Conflicting data on the role of total virus- and protein-specific cytotoxic-T-lymphocyte (CTL) responses in the control of human immunodeficiency virus (HIV) disease progression exist. We present data generated from a Peruvian cohort of untreated, clade B-infected subjects, demonstrating that the proportion of Gag-specific, and in particular p24-reactive, CTL responses among the total virus-specific CTL activity is associated with individuals' CD4 counts and viral loads. Analyses in a second cohort in the United States confirm these findings and point towards a dominant role of Gag-specific immunity in effective control of HIV infection, providing important guidance for HIV vaccine development.

Background. Herpes simplex virus type 2 (HSV-2) infection is common among human immunodeficiency virus (HIV)-infected persons, and HSV reactivation increases plasma and genital HIV-1 levels. We studied HIV-1 levels during HSV suppression in coinfected persons in a placebo-controlled crossover trial.Methods. Twenty antiretroviral therapy (ART)-naive HIV-1/HSV-2-seropositive men who have sex with men in Lima, Peru, with CD4 cell counts Ͼ200 cells/L were randomized to receive either valacyclovir at 500 mg twice daily or placebo for 8 weeks, after which they underwent a 2-week washout period and then received the alternative regimen for 8 weeks. Specimens included daily anogenital swabs (for HSV DNA polymerase chain reaction [PCR]), thrice weekly rectal mucosal secretions (for HIV-1 RNA and HSV DNA PCR) obtained by anoscopy, and weekly plasma (for HIV-1 RNA PCR). Outcomes were rectal and plasma HIV-1 RNA levels by treatment arm.Results. HIV-1 was detected in 73% of 844 rectal and 99% of 288 plasma specimens. HSV was detected in 29% and 4% of mucocutaneous specimens obtained during placebo and valacyclovir administration, respectively (P Ͻ .001). Valacyclovir resulted in a 0.16 (95% confidence interval [CI], 0.07-0.25; P ϭ .0008; 33% decrease) log 10 copies/mL lower mean within-subject rectal HIV-1 level and a 0.33 (95% CI, 0.23-0.42; P Ͻ .0001; 53% decrease) log 10 copies/mL lower plasma HIV-1 level, compared with values for placebo.Conclusions. Valacyclovir significantly reduces rectal and plasma HIV-1 levels in HIV-1/HSV-2-coinfected men. HSV suppression may provide clinical benefits to persons not receiving highly active ART as well as public health benefits.Trial registration. ClinicalTrials.gov identifier: NCT00378976.

A randomized cross-over trial of HSV-2 suppressive therapy was conducted among 20 HSV-2/HIV-1 co-infected Peruvian women not on antiretroviral therapy. Participants were assigned valacyclovir 500 mg twice daily or placebo for 8 weeks, then after a 2 week washout, the alternative for 8 weeks. Plasma (weekly) and endocervical swabs (thrice weekly) were collected for HIV-1 RNA PCR. HIV-1 plasma levels were significantly lower during the valacyclovir arm compared with the placebo arm (−0.27 log10 copies/ml, p<0.001, a 46% decrease), as were cervical HIV-1 levels (−0.35 log10 copies/swab, p<0.001, a 55% decrease). Suppressive HSV-2 therapy could reduce HIV-1 infectiousness and slow HIV-1 disease progression. (ClinicalTrials.gov number NCT00465205).

HIV continued to spread among MSM in Lima even when a decline in bacterial STIs and increase in condom use were estimated to occur. Intensification of medical and behavior prevention interventions is warranted for MSM in Peru.

We found a strong association between HSV-2 seropositivity and HIV infection. Intervention measures against GUD due to HSV-2 infection and syphilis, such as routine testing, early detection, HSV-2 suppressive treatment, and condom distribution, need to be enhanced as part of STI prevention strategies at a national level to effectively reduce HIV infection among MSM in Peru.

Background In the Andean Region, HIV and sexually transmitted infections (STI) are most prevalent among men who have sex with men (MSM), but incidence estimates and associated factors have never been prospectively assessed. Methods A cohort of 1056 high-risk HIV-negative MSM in Lima, Peru, was recruited during 1998–2000 (The ALASKA Cohort) and a nested case-control analysis conducted between seroconverters and non-seroconverters, matched 1:3 by age and duration of follow-up for comparison of risk behaviors, acute retroviral symptoms, circumcision, and STI. Results During average follow-up of 335 days, 34 men seroconverted, providing a HIV incidence estimate of 3.5/100 person-years (95% CI: 2.3–4.7). High syphilis (9.2/100 person-years, 95% CI: 6.7–10.1) and HSV-2 infection (10.4/100 person-years, 95% CI: 8.6–11.9) incidence estimates were obtained. HIV seroconverters were more likely than men who remained seronegative to report fever ≥3 days (46% vs. 7%), to seek medical care (62% vs. 27%), and to have ≥1 casual partner (86.2% vs. 74.1%) since their last visit. HIV seroconverters also were more likely to have acquired syphilis or HSV-2 infection (31% vs. 8% among initially HSV-2 seronegative men) while were less likely to be circumcised (4.2% vs. 20.6%, a non-significant difference). In multivariate analysis, incident syphilis or HSV-2 infection (OR: 5.9, 95% CI 1.5–22.7) and sex with any casual partner (OR: 4.8, 95% CI: 0.9–26.2) were associated with HIV seroconversion. Conclusions STI that may cause anogenital ulcers are important risk factors for HIV acquisition among high-risk MSM in Lima, a population with a very high HIV incidence estimate. Synergistic interventions focusing in preventing both HIV and HSV-2, like male circumcision, are warranted to be assessed, especially in MSM populations with low levels of circumcision and high incidence estimates of ulcerative STI.

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High levels of human immunodeficiency virus (HIV) in rectal secretions and semen likely increase the risk of HIV transmission. HIV-infected men who have sex with men made 2-3 study visits, over 4 weeks, to assess rectal, seminal, and plasma levels of HIV RNA. Mixed-effects models estimated the effect of factors on HIV shedding. Twenty-seven (42%) of 64 men were receiving antiretroviral therapy (ART); regardless of ART use, median HIV RNA levels were higher in rectal secretions (4.96 log(10) copies/mL) than in blood plasma (4.24 log(10) copies/mL) or seminal plasma (3.55 log(10) copies/mL; P<.05, each comparison). ART was associated with a 1.3-log(10) reduction in rectal HIV RNA in a model without plasma HIV RNA; with and without plasma RNA in models, ART accounted for a >1-log(10) decrease in seminal HIV RNA levels. Thus, controlling for plasma HIV RNA, ART had an independent effect on seminal, but not rectal, HIV levels.