Does provider-initiated counselling and testing (PITC) strengthen early diagnosis and treatment initiation? Results from an analysis of an urban cohort of HIV-positive patients in Lusaka, Zambia

Introduction: Building on earlier works demonstrating the effectiveness and acceptability of provider-initiated counselling and testing (PITC) services in integrated outpatient departments of urban primary healthcare clinics (PHCs), this study seeks to understand the relative utility of PITC services for identifying clients with early-stage HIV-related disease compared to traditional voluntary testing and counselling (VCT) services.We additionally seek to determine whether there are any significant differences in the clinical and demographic profile of PITC and VCT clients.\ud \ud Methods: Routinely collected, de-identified data were collated from two cohorts of HIV-positive patients referred for HIV treatment, either from PITC or VCT in seven urban-integrated PHCs. Univariate and multivariate analyses were conducted to compare the two cohorts across demographic and clinical characteristics at enrolment.\ud \ud Results: Forty-five per cent of clients diagnosed via PITC had CD4<200, and more than 70% (i.e. two thirds) had CD4<350 at enrolment, with significantly lower CD4 counts than that of VCT clients (p<0.001). PITC clients were more likely to be male (p<0.0005) and less likely to have secondary or tertiary education (p<0.0001). Among those who were initiated on antiretroviral therapy (ART), PITC clients had lower odds of initiating treatment within four weeks of enrolment into HIV care (adjusted odds ratio, or AOR: 0.86; 95% confidence interval, or CI: 0.750.99; p=0.035) and significantly lower odds of retention in care at six months (AOR: 0.84; CI: 0.770.99; p=0.004).\ud \ud Conclusions: In Lusaka, Zambia, large numbers of individuals with late-stage HIV are being incidentally diagnosed in outpatient settings. Our findings suggest that PITC in this setting does not facilitate more timely diagnosis and referral to care but rather act as a "safety net" for individuals who are unwilling or unable to seek testing independently. Further work is needed to document the way provision of clinic-based services can be strengthened and linked to community-based interventions and to address socio-cultural norms and socio-economic status that underpin healthcare-seeking behaviour

Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial.

BACKGROUND: HIV antiretroviral therapy (ART) is often managed without routine laboratory monitoring in Africa; however, the effect of this approach is unknown. This trial investigated whether routine toxicity and efficacy monitoring of HIV-infected patients receiving ART had an important long-term effect on clinical outcomes in Africa. METHODS: In this open, non-inferiority trial in three centres in Uganda and one in Zimbabwe, 3321 symptomatic, ART-naive, HIV-infected adults with CD4 counts less than 200 cells per microL starting ART were randomly assigned to laboratory and clinical monitoring (LCM; n=1659) or clinically driven monitoring (CDM; n=1662) by a computer-generated list. Haematology, biochemistry, and CD4-cell counts were done every 12 weeks. In the LCM group, results were available to clinicians; in the CDM group, results (apart from CD4-cell count) could be requested if clinically indicated and grade 4 toxicities were available. Participants switched to second-line ART after new or recurrent WHO stage 4 events in both groups, or CD4 count less than 100 cells per microL (LCM only). Co-primary endpoints were new WHO stage 4 HIV events or death, and serious adverse events. Non-inferiority was defined as the upper 95% confidence limit for the hazard ratio (HR) for new WHO stage 4 events or death being no greater than 1.18. Analyses were by intention to treat. This study is registered, number ISRCTN13968779. FINDINGS: Two participants assigned to CDM and three to LCM were excluded from analyses. 5-year survival was 87% (95% CI 85-88) in the CDM group and 90% (88-91) in the LCM group, and 122 (7%) and 112 (7%) participants, respectively, were lost to follow-up over median 4.9 years' follow-up. 459 (28%) participants receiving CDM versus 356 (21%) LCM had a new WHO stage 4 event or died (6.94 [95% CI 6.33-7.60] vs 5.24 [4.72-5.81] per 100 person-years; absolute difference 1.70 per 100 person-years [0.87-2.54]; HR 1.31 [1.14-1.51]; p=0.0001). Differences in disease progression occurred from the third year on ART, whereas higher rates of switch to second-line treatment occurred in LCM from the second year. 283 (17%) participants receiving CDM versus 260 (16%) LCM had a new serious adverse event (HR 1.12 [0.94-1.32]; p=0.19), with anaemia the most common (76 vs 61 cases). INTERPRETATION: ART can be delivered safely without routine laboratory monitoring for toxic effects, but differences in disease progression suggest a role for monitoring of CD4-cell count from the second year of ART to guide the switch to second-line treatment. FUNDING: UK Medical Research Council, the UK Department for International Development, the Rockefeller Foundation, GlaxoSmithKline, Gilead Sciences, Boehringer-Ingelheim, and Abbott Laboratories