Provision of cervical cancer services for women living with HIV, Uganda.

Objective: To describe the scale-up of cervical cancer screening and treatment for women living with human immunodeficiency virus (HIV), aged 25-49 years in Uganda, and to analyse the programme data. Methods: The health ministry targeted existing HIV clinics in a 2-year scale-up of cervical cancer screening services from October 2020. In preparation, we trained health workers to assess women attending HIV clinics for screening eligibility, provided either by human papillomavirus (HPV) testing and/or visual inspection with acetic acid. Clinic staff treated women with precancerous cervical lesions with thermocoagulation or referred women with suspected cancer to external services. We analysed data reported every 6 months for the number of clinics offering screening, screening uptake, the number of positive diagnoses and the number of women who received treatment. Findings: The number of HIV clinics offering cervical cancer screening services increased from 11, before the programme launch, to 1571. During the programme, screening uptake increased from 5.0% (6506/130 293) to 107.3% (151 872/141 527) of targets. The cumulative proportion of positive diagnoses was 5.9% (23 970/407 323) overall, but was much lower for screening offering visual inspection only compared with clinics offering HPV testing. Although the proportion of women receiving treatment if positive increased from 12.8% (53/413) to 84.3% (8087/9592), the World Health Organization target of 90% was not reached. Conclusion: We demonstrated marked increases, potentially replicable by other countries, in screening and treatment. These increases could be improved further by expanding HPV testing and same-day treatment of precancerous lesions.

Tuberculosis Preventive Therapy among Persons Living with HIV, Uganda, 2016-2022.

During October 2016-March 2022, Uganda increased tuberculosis (TB) preventive therapy coverage among persons living with HIV from 0.6% to 88.8%. TB notification rates increased from 881.1 to 972.5 per 100,000 persons living with HIV. Timely TB screening, diagnosis, and earlier treatment should remain high priorities for TB/HIV prevention programming.

Decreases in self-reported alcohol consumption following HIV counseling and testing at Mulago Hospital, Kampala, Uganda.

BACKGROUND: Alcohol use has a detrimental impact on the HIV epidemic, especially in sub-Saharan Africa. HIV counseling and testing (HCT) may provide a contact opportunity to intervene with hazardous alcohol use; however, little is known about how alcohol consumption changes following HCT. METHODS: We utilized data from 2056 participants of a randomized controlled trial comparing two methods of HCT and subsequent linkage to HIV care conducted at Mulago Hospital in Kampala, Uganda. Those who had not previously tested positive for HIV and whose last HIV test was at least one year in the past were eligible. Participants were asked at baseline when they last consumed alcohol, and prior three month alcohol consumption was measured using the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) at baseline and quarterly for one year. Hazardous alcohol consumption was defined as scoring ≥3 or ≥4 for women and men, respectively. We examined correlates of alcohol use at baseline, and of hazardous and non-hazardous drinking during the year of follow-up using multinomial logistic regression, clustered at the participant level to account for repeated measurements. RESULTS: Prior to HCT, 30% were current drinkers (prior three months), 27% were past drinkers (>3 months ago), and 44% were lifetime abstainers. One-third (35%) of the current drinkers met criteria for hazardous drinking. Hazardous and non-hazardous self-reported alcohol consumption declined after HCT, with 16% of baseline current drinkers reporting hazardous alcohol use 3 months after HCT. Independent predictors (p < 0.05) of continuing non-hazardous and hazardous alcohol consumption after HCT were sex (male), alcohol consumption prior to HCT (hazardous), and HIV status (negative). Among those with HIV, non-hazardous drinking was less likely among those taking antiretroviral therapy (ART). CONCLUSIONS: HCT may be an opportune time to intervene with alcohol consumption. Those with HIV experienced greater declines in alcohol consumption after HCT, and non-hazardous drinking decreased for those with HIV initiating ART. HCT and ART initiation may be ideal times to intervene with alcohol consumption. Screening and brief intervention (SBI) to reduce alcohol consumption should be considered for HCT and HIV treatment venues.

Abbreviated HIV counselling and testing and enhanced referral to care in Uganda: a factorial randomised controlled trial.

BACKGROUND: HIV counselling and testing and linkage to care are crucial for successful HIV prevention and treatment. Abbreviated counselling could save time; however, its effect on HIV risk is uncertain and methods to improve linkage to care have not been studied. METHODS: We did this factorial randomised controlled study at Mulago Hospital, Uganda. Participants were randomly assigned to abbreviated or traditional HIV counselling and testing; HIV-infected patients were randomly assigned to enhanced linkage to care or standard linkage to care. All study personnel except counsellors and the data officer were masked to study group assignment. Participants had structured interviews, given once every 3 months. We compared sexual risk behaviour by counselling strategy with a 6·5% non-inferiority margin. We used Cox proportional hazards analyses to compare HIV outcomes by linkage to care over 1 year and tested for interaction by sex. This trial is registered with ClinicalTrials.gov (NCT00648232). FINDINGS: We enrolled 3415 participants; 1707 assigned to abbreviated counselling versus 1708 assigned to traditional. Unprotected sex with an HIV discordant or status unknown partner was similar in each group (232/823 [27·9%] vs 251/890 [28·2%], difference -0·3%, one-sided 95% CI 3·2). Loss to follow-up was lower for traditional counselling than for abbreviated counselling (adjusted hazard ratio [HR] 0·61, 95% CI 0·44-0·83). 1003 HIV-positive participants were assigned to enhanced linkage (n=504) or standard linkage to care (n=499). Linkage to care did not have a significant effect on mortality or receipt of co-trimoxazole. Time to treatment in men with CD4 cell counts of 250 cells per µL or fewer was lower for enhanced linkage versus standard linkage (adjusted HR 0·60, 95% CI 0·41-0·87) and time to HIV care was decreased among women (0·80, 0·66-0·96). INTERPRETATION: Abbreviated HIV counselling and testing did not adversely affect risk behaviour. Linkage to care interventions might decrease time to enrolment in HIV care and antiretroviral treatment and thus might affect secondary HIV transmission and improve treatment outcomes. FUNDING: US National Institute of Mental Health.

Plasma drug level validates self-reported adherence but predicts limited specificity for nonadherence to antiretroviral therapy.

Introduction. Adherence to antiretroviral therapy (ART) in low-income countries is mainly assessed by self-reported adherence (S-RA) without drug level determination. Nonadherence is an important factor in the emergence of resistance to ART, presenting a need for drug level determination. Objective. We set out to establish the relationship between plasma stavudine levels and S-RA and validate S-RA against the actual plasma drug concentrations. Methods. A cross-sectional investigation involving 234 patients in Uganda. Stavudine plasma levels were determined using high-performance liquid chromatography. We compared categories of plasma levels of stavudine with S-RA using multivariable logistic regression models. Results. Overall, 194/234 patients had S-RA ≥ 95% (good adherence) and 166/234 had stavudine plasma concentrations ≥ 36 nmol/L (therapeuticconcentration). Patients with good S-RA were eight times more likely to have stavudine levels within therapeutic concentration (Adjusted Odds Ratio: 7.7, 95% Confidence Interval: 3.5-7.0). However, of the 194 patients with good S-RA, 21.7% had below therapeutic concentrations. S-RA had high sensitivity for adherence (91.6%), but limited specificity for intrinsic poor adherence (38.2%). Conclusions. S-RA is a good tool for assessing adherence, but has low specificity in detecting nonadherence, which has implications for emergence of resistance.

Potential for false positive HIV test results with the serial rapid HIV testing algorithm.

BACKGROUND: Rapid HIV tests provide same-day results and are widely used in HIV testing programs in areas with limited personnel and laboratory infrastructure. The Uganda Ministry of Health currently recommends the serial rapid testing algorithm with Determine, STAT-PAK, and Uni-Gold for diagnosis of HIV infection. Using this algorithm, individuals who test positive on Determine, negative to STAT-PAK and positive to Uni-Gold are reported as HIV positive. We conducted further testing on this subgroup of samples using qualitative DNA PCR to assess the potential for false positive tests in this situation. RESULTS: Of the 3388 individuals who were tested, 984 were HIV positive on two consecutive tests, and 29 were considered positive by a tiebreaker (positive on Determine, negative on STAT-PAK, and positive on Uni-Gold). However, when the 29 samples were further tested using qualitative DNA PCR, 14 (48.2%) were HIV negative. CONCLUSION: Although this study was not primarily designed to assess the validity of rapid HIV tests and thus only a subset of the samples were retested, the findings show a potential for false positive HIV results in the subset of individuals who test positive when a tiebreaker test is used in serial testing. These findings highlight a need for confirmatory testing for this category of individuals.

Missed opportunities for HIV testing and late-stage diagnosis among HIV-infected patients in Uganda.

BACKGROUND: Late diagnosis of HIV infection is a major challenge to the scale-up of HIV prevention and treatment. In 2005 Uganda adopted provider-initiated HIV testing in the health care setting to ensure earlier HIV diagnosis and linkage to care. We provided HIV testing to patients at Mulago hospital in Uganda, and performed CD4 tests to assess disease stage at diagnosis. METHODS: Patients who had never tested for HIV or tested negative over one year prior to recruitment were enrolled between May 2008 and March 2010. Participants who tested HIV positive had a blood draw for CD4. Late HIV diagnosis was defined as CD4≤250 cells/mm. Predictors of late HIV diagnosis were analyzed using multi-variable logistic regression. RESULTS: Of 1966 participants, 616 (31.3%) were HIV infected; 47.6% of these (291) had CD4 counts ≤250. Overall, 66.7% (408) of the HIV infected participants had never received care in a medical clinic. Receiving care in a non-medical setting (home, traditional healer and drug stores) had a threefold increase in the odds of late diagnosis (OR = 3.2; 95%CI: 2.1-4.9) compared to receiving no health care. CONCLUSIONS: Late HIV diagnosis remains prevalent five years after introducing provider-initiated HIV testing in Uganda. Many individuals diagnosed with advanced HIV did not have prior exposure to medical clinics and could not have benefitted from the expansion of provider initiated HIV testing within health facilities. In addition to provider-initiated testing, approaches that reach individuals using non-hospital based encounters should be expanded to ensure early HIV diagnosis.

Validation of World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy and clinical predictors of low CD4 cell count in Uganda.

INTRODUCTION: The WHO clinical guidelines for HIV/AIDS are widely used in resource limited settings to represent the gold standard of CD4 counts for antiviral therapy initiation. The utility of the WHO-defined stage 1 and 2 clinical factors used in WHO HIV/AIDS clinical staging in predicting low CD4 cell count has not been established in Uganda. Although the WHO staging has shown low sensitivity for predicting CD4<200 cells/mm(3), it has not been evaluated at for CD4 cut-offs of <250 cells/mm(3) or <350 cells/mm(3). OBJECTIVE: To validate the World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy in a low-resource setting and to determine the clinical predictors of low CD4 cell count in Uganda. RESULTS: Data was collected on 395 participants from the Joint Clinical Research Centre, of whom 242 (61.3%) were classified as in stages 1 and 2 and 262 (68%) were females. Participants had a mean age of 36.8 years (SD 8.5). We found a significant inverse correlation between the CD4 lymphocyte count and WHO clinical stages. The sensitivity the WHO clinical staging at CD4 cell count of 250 cells/mm(3) and 350 cells/mm(3) was 53.5% and 49.1% respectively. Angular cheilitis, papular pruritic eruptions and recurrent upper respiratory tract infections were found to be significant predictors of low CD4 cell count among participants in WHO stage 1 and 2. CONCLUSION: The WHO HIV/AIDS clinical staging guidelines have a low sensitivity and about half of the participants in stages 1 and 2 would be eligible for ART initiation if they had been tested for CD4 count. Angular cheilitis and papular pruritic eruptions and recurrent upper respiratory tract infections may be used, in addition to the WHO staging, to improve sensitivity in the interim, as access to CD4 machines increases in Uganda.