Neutralization Susceptibility of B Subtype Variant B' Primary HIV-1 Isolates

Susceptibility to autologous and heterologous neutralization of primary human immunodeficiency virus (HIV)-1 isolates belonging to subtype B, to the B'-variant of subtype B or to subtype F from infected individuals residing in Rio de Janeiro was assayed. A lower infectivity of the B'- and F isolates when compared to the classical B-subtype HIV-1 isolates was observed. Comparisons of neutralization susceptibilities were carried out for 19 B-subtype, 11 B'-variant and two F-subtype HIV-1 isolates with plasma from autologous and heterologous samples. Frequency of autologous neutralization was slightly lower for B-subtype isolates in comparison to B'-variant isolates. Heterologous intra-subtype neutralization was significantly lower for B-subtype than for the B'-variant or the F-subtype isolates. While B-subtype isolates were neutralized by most anti-F-subtype plasma, F-subtype isolates, although most susceptible to F-subtype antibodies, were highly susceptible to neutralization by anti-B-subtype antibodies. Cross-neutralization for B'-variant and B-subtype isolates was not as extensive as observed for B- and F-subtype isolates. However, the results presented indicate a quite extensive cross-neutralization between Brazilian HIV-1 isolates.     

Vertical HIV-1 transmission: importance of neutralizing antibody titer and specificity

Neutralization analyses were carried out with plasma from 132 volunteer human immunodeficiency virus (HIV)-1 infected women (76% pregnant, 24% with infants suspected for HIV-1 infection) collected between 1994 and 1998, against autologous and heterologous primary- and the reference HIV-1 MN isolates. A significantly lower percentage of HIV-1 transmissions was observed after 1996, parallel to a more intense antiretroviral treatment of infected pregnant women. HIV-1 isolation was significantly more frequent from peripheral blood mononuclear cells of mothers of infected children than mothers of uninfected children (P = 0.0065). Neutralization of autologous HIV-1 isolates was comparable for HIV-1 transmitters and nontransmitters' plasma, whereas neutralization of the reference isolate HIV-1 MN was more frequent at high titers for pregnant women who did not transmit HIV to their offspring compared to pregnant women who did. Although neutralization of heterologous primary HIV-1 isolates from HIV transmitters and non transmitters by transmitter plasma occurred with similar frequency, neutralization of isolates from transmitters was much more frequent when heterologous plasma from nontransmitters were used. Macrophage-tropic heterologous HIV-1 isolates were neutralized more frequently at higher titers by plasma from nontransmitters than from transmitters. The results obtained indicate that antiretroviral treatment, lack of success of HIV-1 isolation and high titers of antibodies able to neutralize macrophage-tropic viruses appear to be of importance for protection against HIV-1 vertical transmission for the group of patients studied.     

Barriers and facilitators to PrEP for transwomen in Brazil

Pre-exposure prophylaxis (PrEP) is an important biomedical intervention that may help reduce the risk of HIV transmission among transwomen. To date, little research is available to inform interventions to increase uptake and adherence to PrEP among transwomen, especially in places outside the U.S. We conducted a qualitative study in 2015 with 34 adult transwomen in Rio de Janeiro, Brazil and assessed awareness, interest, barriers and facilitators to PrEP uptake and adherence for transwomen. Almost one third of participants had heard of PrEP, and most were interested and thought it would be beneficial for transwomen in their community. Barriers to PrEP included fear of being HIV positive resulting in low HIV testing and concerns about the ability to adhere to a daily PrEP regimen. The most prominent barrier to uptake was past experiences of transgender-identity related discrimination in the universal health care system that reduced willingness to seek PrEP or health care in general. Participants recommended technological solutions to PrEP health education information that could address uptake and adherence. This study informs efforts to increase PrEP use among transwomen in Brazil.     

Optimising HIV programming for transgender women in Brazil

In Brazil, little data is available to inform HIV prevention programming for travestis and transgender (‘trans’) women, despite the existence of a social movement that has gained strength in recent years. We conducted formative research in Rio de Janeiro to gather trans women’s perspectives on combination HIV prevention approaches. Framing the analysis within the model of gender affirmation, we found that several social and contextual factors inhibited participants’ access to HIV prevention and treatment. Experienced and anticipated gender-related discrimination and HIV stigma were linked to the avoidance of HIV testing, health services and HIV status disclosure. Participants recommended HIV prevention interventions which combined socio-structural interventions, such as peer-based empowerment and social support, with biomedical interventions such as pre-exposure prophylaxis (PrEP). Participants expressed a preference for programmes and interventions that emphasised a gender-affirmative approach, promoted autonomy and aimed to reduce stigma and discrimination in public health services.     

Emulating a trial of joint dynamic strategies: An application to monitoring and treatment of HIV-positive individuals

Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen? We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the “no direct effect” assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/μl compared with 500 cells/μl and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The “no direct effect” assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size.     

Analysis of serious non‐AIDS events among HIV‐infected adults at Latin American sites

Objective

Acquired immune deficiency appears to be associated with serious non‐AIDS (SNA)‐defining conditions such as cardiovascular disease, liver and renal insufficiency and non‐AIDS‐related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort.

Materials and methods

Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV‐associated factors on non‐AIDS‐defining conditions.

Results

Among 6007 patients in follow‐up, 130 had an SNA event (0.86 events/100 person‐years of follow‐up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non‐AIDS‐defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T‐cell count prior to index date (P=0.0056, with an average difference of more than 100 cells/μL) and area under the CD4 cell curve in the year previous to index date (P=0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors.

Conclusions

The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.