Progression to AIDS and death and response to HAART in men and women from a multicenter hospital-based cohort.

OBJECTIVE: To study if progression to AIDS and death, as well as clinical and virological response to highly active antiretroviral therapy (HAART), differs between men and women. METHODS: We studied a multicenter, hospital-based cohort of HIV-infected patients attending 10 hospitals in Spain from January 1997 to December 2003. Kaplan-Meier and Cox regression were used to assess the effect of sex on time to AIDS, survival from AIDS, onset of a new AIDS event or death, and viral suppression from HAART. RESULTS: Of 4643 patients, 27% were women. Women had statistically significant lower viral loads (VL) of 3.9 vs. 4.1 log10/mL (p = 0.02) and higher median CD4 counts of 339 vs. 288 cells/mm3 (p < 0.001) at entry and were more likely to be AIDS free at entry. In univariate analysis, women seemed to show a nonsignificant lower progression to AIDS (HR 0.88) (95 CI% 0.73-1.07), which disappeared in multivariate analyses (HR 1.03) (95% CI 0.82-1.29). Survival from AIDS seemed to be higher in women (HR 0.65) (95% CI 0.40-1.05), but differences became clearly nonsignificant after adjustments (HR 0.71) (95% CI 0.42-1.23). No differences were seen in time to new AIDS condition or death after HAART (HR 1.08) (95% CI 0.80-1.46) in multivariate analyses. No differences were seen for time to VL suppression after initiation of HAART (HR 1.07) (95% CI 0.92-1.24). CONCLUSIONS: We have found no differences in HIV progression and response to HAART attributable to gender among patients accessing the Spanish hospital network.

Delay in the initiation of HAART, poorer virological response, and higher mortality among HIV-infected injecting drug users in Spain.

Differences in the uptake and time to initiation of highly active antiretroviral therapy (HAART), the virological response to HAART, and survival from AIDS by transmission category were analyzed. A multicenter hospital-based cohort of HIV-infected patients attending 10 hospitals in Spain from January 1997 to December 2003 was used. Cross-checks with the National AIDS Registry were performed. Cox proportional hazard models were used to assess the impact of transmission category on time to HAART initiation, viral suppression (defined by first HIV-1 RNA viral load measurement <500 copies/ml after HAART), and survival from AIDS. Of 4643 patients, 73% were men and 56% were injecting drug users (IDUs). A statistically significant interaction was found between transmission category and previous non-HAART antiretroviral treatment (ART) (p < 0.05). Among ART naive patients, IDUs had a 33% lower risk of initiating HAART compared to men who have sex with men (MSM) [HR 0.67 (95% CI 0.57-0.79)]. No differences by transmission categories were seen among patients with prior non-HAART ART. IDUs had poorer viral load (VL) suppression than MSM [HR 0.86 (95% CI 0.74-0.99)] adjusting by baseline VL, AIDS diagnosis, and prior ART. Mortality from AIDS was two and a half times higher in IDUs than MSM [HR 2.51 (95% CI 1.03-6.1)]. Among patients who access the hospital network, IDUs have a lower uptake of HAART, have worse virological suppression, and have higher mortality after AIDS diagnosis. There is a need to extend the programs in order to enhance access and adherence of IDUs to HAART and consider the treatment of drug addiction as an integral part of the treatment for HIV infection.

Rate, causes, and clinical implications of presenting with low CD4+ cell counts in the era of highly active antiretroviral therapy.

Of patients attending HIV clinics, neither the proportion with CD4(+) cell counts below 200 cells/microl, and therefore at risk for developing opportunistic infections (OIs), nor the reasons for the persistence of low CD4(+) cell counts are well known in the era of highly active antiretroviral therapy (HAART). In an effort to gather data concerning this issue, the charts of all outpatients who attended two reference HIV clinics in Spain throughout the year 2001 were retrospectively reviewed. Of 1897 subjects, 213 (11%) had at least one CD4(+) cell count determination below 200 cells/microl during 2001. The main reasons for presenting with low CD4(+) cell counts were as follows: (1) poor treatment adherence, 64 (30%); (2) poor immune recovery despite complete virus suppression for longer than 1 year on HAART, 47 (22%); (3) virologic failure under HAART, 33 (15%); (4) no antiretroviral therapy, 23 (11%); (5) initiation of HAART within the current year in subjects with very low CD4(+) cell counts, 17 (8%); (6) impediment in using HAART due to toxicity, 17 (8%); and (7) drug-induced myelotoxicity, 12 (6%). During the period under review, one or more OIs developed in 52 of the 213 (24%) patients with low CD4(+) cell counts. They occurred more frequently in subjects who were naive for antiretroviral drugs or who initiated therapy recently (RR, 6.45; 95% CI, 2.43-17.12; p < 0.001), and conversely tended to be less frequent among subjects with poor immune reconstitution despite complete virologic suppression while on HAART (RR 0.86; 95% CI, 0.28-2.62; p = 0.79). A lower lifetime CD4(+) cell count nadir was associated with a greater risk of developing an OI (RR, 0.98; 95% CI, 0.97-0.99; p < 0.001). We conclude that, despite the availability of HAART, more than 10% of patients currently attending HIV clinics have CD4(+) cell counts <200 cells/microl, and continue to be at risk for developing OIs. Poor treatment adherence and lack of immune recovery despite complete virus suppression while on HAART account for more than half of cases.

Natural pregnancies in HIV-serodiscordant couples receiving successful antiretroviral therapy.

Increasing numbers of HIV-serodiscordant heterosexual couples are concerned about the chances for pregnancy. We reviewed all natural pregnancies attained by HIV-serodiscordant couples seen in 3 clinics in Spain, in which the infected partner had undetectable plasma viremia while receiving highly active antiretroviral therapy (HAART). In the case of HIV-infected mothers, only those with undetectable viremia during pregnancy and at delivery were chosen. A total of 62 HIV-serodiscordant couples, 22 HIV-infected women (mean CD4 count of 522 cells/microL, 55% hepatitis C virus [HCV]-seropositive) and 40 HIV-infected men (mean CD4 count of 629 cells/microL, 75% HCV-seropositive), were recorded. Overall, 76 natural pregnancies occurred, and 68 children were born. There were 9 fetal deaths, 1 twin pregnancy, 6 couples with 2 consecutive babies, and 4 couples with 3 consecutive newborns. There were no cases of HIV seroconversion in uninfected sexual partners. One case of vertical HIV transmission occurred, however. Serodiscordant couples attaining natural pregnancy are exposed to a negligible risk of sexual transmission of HIV when the infected partner presents with complete suppression of plasma viremia while receiving HAART.