Effect of follow-up counselling after HIV diagnosis through homebased HIV counselling and testing on linkage to HIV care in southwestern Uganda

Background: Home-based HIV counselling and testing (HBHCT) is highly acceptable and may be an effective strategy for HIV prevention and population-based test-and-treat programmes in sub-Saharan Africa (SSA). However, few data are available on linkage to care or on the effectiveness of strategies to increase linkage to care among HIVpositive persons identified through HBHCT in SSA. The aims of this PhD were to (i) systematically review the literature on linkage to care among HIV-positive adults diagnosed through HBHCT in SSA; and (ii) to conduct a cluster-randomised controlled trial to measure the effectiveness of a counselling intervention after HIV diagnosis through HBHCT in increasing linkage to care in rural Masaka district, Uganda. Methods: (i) Five databases (Medline, Embase, Global Health, Web of Science, and Africa-Wide information) were systematically searched for studies published between 1st January 2000 and 19th August 2016. Authors of studies for which some required information was missing were requested to provide additional data. (ii) For the trial, 28 rural communities were randomly allocated (1:1) to the intervention (HBHCT, referral, and brief home-based counselling sessions one and two months after HBHCT) or control group (HBHCT and referral only). HIV-positive adults (≥18 years) not yet in care were enrolled. Primary outcomes were linkage (registration with an HIV clinic) at 6 months after HBHCT, and time to linkage. Analyses were by intention-to-treat using random effects logistic regression and Cox regression with shared frailty. Results: (i) 19 eligible studies were identified; one had all the required data. Additional data were obtained for 13 studies; thus, 14 studies were included in the review. Linkage to care was generally lower (<33%) if HBHCT was followed by referral only, and higher (>80%) if some strategy was used to facilitate uptake of referral. Only one study was a randomised trial and most were susceptible to outcome ascertainment bias. (ii) In the trial, 551 individuals tested HIV-positive; 205 (37.2%) were already in care and thus ineligible. 302 (87.3% of those eligible) were enrolled (intervention, n=149). Retention was similar across trial arms (92% overall). Overall linkage to care was 42.1%. Counselling was associated with a 2.18-fold [95% confidence interval (CI)=1.26-3.78] increase in the odds of linkage. There was no evidence of a difference between arms in the rate of linkage in the first two months, but subsequently the rate of linkage was higher in the intervention arm (hazard ratio=4.87, 95% CI=1.79-13.27). Conclusion: Counselling substantially increases linkage to care among HIV-positive adults identified through HBHCT and can increase antiretroviral therapy coverage in SSA

Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda.

BACKGROUND: A six-dose antimalarial regimen of artemether-lumefantrine (A/L) may soon become one of the most widely used drug combination in Africa, despite possible constraints with adherence and poor absorption due to inadequate nutrition, and a lack of pharmacokinetic and effectiveness data. METHODS: Within a trial of supervised versus unsupervised A/L treatment in a stable Ugandan Plasmodium falciparum transmission setting, plasma lumefantrine concentrations were measured in a subset of patients on day 3 (C [lum]day3) and day 7 (C [lum]day7) post-inclusion. Predictors of lumefantrine concentrations were analysed to show how both C [lum]day7 and the weight-adjusted lumefantrine dose affect 28-day recrudescence and re-infection risks. The implications of these novel findings are discussed in terms of the emergence of lumefantrine-resistant strains in Africa. RESULTS: C [lum]day3 and C [lum]day7 distributions among 241 supervised and 238 unsupervised patients were positively skewed. Unsupervised treatment and decreasing weight-adjusted lumefantrine dose were negatively associated with C [lum]day3. Unsupervised treatment and decreasing age showed strong negative associations with C [lum]day7. Both models were poorly predictive (R-squared < 0.25). There were no recrudescences in either arm, but decreasing lumefantrine dose per Kg resulted in up to 13-fold higher adjusted risks of re-infection. Re-infections occurred only among patients with C [lum]day7 below 400 ng/mL (p < 0.001). CONCLUSION: Maintaining the present six-dose regimen and ensuring high adherence and intake are essential to maximize the public health benefits of this valuable drug combination

Sensitivity And Specificity Of Hiv Rapid Tests Used For Research And Voluntary Counselling And Testing

Background: HIV rapid tests (RT) are a quick and non-technically demanding means to perform HIV voluntary counselling and testing (VCT) but understanding their limitations is vital to delivering quality VCT. Objective: To determine the sensitivity and specificity of HIV rapid tests used for research and voluntary counselling and testing at four sites in East Africa. Design: Cross-sectional study. Setting: Masaka District, Uganda; a sugar plantation in Kakira, Uganda; Coastal Villages in the Kilifi District of Kenya; and the Urban slum of Kangemi located West of Nairobi, Kenya. Subjects: Six thousands two hundred and fifty five consenting volunteers were enrolled into the study, and 675 prevalent HIV infections were identified. Results: The RT sensitivity tended to be high for all assays at all sites (97.63-100%) with the exception of the Uni-Gold assay (90.24% in Kangemi, 96.58% in Kilifi). Twenty four RT results were recorded as ‘weak positives\', 22 (92%) of which were negative by ELISA. There was a high rate of RT false positives in Uganda (positive predictive values ranging from 45.70% to 86.62%). Conclusions: The sensitivity and specificity of the RT varied significantly across sites. The rate of RT misclassification in Uganda suggests that a multiple test algorithm may be preferable to a single test as screener for HIV VCT. East African Medical Journal Vol. 85 (10) 2008: pp. 500-50

Linkage to HIV care after home-based HIV counselling and testing in sub-Saharan Africa: A systematic review.

Home-based HIV counselling and testing (HBHCT) has the potential to increase HIV testing uptake in sub-Saharan Africa (SSA) but data on linkage to HIV care after HBHCT are scarce. We conducted a systematic review of linkage to care after HBHCT in SSA. Five databases were searched for studies published between 1(st) January 2000 and 19(th) August 2016 that reported on linkage to care among adults newly identified with HIV infection through HBHCT. Eligible studies were reviewed, assessed for risk of bias and findings summarised using the PRISMA guidelines. 14 studies from six countries met the eligibility criteria; 9 used specific strategies (point-of-care CD4 count testing, follow-up counselling, provision of transport funds to clinic, and counsellor facilitation of HIV clinic visit) in addition to routine referral to facilitate linkage to care. Time intervals for ascertaining linkage ranged from 1 week to 12 months post-HBHCT. Linkage ranged from 8.2% [95% confidence interval (CI), 6.8%-9.8%] to 99.1% (95% CI, 96.9%-99.9%). Linkage was generally lower (&lt;33%) if HBHCT was followed by referral only, and higher (&gt;80%) if additional strategies were used. Only 1 study assessed linkage by means of a randomised trial. 5 studies had data on cotrimoxazole (CTX) prophylaxis and 12 on ART eligibility and initiation. CTX uptake among those eligible ranged from 0% to 100%. The proportion of persons eligible for ART ranged from 16.5% (95% CI, 12.1-21.8) to 77.8% (95% CI, 40.0-97.2). ART initiation among those eligible ranged from 14.3% (95% CI, 0.36%-57.9%) to 94.9% (95% CI, 91.3%-97.4%). Additional linkage strategies, whilst seeming to increase linkage, were not associated with higher uptake of CTX and/or ART. Most of the studies were susceptible to risk of outcome ascertainment bias. A pooled analysis was not performed because of heterogeneity across studies with regard to design, setting, and the key variable definitions. Only few studies from SSA investigated linkage to care among adults newly diagnosed with HIV through HBHCT. Linkage was often low after routine referral but higher if additional interventions were used to facilitate it. The effectiveness of linkage strategies should be confirmed through randomised controlled trials. This article is protected by copyright. All rights reserved

Heterogeneity of HIV incidence : a comparative analysis between fishing communities and in a neighbouring rural general population, Uganda, and implications for HIV control

Objectives To describe HIV heterogeneity in rural Uganda using incidence data collected between January 2012 and December 2014 among fishing cohort (FC) and in an adjacent rural general population cohort (GPC). Methods In the FC, eligible HIV high-risk adults aged 18+ years were enrolled, followed and HIV tested every 3 months. Demographic and sexual behaviour data were also collected. The GPC, approximately 47 km away from the FC, was followed through annual surveys, and sociodemographic and behavioural data collected. A subset of GPC with comparable risk profiles to the FC was selected. We presented sociodemographic and risk profiles and also computed stratified HIV incidence. Cox regression was used to assess factors associated with HIV incidence. Results Overall HIV incidence was higher in the FC than in the ‘high-risk’ GPC, 6.04 and 0.56 per 100 person years at risk, respectively, with a rate ratio (RR) of 10.83 (95% CI 6.11 to 19.76). This was higher among those aged 18–24 years, unmarried and those with more than two sex partners in the past year, RR of 15.44, 22.99 and 19.29, respectively. In the FC, factors associated with high incidence in multivariate analysis were duration in the community and unprotected sex. The factors in the GPC were ethnicity, marital status and duration in the community. Conclusions We have observed a substantial heterogeneity in HIV incidence. The high incidence in fishing communities is contributing greatly to the overall HIV burden in Uganda, and thus urgent combination prevention efforts are needed towards national goal to reduce HIV epidemic

High Transmitter CD4+ T-Cell Count Shortly after the Time of Transmission in a Study of African Serodiscordant Couples.

© 2015 Karita et al.Background: 2013 WHO guidelines recommend starting ART at CD4+ T-cell counts ≤500 cells/μL. We present the T-cell counts from adult Africans with HIV shortly following transmission to their sexual partners. Methods: HIV-discordant couples in Zambia, Uganda and Rwanda were followed prospectively and received couples counseling and condoms. HIV uninfected partners were tested for HIV at least quarterly and HIV-infected partners received HIV care and referral for ART per national guidelines. Upon diagnosis of incident HIV infection in the previously HIV-uninfected partner, a blood sample was collected from both partners to measure CD4+ T-cells and perform viral linkage. The estimated date of infection (EDI) of the incident case was calculated based on testing history. EDI was unknown for suspected transmitting partners. Results: From 2006-2011, 4,705 HIV-discordant couples were enrolled in this cohort, and 443 cases of incident HIV infection were documented. Virus linkage analysis was performed in 374 transmission pairs, and 273 (73%) transmissions were linked genetically. CD4 counts in the transmitting partner were measured a median of 56 days after EDI (mean:90.5, min:10, max:396). The median CD4 count was 339 cells/μl (mean:386.4, min:15, max:1,434), and the proportion of partners with a CD4+ T-cell count above 500/μl was 25% (95% CI:21, 31). Conclusions: In our cohort of discordant couples, 73% of HIV transmissions occurred within the relationship, and the transmitter CD4+ T cell count shortly after the transmission event was frequently higher than the WHO 2013 ART-initiation guidelines. Copyright

Safety, Adherence and Acceptability of Intermittent Tenofovir/Emtricitabine as HIV Pre-Exposure Prophylaxis (PrEP) among HIV-Uninfected Ugandan Volunteers Living in HIV-Serodiscordant Relationships: A Randomized, Clinical Trial

Background: Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens. Design: Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment. Methods: Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS) and self-report. Sexual activity data were collected via daily short text message (SMS) and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT. Results: Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100) for daily PrEP regimen, 91% (IQR: 73-97) for fixed intermittent dosing and 45% (IQR: 20-63) for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen. Conclusions: Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing. Registration Clinicaltrials.gov number NCT0093134

Use of propensity score matching to create counterfactual group to assess potential HIV prevention interventions.

The design of HIV prevention trials in the context of effective HIV preventive methods is a challenge. Alternate designs, including using non-randomised 'observational control arms' have been proposed. We used HIV simulated vaccine efficacy trials (SiVETs) to show pitfalls that may arise from using such observational controls and suggest how to conduct the analysis in the face of the pitfalls. Two SiVETs were nested within previously established observational cohorts of fisherfolk (FF) and female sex workers (FSW) in Uganda. SiVET participants received a licensed Hepatitis B vaccine in a schedule (0, 1 and 6 months) similar to that for a possible HIV vaccine efficacy trial. All participants received HIV counselling and testing every quarter for one year to assess HIV incidence rate ratio (IRR) between SiVET and non-SiVET (observational data). Propensity scores, conditional on baseline characteristics were calculated for SiVET participation and matched between SiVET and non-SiVET in the period before and during the SiVET study. We compared IRR before and after propensity score matching (PSM). In total, 3989 participants were enrolled into observational cohorts prior to SiVET, (1575 FF prior to Jul 2012 and 2414 FSW prior to Aug 2014). SiVET enrolled 572 participants (Jul 2012 to Apr 2014 in FF and Aug 2014 to Apr 2017 in FSW), with 953 non-SiVET participants observed in the SiVET concurrent period and 2928 from the pre-SiVET period (before Jul 2012 in FF or before Apr 2014 in FSW). Imbalances in baseline characteristics were observed between SiVET and non-SiVET participants in both periods before PSM. Similarly, HIV incidence was lower in SiVET than non-SiVET; SiVET-concurrent period, IRR = 0.59, 95% CI 0.31-0.68, p = 0.033 and pre-SiVET period, IRR = 0.77, 95% CI 0.43-1.29, p = 0.161. After PSM, participants baseline characteristics were comparable and there were minimal differences in HIV incidence between SiVET and non-SiVET participants. The process of screening for eligibility for efficacy trial selects participants with baseline characteristics different from the source population, confounding any observed differences in HIV incidence. Propensity score matching can be a useful tool to adjust the imbalance in the measured participants' baseline characteristics creating a counterfactual group to estimate the effect of interventions on HIV incidence

COVID-19 Vaccine Acceptability Among Healthcare Facility Workers in Sierra Leone, the Democratic Republic of Congo and Uganda: A Multi-Centre Cross-Sectional Survey.

Objectives: This cross-sectional survey explored COVID-19 vaccine acceptability among public healthcare facility workers in Kambia (Sierra Leone), Goma (Democratic Republic of Congo) and Masaka (Uganda). Methods: Questionnaire-based interviews conducted between April-October 2021 explored participants' knowledge and perceptions of, and attitudes towards, the COVID-19 pandemic and COVID-19 vaccines, as well as COVID-19 vaccine acceptability (defined as uptake of ≥1 dose or intent to get vaccinated). Results: Whilst most (n = 444; 81.8%) of the 543 participants had one or more concerns about COVID-19 vaccines, 487 (89.7%) nonetheless perceived that they were important for pandemic control. Most participants from Kambia or Masaka either were vaccinated (n = 137/355; 38.6%) or intended to get vaccinated (n = 211/355; 59.4%) against COVID-19. In Goma, all 188 participants were unvaccinated; only 81 (43.1%) participants intended to get vaccinated, and this was associated with positive perceptions about COVID-19 vaccines. In Goma, the most common reasons for not wanting a COVID-19 vaccine were concerns that the vaccines were new (n = 75/107; 70.1%) and fear of side effects (n = 74/107; 69.2%). Conclusion: Reported COVID-19 vaccine acceptability was high among healthcare facility workers in Kambia and Masaka. The lower vaccine acceptability in Goma may highlight the importance of social mobilisation and accurate, accessible information that addresses specific concerns