviral therapy (ART) and artemisinin-based combination therapy has potential for drug interactions. We investigated the pharmacokinetics of artemether, dihydroartemisinin and lumefantrine after administration of a single dose of 80/480 mg of artemether/lumefantrine to HIV-infected adults, taken with and without lopinavir/ritonavir.MethodsA two-arm parallel study of 13 HIV-infected ART-naive adults and 16 HIV-infected adults stable on 400/100 mg of lopinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors (ClinicalTrials.gov, NCT 00619944). Each participant received a single dose of 80/480 mg of artemether/lumefantrine under continuous cardiac function monitoring. Plasma concentrations of artemether, dihydroartemisinin and lumefantrine were measured.ResultsCo-administration of artemether/lumefantrine with lopinavir/ritonavir significantly reduced artemether maximum concentration (Cmax) and area under the concentration–time curve (AUC) [median (range): 112 (20–362) versus 56 (17–236) ng/mL, P = 0.03; and 264 (92–1129) versus 151 (38–606) ng · h/mL, P < 0.01]. Dihydroartemisinin Cmax and AUC were not affected [66 (10–111) versus 73 (31–224) ng/mL, P = 0.55; and 213 (68–343) versus 175 (118–262) ng · h/mL P = 0.27]. Lumefantrine Cmax and AUC increased during co-administration [2532 (1071–5957) versus 7097 (2396–9462) ng/mL, P < 0.01; and 41 119 (12 850–125 200) versus 199 678 (71 205–251 015) ng · h/mL, P < 0.01].ConclusionsCo-administration of artemether/lumefantrine with lopinavir/ritonavir significantly increases lumefantrine exposure, but decreases artemether exposure. Population pharmacokinetic and pharmacodynamic trials will be highly valuable in evaluating the clinical significance of this interaction and determining whether dosage modifications are indicated.

Prevalence and factors associated with cryptococcal antigenemia among severely immunosuppressed HIV‐infected adults in Uganda: a cross‐sectional study

BackgroundCryptococcal infection is a common opportunistic infection among severely immunosuppressed HIV patients and is associated with high mortality. Positive cryptococcal antigenemia is an independent predictor of cryptococcal meningitis and death in patients with severe immunosuppression. We evaluated the prevalence and factors associated with cryptococcal antigenemia among patients with CD4 counts of 100 cells/mm3 or less in Mulago Hospital, Kampala, Uganda. Screening of a targeted group of HIV patients may enable early detection of cryptococcal infection and intervention before initiating antiretroviral therapy. Factors associated with cryptococcal antigenemia may be used subsequently in resource-limited settings in screening for cryptococcal infection, and this data may also inform policy for HIV care.MethodsIn this cross-sectional study, HIV-infected patients aged 18 years and older with CD4 counts of up to 100 cells/mm3 were enrolled between December 2009 and March 2010. Data on socio-demographics, physical examinations and laboratory tests were collected. Factors associated with cryptococcal antigenemia were analyzed using multiple logistic regression.ResultsWe enrolled 367 participants and the median CD4 count was 23 (IQR 9-51) cells/mm3. Sixty-nine (19%) of the 367 participants had cryptococcal antigenemia. Twenty-four patients (6.5%) had cryptococcal meningitis on cerebrospinal fluid analysis and three had isolated cryptococcal antigenemia. Factors associated with cryptococcal antigenemia included: low body mass index of 15.4 kg/m2 or less (adjusted odds ratio, AOR = 0.5; 95% CI 0.3-1.0), a CD4+ T cell count of less than 50 cells/mm3 (AOR = 2.7; 95% CI1.2-6.1), neck pain (AOR = 2.3; 95% CI 1.2-4.6), recent diagnosis of HIV infection (AOR = 1.9; 95% CI 1.1-3.6), and meningeal signs (AOR = 7.9; 95% CI 2.9-22.1). However, at sub-analysis of asymptomatic patients, absence of neck pain (AOR = 0.5), photophobia (AOR = 0.5) and meningeal signs (AOR = 0.1) were protective against cryptococcal infection.ConclusionsCryptococcal antigenemia is common among severely immunosuppressed HIV patients in Mulago Hospital, Kampala, Uganda. Independent predictors of positive serum cryptococcal antigenemia were CD4+ T cell counts of less than 50 cells/mm, low body mass index, neck pain, signs of meningeal irritation, and a recent diagnosis of HIV infection. Routine screening of this category of patients may detect cryptococcosis, and hence provide an opportunity for early intervention. Absence of neck pain, photophobia and meningeal signs were protective against cryptococcal infection compared with symptomatic patients.

Cardiac Conduction Safety during Coadministration of Artemether-Lumefantrine and Lopinavir/Ritonavir in HIV-Infected Ugandan Adults

Background. We aimed to assess cardiac conduction safety of coadministration of the CYP3A4 inhibitor lopinavir/ritonavir (LPV/r) and the CYP3A4 substrate artemether-lumefantrine (AL) in HIV-positive Ugandans. Methods. Open-label safety study of HIV-positive adults administered single-dose AL (80/400 mg) alone or with LPV/r (400/100 mg). Cardiac function was monitored using continuous electrocardiograph (ECG). Results. Thirty-two patients were enrolled; 16 taking LPV/r -based ART and 16 ART naïve. All took single dose AL. No serious adverse events were observed. ECG parameters in milliseconds remained within normal limits. QTc measurements did not change significantly over 72 hours although were higher in LPV/r arm at 24 (424 versus 406; P = .02) and 72 hours (424 versus 408; P = .004) after AL intake. Conclusion. Coadministration of single dose of AL with LPV/r was safe; however, safety of six-dose AL regimen with LPV/r should be investigated.

Nevirapine/zidovudine/lamivudine has superior immunological and virological responses not reflected in clinical outcomes in a 48‐week randomized comparison with abacavir/zidovudine/lamivudine in HIV‐infected Ugandan adults with low CD4 cell counts

Triple nucleoside reverse transcriptase inhibitor regimens have advantages as first-line antiretroviral therapy (ART), avoiding hepatotoxicity and interactions with anti-tuberculosis therapy, and sparing two drug classes for second-line ART. Concerns exist about virological potency; efficacy has not been assessed in Africa. A safety trial comparing nevirapine with abacavir was conducted in two Ugandan Development of Antiretroviral Therapy in Africa (DART) centres: 600 symptomatic antiretroviral-naïve HIV-infected adults with CD4 counts <200 cells/microL were randomized to zidovudine/lamivudine plus abacavir or nevirapine (placebo-controlled to 24-week primary toxicity endpoint, and then open-label). Documented World Health Organization (WHO) stage 4 events were independently reviewed and plasma HIV-1 RNA assayed retrospectively. Exploratory efficacy analyses are intention-to-treat. The median pre-ART CD4 count was 99 cells/microL, and the median pre-ART viral load was 284 600 HIV-1 RNA copies/mL. A total of 563 participants (94%) completed 48 weeks of follow-up, 25 (4%) died and 12 (2%) were lost to follow-up. The randomized drug was substituted in 21 participants (7%) receiving abacavir vs. 34 (11%) receiving nevirapine (P=0.09). At 48 weeks, 62% of participants receiving abacavir vs. 77% of those receiving nevirapine had viral loads <50 copies/mL (P<0.001), and mean CD4 count increases from baseline were +147 vs. +173 cells/microL, respectively (P=0.006). Nine participants (3%) receiving abacavir vs. 16 (5%) receiving nevirapine died [hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.24-1.25; P=0.15]; 20 receiving abacavir vs. 32 receiving nevirapine developed new or recurrent WHO 4 events or died (HR=0.60; 95% CI 0.34-1.05; P=0.07) and 48 receiving abacavir vs. 68 receiving nevirapine developed new or recurrent WHO 3 or 4 events or died (HR=0.67; 95% CI 0.46-0.96; P=0.03). Seventy-one participants (24%) receiving abacavir experienced 91 grade 4 adverse events compared with 130 events in 109 participants (36%) on nevirapine (P<0.001). The clear virological/immunological superiority of nevirapine over abacavir was not reflected in clinical outcomes over 48 weeks. The inability of CD4 cell count/viral load to predict initial clinical treatment efficacy is unexplained and requires further evaluation.

Steady State Bioequivalence of Generic and Innovator Formulations of Stavudine, Lamivudine, and Nevirapine in HIV-Infected Ugandan Adults

BackgroundGeneric antiretroviral therapy is the mainstay of HIV treatment in resource-limited settings, yet there is little evidence confirming the bioequivalence of generic and brand name formulations. We compared the steady-state pharmacokinetics of lamivudine, stavudine and nevirapine in HIV-infected subjects who were receiving a generic formulation (Triomune®) or the corresponding brand formulations (Epivir®, Zerit®, and Viramune®).Methodology/Principal FindingsAn open-label, randomized, crossover study was carried out in 18 HIV-infected Ugandan subjects stabilized on Triomune-40. Subjects received lamivudine (150 mg), stavudine (40 mg), and nevirapine (200 mg) in either the generic or brand formulation twice a day for 30 days, before switching to the other formulation. At the end of each treatment period, blood samples were collected over 12 h for pharmacokinetic analysis. The main outcome measures were the mean AUC0–12h and Cmax. Bioequivalence was defined as a geometric mean ratio between the generic and brand name within the 90% confidence interval of 0.8–1.25. The geometric mean ratios and the 90% confidence intervals were: stavudine Cmax, 1.3 (0.99–1.71) and AUC0–12h, 1.1 (0.87–1.38); lamivudine Cmax, 0.8 (0.63–0.98) and AUC0–12h, 0.8 (0.65–0.99); and nevirapine Cmax, 1.1 (0.95–1.23) and AUC0–12h, 1.1 (0.95–1.31). The generic formulation was not statistically bioequivalent to the brand formulations during steady state, although exposures were comparable. A mixed random effects model identified about 50% intersubject variability in the pharmacokinetic parameters.Conclusions/Significant FindingsThese findings provide support for the use of Triomune in resource-limited settings, although identification of the sources of intersubject variability in these populations is critical.

Steady-state Pharmacokinetic Comparison of Generic and Branded Formulations of Lamivudine, Stavudine, and Nevirapine in HIV-infected Ugandan Adults

Steady-state Pharmacokinetic Comparison of Generic and Branded Formulations of Lamivudine, Stavudine, and Nevirapine in HIV-infected Ugandan Adults

HIV transmission risk behavior among HIV-infected adults in Uganda: results of a nationally representative survey

Evaluate factors associated with HIV transmission risk behavior among HIV-infected adults in Uganda. Cross-sectional and nationally representative study (2004-2005 Uganda HIV/AIDS Sero-Behavioral Survey) tested 18,525 adults (15-59 years old) for HIV and herpes simplex virus type 2 (HSV-2). Data were weighted to obtain nationally representative results. Sexual-risk behavior by HIV-infected individuals was defined as unprotected sex at last encounter. Using multivariate analysis, we identified factors associated with being sexually active, knowing HIV status, and using contraception and condoms. Of 1092 HIV-infected respondents, 64% were female (median age was 33 years), 84% had HSV-2, and 13% reported one lifetime partner (1% of men and 23% of women). Twenty-one percent of adults knew their HIV status and 9% knew their partners'. Seventy-seven percent were sexually active, of whom 27% reported condom use at last sex. Of last unprotected sexual encounters, 84% were with spouses and 13% with steady partners. Of cohabitating persons, 40% had an HIV-negative spouse. Those who knew their HIV status were three times more likely to use a condom at last sex encounter [adjusted odds ratio (AOR), 3.0; 95% confidence intervals (CI), 1.9-4.7] and those who knew their partners' HIV status were 2.3 times more likely to use condoms (AOR, 2.3; 95% CI, 1.2-4.3). A minority of HIV-infected adults in Uganda knew they had HIV infection; nearly half were in an HIV-discordant relationship, and few used condoms. Knowledge of HIV status, both one's own and one's partner's, was associated with increased condom use. Interventions to support HIV-infected persons and their partners to be tested are urgently needed.