Soledad García

Combined antiretroviral treatment and heterosexual transmission of HIV-1: cross sectional and prospective cohort study

Objective To estimate the risk and probability of heterosexual transmission of HIV-1 from infected people taking combined antiretroviral treatment. Design Cross sectional and prospective cohort studies. Setting HIV clinic in Madrid, Spain. Participants Stable heterosexual couples with one partner with HIV-1 infection (index partner) and the other reporting this sexual relationship as the only risk exposure. Main outcome measures HIV seroprevalence in non-index partners at enrolment and seroconversions in follow-up according to antiretroviral treatment taken by the index partner. Results In 476 couples in which the index partner was not taking antiretroviral treatment, HIV seroprevalence at enrolment in non-index partners was 9.2% (n=44), whereas in 149 couples in which the index partner was taking combined antiretroviral therapy no partner was infected (P<0.001). During follow-up, the 341 serodiscordant couples in which the index partner was not taking antiretroviral treatment had about 11 000 acts of intercourse without condoms, 50 natural pregnancies, and five HIV seroconversions (0.0004 per unprotected intercourse; 95% confidence interval 0.0001 to 0.0010); 294 of these couples always used condoms, accounting for about 42 000 acts of intercourse, 136 risk exposures from condom failure, and one HIV seroconversion. The relative risk associated with condom use was 0.07 (0.01 to 0.58). In 144 couples the index partner was taking combined antiretroviral treatment; they accounted for over 7000 unprotected acts of intercourse and 47 natural pregnancies but no HIV seroconversion (0 to 0.0005 per unprotected intercourse). Conclusions The heterosexual infectivity of HIV-1 in individuals taking effective antiretroviral treatment is low. Avoidance of unprotected intercourse and receipt of antiretroviral treatment by the infected partner in accordance with protocols are complementary measures to prevent HIV transmission.

Absence of hepatitis C virus transmission in a prospective cohort of heterosexual serodiscordant couples

Objective: To analyse hepatitis C virus (HCV) transmission in a cohort of heterosexual couples who are discordant both for HIV and for HCV. Methods: We followed an open cohort of 171 people, 152 women and 19 men, who were not initially infected by either HIV or HCV, and whose steady heterosexual partner presented antibodies to both viruses (index case). Other risk exposures were excluded. Every 6 months clinical, epidemiological, and risk behaviour information was collected, and antibodies to both viruses were determined. Results: During 529 person years of follow up more than 40 000 vaginal or anal penetrations were recorded. 74 partners (43.3%) had vaginal and/or anal intercourse without condoms with the index case; another 15.8%, who always used condoms, declared breaking or slipping episodes during intercourse; and another 22.2% had unprotected orogenital exposures. During the follow up, over 5800 unprotected vaginal and anal contacts with the index case were estimated, as well as more than 25 000 unprotected orogenital contacts. 31 women became pregnant (two were index cases), and seroconversion to HIV occurred for one woman (1.7 per 10 000 unprotected contacts; 95% CI, 0 to 9.5), but there was no seroconversion to HCV (95% CI, 0–6.3 per 10 000 unprotected contacts). Conclusion: These results are consistent with a low or null transmissibility of HCV in heterosexual relations, even when the index case is HIV co-infected.

Host and viral genetic correlates of clinical definitions of HIV-1 disease progression.

Background Various patterns of HIV-1 disease progression are described in clinical practice and in research. There is a need to assess the specificity of commonly used definitions of long term non-progressor (LTNP) elite controllers (LTNP-EC), viremic controllers (LTNP-VC), and viremic non controllers (LTNP-NC), as well as of chronic progressors (P) and rapid progressors (RP). Methodology and Principal Findings We re-evaluated the HIV-1 clinical definitions, summarized in Table 1, using the information provided by a selected number of host genetic markers and viral factors. There is a continuous decrease of protective factors and an accumulation of risk factors from LTNP-EC to RP. Statistical differences in frequency of protective HLA-B alleles (p-0.01), HLA-C rs9264942 (p-0.06), and protective CCR5/CCR2 haplotypes (p-0.02) across groups, and the presence of viruses with an ancestral genotype in the “viral dating” (i.e., nucleotide sequences with low viral divergence from the most recent common ancestor) support the differences among principal clinical groups of HIV-1 infected individuals. Conclusions A combination of host genetic and viral factors supports current clinical definitions that discriminate among patterns of HIV-1 progression. The study also emphasizes the need to apply a standardized and accepted set of clinical definitions for the purpose of disease stratification and research.

Evaluating the risk of HIV transmission through unprotected orogenital sex.

We analysed a cohort of heterosexual HIV- serodiscordant couples with the aim of evaluating the risk of transmission ascribed to unprotected orogenital intercourse. A total of 135 seronegative individuals (110 women and 25 men), whose only risk exposure to HIV was unprotected orogenital sex with their infected partner, registered 210 person-years of follow-up. After an estimated total of over 19,000 unprotected orogenital exposures with the infected partner not a single HIV seroconversion occurred.

Coinfection and Superinfection in Patients with Long-Term, Nonprogressive HIV-1 Disease

Human immunodeficiency virus 1 (HIV-1) dual infections are considered important because they have been related to AIDS progression. We identified dual infections in 2 patients with long-term, nonprogressive HIV-1 disease; the first patient was diagnosed as being already coinfected, on the basis of the first sample analyzed, but a previous superinfection could not be excluded; the second patient was diagnosed as having a superinfection, on the basis of the 9-year difference between the viral dating of the 2 strains. Dual infections occur in patients with long-term, nonprogressive disease, with no immediate clinical manifestations. Such occurrences could indicate a general phenomenon in natural HIV-1 infections.

Time trend in incidence of HIV seroconversion among homosexual men repeatedly tested in Madrid, 1988--2000.

An open cohort of 2670 homosexual men repeatedly tested for HIV at a Madrid clinic has registered 8050 person-years (PY) of follow-up and 157 seroconversions from 1988 to 2000. After declining from 1988 (4.71 per 100 PY), the incidence rate began a significant upward trend, reaching a figure of 2.16 per 100 PY in 2000. These findings ought to alert surveillance systems and prevention programmes.

Reducing sexual risk behavior among steady heterosexual serodiscordant couples in a testing and counseling program.

Objective: To assess the effect of an HIV counseling and testing program targeting steady heterosexual serodiscordant couples. Methods: We studied 564 couples who attended a sexually transmitted infections/HIV clinic in Madrid in the period 1989 to 2007 and participated in couples counseling and testing. Sociodemographic, epidemiologic, clinical, and behavioral information of both partners was obtained before testing the nonindex partner. Sexual practices reported in the first (preintervention) and second visit were compared, as well those reported in 4 additional visits. Results: Among the 399 couples who returned for a second visit (71%), the median number of sexual risk practices in the previous 6 months decreased (26.9–0; P <0.001) and the percentage of couples who had not engaged in sexual risk behavior increased (46.1–66.7; P <0.001). This reduction was maintained by the 143 couples who had 4 return visits. The diagnosis of HIV-infection in the index case previous to entering the program was associated with a lower frequency of sexual risk behavior. Independent predictors of postintervention risky sexual behavior included preintervention sexual risk behavior (odds ratio [OR]: 2.8, 95% confidence interval: 1.7–4.4), index case aged over 35 (OR: 2.0, 1.2–3.3), and a recent pregnancy (OR: 3.1, 1.6–6.3). The incidence of HIV seroconversion was 3.9 per 1000 couple-years (1.4–9.7). Conclusion: The diagnosis of HIV-infection and counseling appears to provide complementary reductions in sexual risk behaviors among serodiscordant steady heterosexual couples at follow-up, but the risk of transmission was not totally eliminated.

Factors influencing HIV progression in a seroconverter cohort in Madrid from 1985 to 1999

Objective: To study HIV progression from seroconversion over a 15 year period and measure the population effectiveness of highly active antiretroviral therapy (HAART). Methods: A cohort study of people with well documented dates of seroconversion. Cumulative risk of AIDS and death were calculated by extended Kaplan-Meier allowing for late entry. Cox proportional hazards models were used to study variables associated with HIV progression. To assess the impact of HAART, calendar time was divided in three periods; before 1992, 1992–6, and 1997–9. Results: From January 1985 to May 2000, 226 seroconverters were identified. The median seroconversion interval was 11 months, median seroconversion date was March 1993. 202 (89%) were men, 76% of whom were homo/bisexual. A 66% reduction in progression to AIDS was observed in 1997–9 compared to 1992–96 (HR 0.34 95% CI: 0.16 to 0.70). People with primary education appeared to have faster progression to AIDS compared to those with university studies (HR 2.69 95%CI: 1.17 to 6.16). An 82% reduction in mortality from HIV seroconversion was observed in 1997–9 (HR 0.18 95% CI: 0.05 to 0.68) compared to 1992–6. Progression to death for people with primary education was twice as fast as for those with university education (p 0.0007). People without confirmation of an HIV negative test had faster progression (HR 4.47 95% CI: 1.18 to 16.92). Conclusions: The reduction in progression to AIDS and death from seroconversion from 1992–6 to 1997–9 in Madrid is likely to be attributable to HAART. HIV progression was faster in subjects with primary education; better educational level may be associated with better adherence to medication.

Prevalencia de infección por el virus de la hepatitis B y necesidades de vacunación en colectivos de alto riesgo

Fundamento y objetivo Evaluar la situacion serologica del virus de la hepatitis B (VHB) y las necesidades de vacunacion en colectivos de alto riesgo. Pacientes y metodo Estudio transversal de personas atendidas en primera visita en un centro de diagnostico del virus de la inmunodeficiencia humana (VIH) de Madrid en el periodo 2000–2002. Los pacientes no vacunados contra el VHB se clasificaron segun sus marcadores serologicos en: infeccion activa (HBsAg+), infeccion pasada (anti-HBc+ y HBsAg–) y susceptibles (anti-HBc–). Resultados Se estudio a 7.827 pacientes, un 5,2% eran usuarios de drogas por via parenteral, un 21% eran varones homosexuales, un 38% eran mujeres que ejercian la prostitucion y el 34% tenia otras exposiciones heterosexuales. El 50% eran extranjeros. La prevalencia del VIH fue del 4,1%. El 10,4% habia iniciado o completado la vacunacion. La prevalencia de HBsAg+ fue del 1,2%, asociandose a edad mayor de 30 anos y al origen en Africa o Europa del Este. El 76% era susceptible al VHB, situacion que se asocio independientemente a ser varon, menor de 30 anos, riesgo heterosexual, origen espanol o latinoamericano y no infectado por el VIH. Conclusiones Se requiere intensificar la vacunacion en los dispositivos asistenciales que atienden a colectivos de alto riesgo.

Genetic analysis of HIV-1 samples from Spain.

Summary: To characterize the viruses responsible for the HIV‐1 epidemic in Spain, we genetically characterized 79 samples obtained from Spanish patients with different risk practices (injecting drug users and male homosexuals) in two regions (Madrid and Navarra). Genetic characterization was carried out by nucleotide sequencing in the C2‐V3‐C3 region and by phylogenetic analysis. All samples were of subtype B except one that clustered with clade F. Because no segregation of samples was determined according to the risk group of patients nor to their geographic origin, the Spanish samples analyzed constitute a single group of viruses. These data, along with the starlike topology of the phylogenetic tree, support the existence of a single introduction of HIV‐1 subtype B in Spain. The mean genetic distance among subtype B sequences was of 13.9% ± 0.06% (range, 5%‐25%), suggesting an epidemic of long evolution. Analysis of sequences in relation to isolation dates revealed an increase in the heterogeneity of the nucleotide sequences with time. According to these data, a divergence rate of 0.49% ± 0.11% per year was calculated for the Spanish samples during the period analyzed.