Guidelines For Initiation Of Antiretroviral Therapy Research Articles

Effectiveness of early initiation of antiretroviral therapy in adults with HIV associated tuberculosis in Lesotho in 2012

Background:Lesotho has a huge burden of human immunodeficiency virus associated tuberculosis (HIV-TB). In this study we compared the effectiveness of early versus late commencement of antiretroviral therapy (ART) in adults living with HIV-TB in Lesotho.Methods: Three out of 17 hospitals were randomly selected and data extracted from the hospitals’ tuberculosis (TB) treatment registers for 247 adults living with HIV-TB who completed TB therapy during the first quarter of 2012.Results: Eighty (32%) commenced ART early (4 weeks), 100 (41%) were started late (≥4 weeks) and 67 (27%) received no ART. Both early and late ART initiators were more likely to have a successful TB outcome (Adjusted Odds Ratio (AOR) 10.1, 95% CI: 3.7 - 27.5 and AOR 8.4, 95% CI: 3.4 - 20.6, respectively) relative to the group who had no ART (p 0.001).Conclusions: Effective treatment exists for managing HIV-TB simultaneously. The guidelines for initiation of ART in adult HIV-TB in Lesotho have not been fully implemented, but those who commenced ART had significant clinical benefits. Health departments must address the challenges encountered in treating HIV-TB simultaneously to ensure those co-infected receive optimal care.

Effectiveness of early initiation of antiretroviral therapy in adults with HIV associated tuberculosis in Lesotho in 2012

Background: Lesotho has a huge burden of human immunodeficiency virus associated tuberculosis (HIV-TB). In this study we compared the effectiveness of early versus late commencement of antiretroviral therapy (ART) in adults living with HIV-TB in Lesotho.Methods: Three out of 17 hospitals were randomly selected and data extracted from the hospitals’ tuberculosis (TB) treatment registers for 247 adults living with HIV-TB who completed TB therapy during the first quarter of 2012.Results: Eighty (32%) commenced ART early (<4 weeks), 100 (41%) were started late (≥4 weeks) and 67 (27%) received no ART. Both early and late ART initiators were more likely to have a successful TB outcome (Adjusted Odds Ratio (AOR) 10.1, 95% CI: 3.7 - 27.5 and AOR 8.4, 95% CI: 3.4 - 20.6, respectively) relative to the group who had no ART (p < 0.001).Conclusions: Effective treatment exists for managing HIV-TB simultaneously. The guidelines for initiation of ART in adult HIV-TB in Lesotho have not been fully implemented, but those w...

Antiretroviral Treatment Scale-up Among Persons Living With HIV in Kenya

In 2007, 29% of HIV-infected Kenyans in need of antiretroviral therapy (ART), based on an immunologic criterion of CD4 ≤350 cells per microliter, were receiving ART. Since then, substantial treatment scale-up has occurred in the country. We analyzed data from the second Kenya AIDS Indicator Survey (KAIS 2012) to assess progress of treatment scale-up in Kenya. KAIS 2012 was a nationally representative survey of persons aged 18 months to 64 years that collected information on HIV status, care, and treatment. ART eligibility was defined based on 2 standards: (1) 2011 Kenya eligibility criteria for ART initiation: CD4 ≤350 cells per microliter or co-infection with active tuberculosis and (2) 2013 World Health Organization (WHO) eligibility criteria for ART initiation: CD4 ≤500 cells per microliter, co-infection with active tuberculosis, currently pregnant or breastfeeding, and infected partners in serodiscordant relationships. Blood specimens were tested for HIV antibodies and HIV-positive specimens tested for CD4 cell counts. Among 13,720 adults and adolescents aged 15-64 years, 11,626 provided a blood sample, and 648 were HIV infected. Overall, 58.8% [95% confidence interval (CI): 52.0 to 65.5) were eligible for treatment using the 2011 Kenya eligibility criteria and 77.4% (95% CI: 72.4 to 82.4) using the 2013 WHO eligibility criteria. Coverage of ART was 60.5% (95% CI: 50.8 to 70.2) using the 2011 Kenya eligibility criteria and 45.9% (95% CI: 37.7 to 54.2) using the 2013 WHO eligibility criteria. ART coverage has increased from 29% in 2007 to 61% in 2012. If Kenya adopts the 2013 WHO guidelines for ART initiation, need for ART increases by an additional 19 percentage points and current coverage decreases by an additional 15 percentage points, representing an additional 214,000 persons who will need to be reached.

Correction: Is Clinical Practice Concordant with the Changes in Guidelines for Antiretroviral Therapy Initiation during Primary and Chronic HIV-1 Infection? The ANRS PRIMO and COPANA Cohorts

Correction: Is Clinical Practice Concordant with the Changes in Guidelines for Antiretroviral Therapy Initiation during Primary and Chronic HIV-1 Infection? The ANRS PRIMO and COPANA Cohorts

Is clinical practice concordant with the changes in guidelines for antiretroviral therapy initiation during primary and chronic HIV-1 infection? The ANRS PRIMO and COPANA cohorts.

ObjectiveGuidelines for initiating HIV treatment are regularly revised. We explored how physicians in France have applied these evolving guidelines for ART initiation over the last decade in two different situations: chronic (CHI) and primary HIV-1 infection (PHI), since specific recommendations for PHI are also provided in France.MethodsData came from the ANRS PRIMO (1267 patients enrolled during PHI in 1996–2010) and COPANA (800 subjects enrolled at HIV diagnosis in 2004–2008) cohorts. We defined as guidelines-inconsistent during PHI and CHI, patients meeting criteria for ART initiation and not treated in the following month and during the next 6 months, respectively.ResultsART initiation during PHI dramatically decreased from 91% of patients in 1996–99 to 22% in 2007 and increased to 60% in 2010, following changes in recommendations. In 2007, however, after the CD4 count threshold was raised to 350 cells/mm3 in 2006, only 55% of the patients with CD4≤350 were treated and 66% in 2008. During CHI, ART was more frequently initiated in patients who met the criteria at entry (96%) than during follow-up: 83% when recommendation to treat was 200 and 73% when it was 350 cells/mm3. Independent risk factors for not being treated during CHI despite meeting the criteria were lower viral load, lower educational level, and poorer living conditions.ConclusionHIV ART initiation guidelines are largely followed by practitioners in France. What can still be improved, however, is time to treat when CD4 cell counts reach the threshold to treat. Risk factors for lack of timely treatment highlight the need to understand better how patients’ living conditions and physicians’ perceptions influence the decision to initiate treatment.

Impact of generic antiretroviral therapy (ART) and free ART programs on time to initiation of ART at a tertiary HIV care center in Chennai, India

Antiretroviral therapy (ART) access in the developing world has improved, but whether increased access has translated to more rapid treatment initiation among those who need it is unknown. We characterize time to ART initiation across three eras of ART availability in Chennai, India (1996–1999: pregeneric; 2000–2003: generic; 2004–2007: free rollout). Between 1996 and 2007, 11,171 patients registered for care at the YR Gaitonde Centre for AIDS Research and Education (YRGCARE), a tertiary HIV referral center in southern India. Of these, 5726 patients became eligible for ART during this period as per Indian guidelines for initiation of ART. Generalized gamma survival models were used to estimate relative times (RT) to ART initiation by calendar periods of eligibility. Time to initiation of ART among patients in Chennai, India was also compared to an HIV clinical cohort in Baltimore, USA. Median age of the YRGCARE patients was 34 years; 77% were male. The median CD4 at presentation was 140 cells/µl. After adjustment for demographics, CD4 and WHO stage, persons in the pregeneric era took 3.25 times longer (95% confidence interval [CI]: 2.53–4.17) to initiate ART versus the generic era and persons in the free rollout era initiated ART more rapidly than the generic era (RT: 0.73; 95% CI: 0.63–0.83). Adjusting for differences across centers, patients at YRGCARE took longer than patients in the Johns Hopkins Clinical Cohort (JHCC) to initiate ART in the pregeneric era (RT: 4.90; 95% CI: 3.37–7.13) but in the free rollout era, YRGCARE patients took only about a quarter of the time (RT: 0.31; 95% CI: 0.22–0.44). These data demonstrate the benefits of generic ART and government rollouts on time to initiation of ART in one developing country setting and suggests that access to ART may be comparable to developed country settings.

Implications of adopting new WHO guidelines for antiretroviral therapy initiation in Ethiopia

To assess the implications of implementing the World Health Organization (WHO) 2010 guidelines for antiretroviral therapy (ART) initiation in adults and adolescents with human immunodeficiency virus (HIV) infection, which recommend initiating ART at a CD4+ T lymphocyte (CD4+) threshold of ≤ 350 cells/mm(3) instead of ≤ 200 cells/mm(3), which was the earlier threshold. Between April and May 2010, CD4+ test results were collected for all HIV-infected patients recorded in the pre-ART and ART registers of 19 high-patient-load health centres in Addis Ababa, Ethiopia, and the regions of Amhara, Oromia, SNNPR (Southern Nations, Nationalities and People's Region) and Tigray. At 12 centres patient records were independently reviewed to assess data accuracy. To estimate the total number of patients who would need ART at health centres if Ethiopia adopted the new WHO guidelines, the number of patients needing ART based on current guidelines were added to the number of asymptomatic patients enrolled in pre-ART with a CD4+ count > 200 but ≤ 350 cells/mm(3) Adoption of the new WHO guidelines would increase the total number of patients on ART in the 19 health centres in Ethiopia by about 30%: from 3583 to 4640. The shift in the CD4+ threshold for ART initiation will substantially increase the demand for ART in Ethiopia. Since under the current systems only 60% of Ethiopia's patients in need of ART are receiving the medications, scaling up ART programmes to accommodate the increased demand for drugs will not be possible unless government funding and support increase concurrently.

Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis

High plasma HIV-1 RNA concentrations are associated with increased risk of HIV-1 transmission. Initiation of antiretroviral therapy (ART) reduces plasma HIV-1 concentrations. We aimed to assess the effect of ART use by patients infected with HIV-1 on risk of transmission to their uninfected partners. Participants in our prospective cohort analysis were from a randomised placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus type 2, and their HIV-1 seronegative partners. At enrolment, HIV-1 infected participants had CD4 counts of 250 cells per microL or greater and did not meet national guidelines for ART initiation; during 24 months of follow-up, CD4 counts were measured every 6 months and ART was initiated in accordance with national guidelines. Uninfected partners were tested for HIV-1 every 3 months. The primary outcome was genetically-linked HIV-1 transmission within the study partnership. We assessed rates of HIV-1 transmission by ART status of infected participants. 3381 couples were eligible for analysis. 349 (10%) participants with HIV-1 initiated ART during the study, at a median CD4 cell count of 198 (IQR 161-265) cells per microL. Only one of 103 genetically-linked HIV-1 transmissions was from an infected participant who had started ART, corresponding to transmission rates of 0.37 (95% CI 0.09-2.04) per 100 person-years in those who had initiated treatment and 2.24 (1.84-2.72) per 100 person-years in those who had not-a 92% reduction (adjusted incidence rate ratio 0.08, 95% CI 0.00-0.57, p=0.004). In participants not on ART, the highest HIV-1 transmission rate (8.79 per 100 person-years) was from those with CD4 cell counts lower than 200 cells per microL. In couples in whom the untreated HIV-1 infected partner had a CD4 cell count greater than 200 cells per microL, 66 (70%) of 94 transmissions occurred when plasma HIV-1 concentrations exceeded 50 000 copies per mL. Low CD4 cell counts and high plasma HIV-1 concentrations might guide use of ART to achieve an HIV-1 prevention benefit. Provision of ART to HIV-1 infected patients could be an effective strategy to achieve population-level reductions in HIV-1 transmission. Bill & Melinda Gates Foundation; US National Institutes of Health.

Toward genetic rationalization of antiretroviral therapy for HIV

Daar et al. have extended the observations of Barbour et al. on the correlation between disease progression and standardized HIV polymerase activity in vitro. Polymerase thus joins accessory genes (nef rev tat vif vpr vpu reviewed in) as well as tropism-determining envelope as a potentially useful prognostic marker for disease progression and treatment initiation albeit one that must be functionally assayed (like envelope tropism) rather than genetically screened. For treatment-experienced patients reverse transcriptase and protease are already widely monitored for mutations predictive of drug resistance (reviewed). Thus Daar et al. provide one more step toward the individualization of antiretroviral therapy (ART) by fine tuning decisions made in the context of CD4 cell counts viremia and drug resistance. (excerpt)