HIV This Week

Seyler and colleagues’ objectives were to analyse the association between the presence of resistance mutations and treatment outcomes. The impact of HIV-1 drug resistance mutations in African adults on HAART (highly active antiretroviral treatment) has so far never been reported. In 2004 in Abidjan, Cote d’Ivoire, 106 adults on HAART had plasma viral load measurements. Patients with detectable viral loads had resistance genotypic tests. Patients were followed until 2006. Main outcomes were serious morbidity and immunological failure (CD4 cell count < 200 cells/mul). The results showed that at study entry, the median previous time on HAART was 37 months and the median CD4 cell count was 266 cells/mul; 58% of patients had undetectable viral loads, 20% had detectable viral loads with no major resistance mutations, and 22% had detectable viral loads with one or more major mutations. The median change in CD4 cell count between study entry and study termination was +129 cells/mul in patients with undetectable viral loads, +51 cells/mul in those with detectable viral loads with no mutations and +3 cells/mul in those with detectable viral loads with resistance mutations. Compared with patients with undetectable viral loads, those with detectable viral loads with resistance mutations had adjusted hazard ratios of immunological failure of 4.32 (95%CI 1.38-13.57, P = 0.01). One patient died. The 18-month probability of remaining free of morbidity was 0.79 in patients with undetectable viral loads and 0.69 in those with resistance mutations (P = 0.19). The authors conclude that in this setting with restricted access to second-line HAART, patients with major resistance mutations had higher rates of immunological failure, but most maintained stable CD4 cell counts and stayed alive for at least 20 months.

Editors’ note: Detectable viral loads are more likely in any setting to be associated with an increased likelihood of morbidity and immunological failure over time. This Ivory Coast study of 106 patients who had already been on antiretroviral therapy for a median of 3 years likely had too few subjects and too short a period of follow-up to demonstrate differences in morbidity among those who had detectable viral loads versus those that didn’t, let alone to demonstrate differences by whether they had resistance mutations or not. In any case, drug resistance testing in the absence of second line therapy would put the cart before the horse. Bringing down the cost of second line drugs to make them more accessible is a clear priority.

Stangl and colleagues examined trends and predictors of quality of life (QOL) over 12 months among a prospective cohort of 947 HIV-1-infected adults initiating highly active antiretroviral therapy (HAART) between May 2003 and May 2004 in rural Uganda.  Participants provided clinical, demographic and psychosocial data at baseline and every three months thereafter. Outcome measures included physical and mental health summary scores based on the Medical Outcomes Study-HIV Health Survey (MOS-HIV). Generalised estimating equations were used to assess magnitude of change in summary scores and factors associated with QOL. Of 710 women and 237 men enrolled, the mean age was 38.7 years and mean baseline CD4 cell count was 124.1 cells/microL. At enrolment, physical and mental health summary scores were 39.2 and 40, respectively. By 12 months of HAART, scores increased by 11.2 points (p <0.001) and 7.4 points (p <0.001), respectively. For both scores, most gains were achieved by the third month of therapy. While several clinical, psychosocial and socio-demographic factors predicted quality of life at HAART initiation, financial dependence on others was the only remaining predictor after controlling for time on HAART. Interventions to enhance the economic and employment opportunities of patients taking HAART in rural Africa may help maximise gains in QOL.

Editors’ note: As people’s quality of life improves after initiating antiretroviral treatment, their capacity to return to work and contribute to family and community life increases. Treatment programmes should help patients anticipate this shift and plan for reintegration into productive activities – for their own and the community’s benefit.

The ability of WHO clinical staging to predict CD4 cell counts of 200 cells/mul or less was evaluated among 1221 patients screened for antiretroviral therapy (ART). Sensitivity was 51% and specificity was 88%. The positive predictive value was 64% and the negative predictive value was 81%. Clinical criteria missed half the patients with CD4 cell counts of 200 cells/mul or less, highlighting the importance of CD4 cell measurements for the scale-up of ART provision in resource-limited settings.

Editors’ note: People with symptoms and signs indicative of HIV disease who test HIV-positive are eligible for antiretroviral treatment in the absence of CD4 count testing. This study highlights the importance of CD4 count testing for those who are asymptomatic and HIV-positive. Waiting for them to develop disease misses an important window of opportunity to improve their long-term survival.

Mehta and colleagues examined the prevalence and prognostic value of early responses to highly active antiretroviral therapy (HAART) among community-based injection drug users (IDUs) in Baltimore. Virologic (HIV RNA <1000 copies/ml) and immunologic (CD4 >500 cells/ul or increase of 50 cells/ul from the pre-HAART level) responses were examined in the 1st year of HAART initiation. Cox regression was used to examine the effect of early response on progression to new AIDS diagnosis or AIDS-related death. Among 258 HAART initiators, 75(29%) had no response, 53(21%) had a virologic response only, 38(15%) had an immunologic response only and 92(36%) had a combined immunologic and virologic response in the first year of therapy. Poorer responses were observed in those who were older, had been recently incarcerated, reported injecting drugs, had not had a recent outpatient visit and had some treatment interruption within the 1st year of HAART. In multiple Cox regression analysis, the risk of progression was lower in those with combined virologic and immunologic response than in non-responders, (relative hazard [RH], 0.32; 95% confidence interval [CI], 0.17-0.60). Those with discordant responses had reduced risk of progression compared to non-responders but experienced faster progression than those with a combined response, although none of these differences was statistically significant. Early discordant and non response to HAART was common, often occurred in the setting of injection drug use and treatment interruption and was associated with poorer survival. Interventions to reduce treatment interruptions and to provide continuity of HIV care during incarceration among IDUs are needed to improve responses and subsequent survival.

Editors’ note: Transitions between the community and the prison and then between the prison and the community are critical for ensuring that people taking antiretroviral medications who are being incarcerated or who are being released continue to take their medications without interruption. Public health and correctional authorities should examine the circumstances around incarceration and release in order to design interventions aimed at ensuring treatment continuity – for HIV and for other chronic conditions.

This study assesses AIDS survival time per AIDS-case definition and exposure category in Sao Paulo State, Brazil during the periods 1992 to 1995 and 1998 to 2001. Kilsztajn andd colleagues employed case-fatality rate per AIDS case, Cox proportional hazards analysis, and Kaplan-Meier survival time. Their results showed that the case-fatality rate per AIDS case in 1998 to 2001 was 37.6% for symptomatic (Centers for Disease Control and Prevention/modified and/or Paho/Caracas) and 9.7% for the Brazilian asymptomatic CD4 count <350 cells/mmAIDS-case definitions. Heterosexual/female patients were diagnosed earlier and presented the lowest case-fatality rate, followed by homosexual/male patients, heterosexual/male patients, and injecting drug users. In the multivariate Cox proportional hazards model, the period of diagnosis (hazard ratio = 2.66; 95% confidence interval [CI]: 2.58 to 2.74) and AIDS-case definition (hazard ratio = 4.48; 95% CI: 4.53 to 5.16) were strong predictors of survival. For the total AIDS cases, excluding death definition and undetermined exposure category, the estimated first quarter survival time improved from 4 months in 1992 to 1995 to 50 months in 1998 to 2001. Considering only the symptomatic AIDS-case definition, however, the improvement was from 4 months in the period 1992 to 1995 to 14 months in the period 1998 to 2001. The authors conclude that the survival improvement in Sao Paulo State was attributable to the introduction of anti-retroviral therapy with free universal access in 1996 and to earlier diagnosis associated with the introduction in 1998 of the Brazilian asymptomatic CD4 count <350 cells/mm AIDS-case definition with superior sensitivity compared with the symptomatic AIDS-case definitions.

Editors’ note: This study demonstrates on a population level the striking benefits of early diagnosis among asymptomatic patients and a higher CD4 count threshold at treatment initiation in a universal access programme.